ORCID Profile
0000-0002-5554-6946
Current Organisation
Royal Brisbane and Women's Hospital
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Publisher: Cambridge University Press (CUP)
Date: 21-10-2015
DOI: 10.1016/J.EURPSY.2015.09.009
Abstract: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate ( P = . 032) and earlier occurrence ( P = .043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large s le.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
DOI: 10.1038/S41398-020-0787-9
Abstract: Depression is a leading cause of burden of disease among young people. Current treatments are not uniformly effective, in part due to the heterogeneous nature of major depressive disorder (MDD). Refining MDD into more homogeneous subtypes is an important step towards identifying underlying pathophysiological mechanisms and improving treatment of young people. In adults, symptom-based subtypes of depression identified using data-driven methods mainly differed in patterns of neurovegetative symptoms (sleep and appetite/weight). These subtypes have been associated with differential biological mechanisms, including immuno-metabolic markers, genetics and brain alterations (mainly in the ventral striatum, medial orbitofrontal cortex, insular cortex, anterior cingulate cortex amygdala and hippoc us). K -means clustering was applied to in idual depressive symptoms from the Quick Inventory of Depressive Symptoms (QIDS) in 275 young people (15–25 years old) with MDD to identify symptom-based subtypes, and in 244 young people from an independent dataset (a subs le of the STAR*D dataset). Cortical surface area and thickness and subcortical volume were compared between the subtypes and 100 healthy controls using structural MRI. Three subtypes were identified in the discovery dataset and replicated in the independent dataset severe depression with increased appetite, severe depression with decreased appetite and severe insomnia, and moderate depression. The severe increased appetite subtype showed lower surface area in the anterior insula compared to both healthy controls. Our findings in young people replicate the previously identified symptom-based depression subtypes in adults. The structural alterations of the anterior insular cortex add to the existing evidence of different pathophysiological mechanisms involved in this subtype.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2015
Publisher: Informa Healthcare
Date: 18-10-2010
DOI: 10.1517/14728222.2010.528394
Abstract: Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed. Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews. This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder. Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.
Publisher: Bentham Science Publishers Ltd.
Date: 15-05-2015
DOI: 10.2174/157488631002150515120209
Abstract: The efficacy of clozapine for the treatment of schizophrenia has been demonstrated. However, a range of adverse events have been associated with its use. To date, there remains a paucity of data regarding the prevalence of clozapine-induced cardiovascular (CV) and parameters associated with the development of metabolic syndrome, alongside associated risk factors for their development. An observational, clinical cohort study design of 355 clozapine patients who were enrolled in the Barwon Health Clozapine Program at Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were accessed retrospectively. Multivariate logistic regression was used to determine associations with adverse event(s). Older age of commencement with clozapine was consistently associated with increased risk of CV abnormalities, with the exception of tachycardia where older age was protective (Odds Ratio [OR]: 0.97 95% Confidence Intervals [CI]: 0.95, 0.99). Males had significantly greater odds of most metabolic disturbances with the exception of being obese (BMI: ≥30 OR: 0.45 95% CIs: 0.24, 0.85). Older age of commencement was a significantly associated variable with High- Density Lipoprotein-cholesterol (OR: 1.03 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04 95% CIs: 1.02, 1.07). An increase in BMI was consistently and significantly associated with all metabolic events. Male patients who are obese at any point during treatment and older at treatment commencement may be the most vulnerable to adverse CV and metabolic events. While future studies using a matched case-control design may be required to verify these findings, we recommend that treating clinicians consider these risks when assessing patient suitability to clozapine therapy.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.NEUBIOREV.2012.06.001
Abstract: Deep brain stimulation (DBS), a neuromodulation therapy that has been used successfully in the treatment of symptoms associated with movement disorders, has recently undergone clinical trials for in iduals suffering from treatment-resistant depression (TRD). Although the small patient numbers and open label study design limit our ability to identify optimum targets and make definitive conclusions about treatment efficacy, a review of the published research demonstrates significant reductions in depressive symptomatology and high rates of remission in a severely treatment-resistant patient group. Despite these encouraging results, an incomplete understanding of the mechanisms of action underlying the therapeutic effects of DBS for TRD is highlighted, paralleling the incomplete understanding of the neuroanatomy of mood regulation and treatment resistance. Proposed mechanisms of action include short and long-term local effects of stimulation at the neuronal level, to modulation of neural network activity.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.BIOPSYCH.2021.09.008
Abstract: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and erse international s le with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippoc al cortex (0.18 <d < 0.22). More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex. In the hitherto largest longitudinal MRI study on BD, we did not detect accelerated cortical thinning but noted faster ventricular enlargements in BD. However, abnormal frontocortical thinning was observed in association with frequent manic episodes. Our study yields insights into disease progression in BD and highlights the importance of mania prevention in BD treatment.
Publisher: Cambridge University Press (CUP)
Date: 12-2007
Publisher: Cambridge University Press (CUP)
Date: 04-2010
DOI: 10.1111/J.1601-5215.2010.00452.X
Abstract: Gomes FA, Kauer-Sant’Anna M, Magalhães PV, Jacka FN, Dodd S, Gama CS, Cunha Â, Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in bipolar disorder. There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder. Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese. Over 30% of the s le was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03) as likely to have a history of suicide attempt(s). Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.SCHRES.2017.04.036
Abstract: Psychosis and mania share conceptual, genetic and clinical features, which suggest the possibility that they have common antecedents. Participants identified to be at-risk for psychosis might also be at-risk for mania. We aimed to identify the rate and predictors of transition to mania in a cohort of youth with clinical or familial risk for psychosis. Among a cohort of 416 young people with an at-risk mental state for psychosis defined using the Ultra-High-Risk (UHR) criteria, 74.7% were followed up between 5 and 13years from their baseline assessment. We undertook a matched case-control examination of those who developed mania over the follow-up period compared to those who did not develop mania or psychosis. Transition to mania was determined using either a structured clinical interview, or diagnoses from a state-wide public mental health contact registry. Clinical characteristics and risk factors were examined at baseline using information from structured interviews, clinical file notes, rating scales and unstructured assessments. Eighteen participants developed mania (UHR-Manic transition or UHR-M, 4.3%). In comparison with participants matched on age, gender and baseline-study who developed neither mania nor psychosis, more UHR-M participants had subthreshold manic symptoms or were prescribed antidepressants at baseline. They also had lower global functioning. In addition to the UHR criteria, features such as subthreshold manic symptoms and antidepressant use may help identify at-risk groups that predict the onset of mania in addition to transition to psychosis. Presence of manic symptoms may also indicate syndrome specificity early in the prodromal phase.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JAD.2014.11.030
Abstract: Type 2 diabetes and depression are commonly comorbid high-prevalence chronic disorders. Diet is a key diabetes risk factor and recent research has highlighted the relevance of diet as a possible risk for factor common mental disorders. This study aimed to investigate the interrelationship among dietary patterns, diabetes and depression. Data were integrated from the National Health and Nutrition Examination Study (2009-2010) for adults aged 18+ (n=4588, Mean age=43yr). Depressive symptoms were measured by the Patient Health Questionnaire-9 and diabetes status determined via self-report, usage of diabetic medication and/or fasting glucose levels ≥126mg/dL and a glycated hemoglobin level ≥6.5% (48mmol/mol). A 24-h dietary recall interview was given to determine intakes. Multiple logistic regression was employed, with depression the outcome, and dietary patterns and diabetes the predictors. Covariates included gender, age, marital status, education, race, adult food insecurity level, ratio of family income to poverty, and serum C-reactive protein. Exploratory factor analysis revealed five dietary patterns (healthy unhealthy sweets 'Mexican' style breakfast) explaining 39.8% of the total variance. The healthy dietary pattern was associated with reduced odds of depression for those with diabetes (OR 0.68, 95% CI [0.52, 0.88], p=0.006) and those without diabetes (OR 0.79, 95% CI [0.64, 0.97], p=0.029) (interaction p=0.048). The relationship between the sweets dietary pattern and depression was fully explained by diabetes status. In this study, a healthy dietary pattern was associated with a reduced likelihood of depressive symptoms, especially for those with Type 2 diabetes.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JAD.2022.05.076
Abstract: Network analysis provides opportunities to gain a greater understanding of the complex interplay of risk factors for depression and heterogeneous symptom presentations. This study used network analysis to discover risk factors associated with both depression severity and depression symptoms amongst Pacific adolescents in New Zealand. Mixed graphical models with regularization were fitted to data from a community s le of New Zealand born, Pacific adolescents, (n = 561 51% male Mean age (SD) = 17 (0.35)) and associations between a wide range of potentially explanatory variables and depression severity and depression symptoms investigated. The associations identified were then tested for reliability, using res ling techniques and sensitivity analysis. In the networks, the explanatory variables associated with both depression severity and depression symptoms were those related to quality of the relationships with mother or friends, school connectedness, and self-assessed weight, but the symptoms they were associated with varied substantially. In the depression severity networks, impulsivity appeared to be a bridging node connecting depression severity with delinquency and negative peer influence. The data were analysed cross-sectionally, so causal inferences about the directions of relationships could not be inferred and most of the data were self-reported. The results illustrate the varied way that adolescent depression can manifest itself in terms of symptoms and suggest specific items on the depression inventory that might be suitable targets for prevention strategies and interventions, based on the risk factor - depression symptom profiles of in iduals or groups.
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Springer Science and Business Media LLC
Date: 03-03-2023
Publisher: Springer Science and Business Media LLC
Date: 28-10-2014
DOI: 10.1038/MP.2014.139
Abstract: There is currently considerable imprecision in the nosology of biomarkers used in the study of neuropsychiatric disease. The neuropsychiatric field lags behind others such as oncology, wherein, rather than using 'biomarker' as a blanket term for a erse range of clinical phenomena, biomarkers have been actively classified into separate categories, including prognostic and predictive tests. A similar taxonomy is proposed for neuropsychiatric diseases in which the core biology remains relatively unknown. This paper ides potential biomarkers into those of (1) risk, (2) diagnosis/trait, (3) state or acuity, (4) stage, (5) treatment response and (6) prognosis, and provides illustrative exemplars. Of course, biomarkers rely on available technology and, as we learn more about the neurobiological correlates of neuropsychiatric disorders, we will realize that the classification of biomarkers across these six categories can change, and some markers may fit into more than one category.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Informa UK Limited
Date: 25-03-2019
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.SLEEP.2013.11.783
Abstract: Excessive daytime sleepiness (EDS) is associated with significant personal and medical burden. However, there is little indication of the impact of these symptoms in the broader population. We studied 946 men ages 24-92 years (median age, 59.4 [interquartile range {IQR}, 45-73 years]) and 1104 women ages 20-94 years (median age, 50 [IQR, 34-65 years]) who resided in the Barwon Statistical Division, South-Eastern Australia, and participated in the Geelong Osteoporosis Study (GOS) between the years of 2001 and 2008. EDS was defined as an Epworth Sleepiness Scale (ESS) score of ⩾ 10. Lifestyle factors, history of medical conditions, and medication history were documented by self-report. For men, the age-specific prevalence of EDS was 5.1% (ages 20-29 years), 6.4% (ages 30-39 years), 9.8% (ages 40-49 years), 15.5% (ages 50-59 years), 12.0% (ages 60-69 years), 12.0% (ages 70-79 years), and 29.0% (ages ⩾ 80 years). For women, the age-specific prevalence of EDS was 14.7% (ages 20-29 years), 8.7% (ages 30-39 years), 15.0% (ages 40-49 years), 16.0% (ages 50-59 years), 12.6% (ages 60-69 years), 13.2% (ages 70-79 years), and 17.0% (ages ⩾ 80 years). Overall standardized prevalence of EDS was 10.4% (95% confidence interval, 9.7-11.2) for men and 13.6% (95% confidence interval, 12.8-14.4) for women. The prevalence of EDS increased with age, affecting approximately one-third of those aged ⩾ 80 years. Because EDS has been associated with poorer health outcomes in the older age strata, these findings suggest that routine screening may be beneficial in ongoing health assessments for these in iduals. Overall, more than one-tenth of the Australian adult population has EDS, which is indicative of possible underlying sleep pathology.
Publisher: Bentham Science Publishers Ltd.
Date: 02-2012
DOI: 10.2174/138161212799316226
Abstract: Bipolar affective disorder (BD) is a severe, recurrent and disabling disorder with devastating consequences for in iduals, families and society. Although these hazards and costs provide a compelling rationale for development of early detection and early intervention strategies in BD, the development of at-risk criteria for first episode mania is still in an early stage of development. In this paper we review the literature with respect to the clinical, neuroantomical and neuropsychological data, which support this goal. We also describe our recently developed bipolar at-risk criteria (BAR). This criteria comprises the peak age range of the first onset of bipolar disorder, genetic risk, presenting with sub-threshold mania, cyclothymic features or depressive symptoms. An initial pilot evaluation of the BAR criteria in 22 subjects indicated conversion rates to proxies of first-episode mania of 23% within 265 days on average, and high specificity and sensitivity of the criteria. If prospective studies confirm the validity of the BAR criteria, then the criteria would have the potential to open up new avenues of research for indicated prevention in BD and might therefore offer opportunities to ameliorate the severity of, or even prevent BD.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2021
Publisher: Springer Science and Business Media LLC
Date: 08-11-2022
DOI: 10.1186/S12872-022-02921-1
Abstract: Studies suggest increased risk for an outcome in people with joint exposures that share common causal pathways. The objective of this study was to determine the risk of incident acute myocardial infarction (AMI) following exposure to both albuminuria and/or anxiety and depression symptoms. Participants who provided urine s les to the HUNT2 (1995–97) or HUNT3 (2007–2009) surveys were followed until the end of 2016. Albuminuria was measured by Albumin Creatine Ratio (ACR) and participants self-reported mood and anxiety symptoms on the Hospital Anxiety and Depression scale. We used Cox regression to estimate hazard ratios (HRs) for first incident AMI considering interaction between exposures and additive models to calculate the proportion of AMI that were attributable to the synergy of both exposures, adjusted for the Framingham variables. Eleven thousand fourteen participants free of previous AMI were eligible for participation, with 1234 incident AMIs occurred during a mean 13.7 years of follow-up. For participants who had a healthier CVD risk profile, the HR for AMI of having both albuminuria (3–30 mg/mmol) and depression (≥8) was 2.62 (95% 1.12–6.05) compared with a HR 1.34 (95% CI 1.04–1.74) with raised ACR only (Likelihood Ratio-test 0.03). Adding anxiety (≥8) to albuminuria (3–30) tripled the risk (HR 3.32 95% CI 1.43–7.17). The additive models suggest that these risks are not higher than expected based on each risk factor alone. This study indicate that the risk of AMI in persons with elevated albuminuria but with an otherwise healthy CVD profile might be lified by anxiety and depression symptoms. The increased risk with joint risk factors is not higher than expected based on each risk factor alone, which indicate that the risk factors do not share causal pathways.
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.BIOPSYCH.2021.10.021
Abstract: Major depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder, but little is known about the genetic characterization of this heterogeneity. Understanding the genetic etiology of MDD can be challenging because large s le sizes are needed for gene discovery-often achieved with a trade-off in the depth of phenotyping. The Australian Genetics of Depression Study is the largest stand-alone depression cohort with both genetic data and in-depth phenotyping and comprises a total of 15,792 participants of European ancestry, 92% of whom met diagnostic criteria for MDD. We leveraged the unique nature of this cohort to conduct a meta-analysis with the largest publicly available depression genome-wide association study to date and subsequently used polygenic scores to investigate genetic heterogeneity across various clinical subtypes of MDD. We increased the number of known genome-wide significant variants associated with depression from 103 to 126 and found evidence of association of novel genes implicated in neuronal development. We found that a polygenic score for depression explained 5.7% of variance in MDD liability in our s le. Finally, we found strong support for genetic heterogeneity in depression with differential associations of multiple psychiatric and comorbid traits with age of onset, longitudinal course, and various subtypes of MDD. Until now, this degree of detailed phenotyping in such a large s le of MDD cases has not been possible. Along with the discovery of novel loci, we provide support for differential pathways to illness models that recognize the overlap with other common psychiatric disorders as well as pathophysiological differences.
Publisher: SAGE Publications
Date: 22-10-2020
Abstract: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. A total of 112 participants were included in the pooled data (Dean et al., n = 71 Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen’s D (95% confidence interval): 0.71 [0.29, 1.14], p 0.001 – anxiety severity – differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen’s D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status – differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen’s D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator redictor. The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.JPSYCHORES.2006.12.009
Abstract: This article reviews recent studies relating to the impact of depression and its treatment on the health-related quality of life (HRQOL) of patients with coronary artery disease (CAD). Articles for the primary review were identified via MEDLINE and PsycINFO (1995-2006). Evidence suggests that depression has an aversive impact on the HRQOL of patients with stable CAD as well as on patients hospitalized for acute myocardial infarction and coronary artery bypass graft surgery. Unfortunately, there are few depression treatment studies in patients with CAD that make use of standardized HRQOL measures, but the limited evidence suggests that successful treatment has positive implications for HRQOL in these patients. The mechanisms through which depression impacts on HRQOL require further study but are likely to be behavioral. Depressive symptoms significantly undermine HRQOL in patients with CAD despite successful medical and surgical management. Although successful treatment of depression has not been shown to reduce mortality rates in patients with CAD, further study may find that the HRQOL benefits of such treatment are equally valuable.
Publisher: Springer Science and Business Media LLC
Date: 04-06-2019
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.MEHY.2007.04.001
Abstract: Vitamin D is known to be widely deficient in Western populations. The implications of this in terms of bone health are increasingly understood, yet its impact on other health areas, particularly mental health, is unclear. Recent data suggests that hypovitaminosis D may be common, especially in the elderly. Other studies have suggested that low levels of vitamin D are associated with poor mood. There are a number of trials that have suggested a role for Vitamin D in the supplementary treatment of depression. Dose may be a critical issue, as sun exposure and dietary intake may be low and high doses may be required.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.EURONEURO.2018.07.098
Abstract: There has been increasing interest in nutraceutical augmentation strategies to boost the efficacy of antidepressants. This study assessed whether S-adenosylmethionine (SAMe), a methyl donor that occurs naturally in the body, may be of such benefit. We conducted an 8-week, double-blind RCT in which 107 treatment non-remittent outpatients with DSM-5 diagnosed Major Depressive Disorder (MDD) were randomized to either SAMe or placebo adjunctively to antidepressants. One-carbon cycle nutrients, pertinent single nucleotide polymorphisms (SNPs), and BDNF were also analysed as potential moderators of response. A linear mixed-effects model revealed a significant overall reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score across time, however there was no significant between-group difference observed (p = 0.51). Response rates at Week 8 were 54.3% in the SAMe group and 50.0% in the placebo group, with remission rates 43.5% for SAMe and 38.3% for placebo (all results NS). No effect of SAMe was found on any secondary outcome. Differential response to SAMe was not modified by a range of key genotypes (e.g. COMT), nor reflected in a change of homocysteine, red cell folate, or BDNF. Use of SAMe elicited no significant adverse effects beyond placebo, however it was implicated in one case of serotonin syndrome-like symptoms. This study concludes that 800 mg/day of SAMe is not an effective adjunctive treatment in MDD, and no obvious biomarker reflected any differential response to treatment. Due to such a distinctly high placebo-response (despite rigorous screening), future studies should employ a placebo run-in period and other strategies to minimize placebo response.
Publisher: SAGE Publications
Date: 14-03-2013
Abstract: Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC). This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period. Fifteen participants were available for this report two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint. Although the s le size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed.
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000502652
Abstract: Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω–3 polyunsaturated fatty acids (n–3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n–3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n–3 PUFAs in depression treatment (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA & #x3e ) are considered effective, and the recommended dosages should be 1–2 g of net EPA daily, from either pure EPA or an EPA/DHA (& #x3e :1) formula (3) the quality of n–3 PUFAs may affect therapeutic activity and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n–3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.
Publisher: Wiley
Date: 29-07-2020
DOI: 10.1002/HBM.25098
Abstract: MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.NEUBIOREV.2010.10.001
Abstract: There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly erse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways.
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000334910
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.JAD.2014.02.018
Abstract: Major depression and bipolar disorder are accompanied by the activation of immune-inflammatory and Oxidative and Nitrosative Stress (O&NS) pathways and lowered levels of antioxidants. Paraoxonase (PON)1 (EC 3.1.8.1) is an antioxidant bound to High Density Lipoprotein (HDL). Polymorphisms in the PON1 Q192R coding sequence determine three functional genotypes, i.e. 192QQ, 192QR and 192RR. This study was carried out to delineate the associations of plasma PON1 activity and functional PON1 Q192R genotypes in major depression and bipolar disorder. PON1 status that is plasma PON1 abundance and three functional PON1 Q192R genotypes were assayed in 91 major depressed and 45 bipolar patients and compared to 199 normal controls. Major depression, but not bipolar disorder, was accompanied by lowered PON1 activity. PON1 activity was decreased by smoking and a diagnosis by genotype interaction (i.e. lower PON1 in major depression with the QQ genotype). Logistic regression showed that smoking by QQ genotype significantly increased the odds of bipolar disorder and that major depression was predicted by plasma PON1 activity, serum HDL cholesterol and interactions between genotype×smoking. The results suggest that lowered plasma PON1 activity is a trait marker of major depression and that PONQ192R gene-environment (smoking) interactions differentially predict the odds of depression and bipolar disorder. Association studies are prone to a risk of false positive findings and replication is essential. The findings suggest that there are differential PON1 Q192R functional genotype×environment interactions in major depression and bipolar disorder. The effects of lowered PON1 activity may contribute to increased O&NS and immune-inflammatory burden in depression. PON1 status may contribute to the comorbidity between depression and other immune- and O&NS-related disorders, e.g. cardiovascular disorder.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2019
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JAD.2015.04.025
Abstract: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated. We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests. The s le was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance. The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2020
DOI: 10.1186/S13063-019-3758-9
Abstract: People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes. The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline. The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis. ISRCTN, ISRCTN12424842 . Registered on 25 February 2015.
Publisher: SAGE Publications
Date: 13-01-2023
DOI: 10.1177/07067437221150508
Abstract: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial ( n = 15) of enema-delivered FMT ( n = 10) compared with a placebo enema ( n = 5) in adults with moderate-to-severe MDD. Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.
Publisher: Cambridge University Press (CUP)
Date: 30-06-2020
DOI: 10.1017/NEU.2020.25
Abstract: The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N -acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS). This study involved secondary analysis of a placebo-controlled randomised trial ( n = 163). Serum s les were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers. In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ 2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ 2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that in iduals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment ( p = 0.023). Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Publisher: Wiley
Date: 27-07-2021
DOI: 10.1111/EIP.13203
Abstract: There is a lack of existing research regarding young people with bipolar I disorder (BD‐I) and psychotic features, who are not in education, employment, and training (NEET). Thus, the aims of the study were to: (a) establish rates of NEET at service entry to a specialist early intervention service (b) delineate premorbid and current variables associated with NEET status at service entry and (c) examine correlates of NEET status at discharge. Medical file audit methodology was utilized to collect information on 118 patients with first episode psychotic mania treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. NEET status was determined using the modified vocation status index (MVCI). Bivariate and multivariable logistic variables were used to examine relationships between premorbid, service entry and treatment variables, and NEET status at service entry and discharge. The NEET rate was 33.9% at service entry, and 39.2% at discharge. Variables associated with NEET status at service entry were premorbid functioning and polysubstance use. NEET status at service entry was the only significant correlate of NEET status at discharge. When service entry NEET was taken out of the model, substance use during treatment was predictive of NEET status at discharge. NEET status at service entry was related to a history of premorbid decline, and risk factors such as substance use and forensic issues. NEET status can decline during treatment, and utility of vocational intervention programs specifically for BD, in addition to specialist early intervention, needs to be examined.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2012
Publisher: Wiley
Date: 20-08-2021
DOI: 10.1111/EIP.13204
Abstract: Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up‐skill patients and their families. The benefits of SEI over the first few years have been demonstrated. While early recovery can be expected to translate to better long‐term outcomes by analogy with other illnesses, there is limited evidence to support this from follow‐up studies. The current study involves the long‐term follow‐up of a sub‐set of first episode psychosis (FEP) patients, with a range of diagnoses, who were first treated at Orygen's Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. The aim of this paper is to present the methodology for this follow‐up study. Between January 1998 and December 2000, 786 patients between the ages of 15–29 years were treated at EPPIC, located in Melbourne, Australia. Our cohort consists of 661 people (82 were transferred/discharged and 43 were not diagnosed with a psychotic disorder at time of discharge). The 18‐month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The ≥15 year outcomes of this cohort are being examined in this study, known as FEPOS15. Participant follow‐up is ongoing. In order to extend and assess broader outcomes of the cohort, data linkage with health‐related databases will be conducted. This study will provide a comprehensive evaluation of the long‐term trajectory of psychotic disorders after treatment for FEP in a SEI service.
Publisher: BMJ
Date: 04-2019
DOI: 10.1136/BMJOPEN-2018-025640
Abstract: First line pharmacological treatments for bipolar disorder (BD) can leave shortfalls in recovery leading to patients seeking alternative and adjunctive treatments such as nutraceuticals. This protocol for a systematic review and proposed meta-analysis aims to answer the research question: in patients with BD, how does use of nutraceutical treatments compare with placebo in reducing depressive and mania symptoms? Clinical trials will be identified through database searches using PubMed via PubMed, EMBASE via embase.com, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com and CINAHL Complete via EBSCO. Search terms for BD and specific nutraceuticals (75 total search terms) will be used. Double-blind, randomised, controlled, clinical trials of adults with BD will be included in the review. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. This review will only look at published data (already reviewed for ethical compliance) therefore, ethical approval is not required. We aim to publish the systematic review in a peer-reviewed journal and present at conferences. CRD42019100745 .
Publisher: JMIR Publications Inc.
Date: 17-01-2022
Abstract: nternet delivered psychosocial interventions can overcome barriers with face-to-face psychosocial care. Limited evidence supports the cost-effectiveness of online psychosocial therapies for people with bipolar disorders. o conduct a within trial economic evaluation of an online intervention for people with bipolar disorder, Moodswings 2.0 from an Australian health sector perspective. oodswings comprised an economic evaluation alongside an international, parallel, in idually-stratified randomised controlled trial comparing an online discussion forum (control Group 1) to a discussion forum plus online psychoeducation (Group 2) and to a discussion forum plus psychoeducation and cognitive behavioural tools (Group 3). The trial enrolled adults (21 to 65 years) with a diagnosis of bipolar disorder assessed by phone using the Structured Clinical Interview for DSM-5. Health sector costs included intervention delivery and additional health care resources utilised by participants over the 12-month trial follow-up. Outcomes included depression symptoms measured by the Montgomery-Asberg Depression Rating Scale (MADRS) (the trial primary outcome), and quality adjusted life years (QALYs) calculated using SF-6D derived from the SF-12. Average incremental cost-effectiveness (cost/MADRS) and cost-utility (cost/QALY) ratios were calculated using estimated mean differences between intervention and control groups from linear mixed-effects models in the base case. Sensitivity analyses evaluated methods of managing missing data and varying key cost parameters. total of 304 participants were randomised. Average health sector cost was lowest for Group 2 ($9,705) compared to the control group ($15,175) and Group 3 ($15,518), but none were statistically significantly different. The average QALYs were not significantly different between groups (Group 1 0.627 Group 2 0.618 Group 3 0.622). MADRS scores were previously shown to differ significantly between Group 2 and the control group at all follow-up timepoints (p .05). Group 2 was dominant (lower costs and greater effects) compared to the control group for average incremental cost per point decrease in MADRS score over 12 months (95% CI: Dominated to $331). Average cost per point change in MADRS score for Group 3 versus control group was $156 (95% CI: Dominant to $22,585). Group 2 was dominant over the control group based on lower average health sector cost and average QALY benefit of 0.01 (95% CI: $43,000 to Dominant). There was an 86% probability that the psychoeducation modules would be cost-effective at the $50,000/QALY threshold. Group 3 compared to the control group had an average ICER of $173,315/QALY (95% CI: Dominated to $19,978) with a 47% probability of being cost-effective at the $50,000/QALY threshold. nline psychoeducation through the Moodswings 2.0 platform has the potential to be a cost-effective intervention for people with bipolar disorder. This component should be implemented with continuing evaluation. Additional research is required to understand the lack of response to the addition of online CBT tools. his study was registered with ClinicalTrials.gov NCT02106078 and NCT02118623. Ethical approval for the study was obtained by the Institutional Review Board at Stanford University (Stanford, CA, USA), the Barwon Health and Deakin University Human Research Ethics Committees (Geelong, Australia).
Publisher: SAGE Publications
Date: 08-04-2019
Publisher: Oxford University Press (OUP)
Date: 10-2015
DOI: 10.5665/SLEEP.5056
Publisher: SAGE Publications
Date: 03-2012
Publisher: SAGE Publications
Date: 31-10-2018
Abstract: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge ‘impairment’ (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.
Publisher: SAGE Publications
Date: 28-08-2013
Publisher: Wiley
Date: 13-05-2020
DOI: 10.1111/JGS.16468
Publisher: Elsevier BV
Date: 2021
Publisher: SAGE Publications
Date: 07-09-2015
Publisher: Oxford University Press (OUP)
Date: 04-01-2014
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.NEUBIOREV.2017.01.014
Abstract: Bipolar disorder phenomenologically is a biphasic disorder of energy availability increased in mania and decreased in depression. In consort, there is accumulating evidence indicating increased mitochondrial respiration and ATP production in bipolar mania which contrasts with decreased mitochondrial function in patients in the euthymic or depressive phase of the illness. Consequently, the central thesis of this paper is that bipolar disorder is due to a phasic dysregulation of mitochondrial biogenergetics. The elements responsible for this dysregulation may thus represent critical treatment targets for mood disorders, and are the subject of this paper. There are many potential mediators of mitochondrial function which collectively are implicated in bipolar disorder. Levels of oxidative stress, pro-inflammatory cytokines and intracellular calcium ions are all higher in bipolar mania than in the euthymic and depressive phases of the illness. Increased levels of calcium ions can partly account for increased oxidative phosphorylation via well documented pathways such as the modulation of the F Details of these pathways are discussed as an explanatory model for the existence of increased ATP generation in mania. We also offer a model explaining the biphasic nature of mitochondrial respiration in bipolar disorder and the transition between mania and depression based on increasing levels of TNFα, ROS, NO, AMPK and SIRT-1 together with the antagonistic relationship between p53 and NF-κB.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2019
Publisher: Wiley
Date: 10-01-2008
DOI: 10.1111/J.1399-5618.2007.00556.X
Abstract: The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2012
DOI: 10.1007/S00127-011-0421-5
Abstract: Self-rated health has been linked to important health and survival outcomes in in iduals with co-morbid depression and cardiovascular disease (CVD). It is not clear how the timing of depression onset relative to CVD onset affects this relationship. We aimed to first identify the prevalence of major depressive disorder (MDD) preceding CVD and secondly determine whether sequence of disease onset is associated with mental and physical self-rated health. This study utilised cross-sectional, population-based data from 224 respondents of the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). Participants were those diagnosed with MDD and reported ever having a heart/circulatory condition over their lifetime. Age of onset was reported for each condition. Logistic regression was used to explore differences in self-rated mental and physical health for those reporting pre-cardiac and post-cardiac depression. The proportion of in iduals in whom MDD preceded CVD was 80.36% (CI: 72.57-88.15). One-fifth (19.64%, CI: 11.85-27.42) reported MDD onset at the time of, or following, CVD. After controlling for covariates, the final model demonstrated that those reporting post-cardiac depression were significantly less likely to report poor self-rated mental health (OR:0.36, CI: 0.14-0.93) than those with pre-existing depression. No significant differences were found in self-rated physical health between groups (OR:0.90 CI: 0.38-2.14). MDD is most common prior to the onset of CVD. Further, there is an association between pre-morbid MDD and poorer self-rated mental health. To our knowledge, this is the first time this has been demonstrated in a national, population-based survey. As self-rated health has been shown to predict important outcomes such as survival, we recommend that those with MDD be identified as vulnerable to CVD onset and poorer health outcomes.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.NEURON.2019.01.004
Abstract: Neuroethics is central to the Australian Brain Initiative's aim to sustain a thriving and responsible neurotechnology industry. Diverse and inclusive community and stakeholder engagement and a trans-disciplinary approach to neuroethics will be key to the success of the Australian Brain Initiative.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Springer Science and Business Media LLC
Date: 24-01-2217
DOI: 10.1038/TP.2016.281
Abstract: Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients ( n =26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control s le was also collected ( n =20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l −1 , n =20) or quetiapine (flexibly dosed up to 800 mg per day, n =19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally ( t 1,66 .20, P .01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F 2,112 =8.54, P .01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months ( t 1,24 =3.76, P .01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.
Publisher: Wiley
Date: 14-11-2020
DOI: 10.1002/JGH3.12278
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JPSYCHIRES.2022.03.025
Abstract: The molecular mechanism(s) underpinning the clinical efficacy of the current drugs for bipolar disorder (BD) are largely unknown. This study evaluated the transcriptional perturbations potentially playing roles in the therapeutic efficacy of four commonly prescribed psychotropic drugs used to treat BD. NT2-N cells were treated with lamotrigine, lithium, quetiapine, valproate or vehicle control for 24 h. Genome-wide mRNA expression was quantified by RNA-sequencing. Incorporating drug-induced gene expression profiles with BD-associated transcriptional changes from post-mortem brains, we identified potential therapeutic-relevant genes associated with both drug treatments and BD pathophysiology and focused on expression quantitative trait loci (eQTL) genes with genome-wide association with BD. Each eQTL gene was ranked based on its potential role in the therapeutic effect across multiple drugs. The expression of highest-ranked eQTL genes were measured by RT-qPCR to confirm their transcriptional changes observed in RNA-seq. We found 775 genes for which at least 2 drugs reversed expression levels relative to the differential expression in post-mortem brains. Pathway analysis identified enriched biological processes highlighting mitochondrial and endoplasmic reticulum function. Differential expression of SRPK2 and CHDH was confirmed by RT-qPCR following multiple-dose treatments. We pinpointed potential genes involved in the beneficial effects of drugs used for BD and their main associated biological pathways. CHDH, which encodes a mitochondrial protein, had a significant dose-responsive downregulation following treatment with increasing doses of quetiapine and lamotrigine, which in combination with the enriched mitochondrial pathways suggests potential therapeutic roles and demand more studies on mitochondrial involvement in BD to identify novel treatment targets.
Publisher: Springer Science and Business Media LLC
Date: 24-10-2013
Publisher: Cambridge University Press (CUP)
Date: 08-2009
DOI: 10.1111/J.1601-5215.2009.00399.X
Abstract: Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian s le. Participants ( n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode. Three AAO groups were compared: early (AAO 20, mean = 15.5 ± 2.72 44.4% of the participants) intermediate (AAO 20–39, mean = 26.1 ± 4.8 48.14% of the participants) and late (AAO 40, mean = 50.6 ± 9.04 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance. Early AAO is associated with an adverse outcome.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.LFS.2014.02.033
Abstract: This study examined whether Castelli risk indexes 1 (total/high-density lipoprotein (HDL) cholesterol) and 2 (low density lipoprotein (LDL)/HDL cholesterol) and other shared metabolic disorders might underpin the pathophysiology of the metabolic syndrome, major depression or bipolar disorder. This cross-sectional study examined 92 major depressed, 49 bipolar depressed and 201 normal controls in whom the Castelli risk indexes 1 and 2 and key characteristics of the metabolic syndrome, i.e. waist/hip circumference, body mass index (BMI), systolic/diastolic blood pressure, total cholesterol, low-density lipoprotein (LDL) and HDL cholesterol, triglycerides, insulin, glucose, hemoglobin A1c (HbA1c) and homocysteine were assessed. Castelli risk indexes 1 and 2 were significantly higher in major depressed patients than in bipolar disorder patients and controls. There were no significant differences in waist or hip circumference, total and LDL cholesterol, triglycerides, plasma glucose, insulin, homocysteine and HbA1c between depression and bipolar patients and controls. Bipolar patients had a significantly higher BMI than major depressed patients and normal controls. Major depression is accompanied by increased Castelli risk indexes 1 and 2, which may be risk factors for cardiovascular disease. Other key characteristics of the metabolic syndrome, either metabolic biomarkers or central obesity, are not necessarily specific to major depression or bipolar disorder.
Publisher: SAGE Publications
Date: 20-06-2017
Publisher: Wiley
Date: 18-10-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2011
Publisher: Springer Science and Business Media LLC
Date: 27-03-2022
DOI: 10.1186/S12888-022-03840-3
Abstract: There is increasing recognition of the substantial burden of mental health disorders at an in idual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a ‘first-line’, ‘non-negotiable’ treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an in idually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks. The study is being conducted in partnership with Barwon Health’s Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance. If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support in iduals experiencing psychological distress. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12621000387820 , Registered 8 April 2021.
Publisher: JMIR Publications Inc.
Date: 15-04-2019
DOI: 10.2196/13493
Abstract: Self-management is increasingly recognized as an important method through which in iduals with bipolar disorder (BD) may cope with symptoms and improve quality of life. Digital health technologies have strong potential as a method to support the application of evidence-informed self-management strategies in BD. Little is known, however, about how to most effectively maximize user engagement with digital platforms. The aims of this study were (1) to create an innovative Web-based Bipolar Wellness Centre, (2) to conduct a mixed-methods (ie, quantitative and qualitative) evaluation to assess the impact of different sorts of engagement (ie, knowledge translation [KT]), and (3) to support engagement with the self-management information in the Bipolar Wellness Centre. The project was implemented in 2 phases. In phase 1, community-based participatory research and user-centered design methods were used to develop a website (Bipolar Wellness Centre) housing evidence-informed tools and strategies for self-management of BD. In phase 2, a mixed-methods evaluation was conducted to explore the potential impact of 4 KT strategies (Web-based webinars, Web-based videos, Web-based one-to-one Living Library peer support, and in-person workshops). Quantitative assessments occurred at 2 time points—preintervention and 3 weeks postintervention. Purposive s ling was used to recruit a subs le of participants for the qualitative interviews, ensuring each KT modality was represented, and interviews occurred approximately 3 weeks postintervention. A total of 94 participants were included in the quantitative analysis. Responses to evaluative questions about engagement were broadly positive. When averaged across the 4 KT strategies, significant improvements were observed on the Bipolar Recovery Questionnaire (F1,77=5.887 P=.02) and Quality of Life in Bipolar Disorder (F1,77=8.212 P=.005). Nonsignificant improvements in positive affect and negative affect were also observed. The sole difference that emerged between KT strategies related to the Chronic Disease Self-Efficacy measure, which decreased after participation in the webinar and video arms but increased after the Living Library and workshop arms. A subs le of 43 participants was included in the qualitative analyses, with the majority of participants describing positive experiences with the 4 KT strategies peer contact was emphasized as a benefit across all strategies. Infrequent negative experiences were reported in relation to the webinar and video strategies, and included technical difficulties, the academic tone of webinars, and feeling unable to relate to the actor in the videos. This study adds incremental evidence to a growing literature that suggests digital health technologies can provide effective support for self-management for people with BD. The finding that KT strategies could differentially impact chronic disease self-efficacy (hypothesized as being a product of differences in degree of peer contact) warrants further exploration. Implications of the findings for the development of evidence-informed apps for BD are discussed in this paper.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.PNPBP.2014.10.002
Abstract: Schizophrenia is a chronic and often debilitating disorder in which stage of illness appears to influence course, outcome, prognosis and treatment response. Current evidence suggests roles for oxidative, neuroinflammatory, neurotrophic, apoptotic, mitochondrial and glutamatergic systems in the disorder all targets of N-acetyl cysteine (NAC). A double blind, placebo controlled trial suggested NAC to be beneficial to those diagnosed with schizophrenia. The current manuscript aims to investigate duration of the illness as a key factor that may be modulating the response to NAC in the participants who took part in the study. A s le of 121 participants were randomised in a double fashion to 24 weeks (placebo=62 NAC=59). Clinical and functional variables were collected over the treatment period. Duration of the illness at baseline was grouped into <10 years, 10- 20 years. Mixed Model Repeated Measures Analysis was used to explore the effect of illness duration on response to treatment with NAC. A significant interaction between duration of the illness and response to treatment with NAC was consistently found for positive symptoms and functional variables, but not for negative or general symptoms or for side effect related outcomes. The pattern of changes suggests that this mediator effect of duration of illness in response to treatment is more evident in those participants with 20 years or more of illness duration. Our results suggest a potential advantage of adjunctive NAC over placebo on functioning and positive symptoms reduction in those patients with chronic schizophrenia. This has potential for suggesting stage specific treatments.
Publisher: Wiley
Date: 08-2010
DOI: 10.1111/J.1399-5618.2010.00834.X
Abstract: There is a growing body of evidence implicating oxidative stress and the glutathione system in the pathogenesis of major psychiatric illnesses, including schizophrenia and bipolar disorder. Here we investigate whether genes involved in oxidative stress regulation are associated with increased risk for bipolar disorder. Four candidate genes were selected a priori from two different steps in the oxidative stress pathway, specifically the synthesis of glutathione [catalytic subunit of glutamate cysteine ligase (GCLC) and regulatory subunit of glutamate cysteine ligase (GCLM)] and the removal of reactive oxygen species [superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3)]. Haplotype tagging and functional nucleotide polymorphisms were selected in each gene and tested for association with bipolar disorder under narrow (n = 240) and broad (n = 325) phenotypic models, compared to healthy controls (n = 392, comprising 166 psychiatrically assessed unaffected controls plus 226 healthy in iduals). Single marker association analysis did not reveal significant association with bipolar disorder however, haplotypes in the SOD2 gene showed nominal association (global chi(2) = 8.94, p = 0.03 broad model). Interaction analysis revealed a significant interaction between SOD2 and GPX3 haplotypes, which further increases risk for bipolar disorder (odds ratio = 2.247, chi(2) = 9.526, p = 0.002, corrected p = 0.029). Further characterization of the SOD2 and GPX3 interaction using larger cohorts is required to determine the role of these oxidative pathway genes as risk factors for bipolar disorder.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
DOI: 10.1038/TP.2017.190
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.SCHRES.2014.06.032
Abstract: Cognitive symptoms and impairment are central to schizophrenia and often an early sign of this condition. The present study investigated biological correlates of cognitive symptoms and performance in in iduals at ultra-high risk (UHR) for psychosis. The study s le comprised 80 neuroleptic-naïve UHR in iduals aged 13-25 years. Associations among erythrocyte membrane fatty acid levels, measured by gas chromatography, and cognitive functioning were investigated in UHR patients. Subjects were ided into terciles based on their scores on the cognitive factor of the Positive and Negative Syndrome Scale. The Zahlen-Verbindungs Test (ZVT) (the number-combination test) was also used as a measure of information-processing speed. Exploratory analysis was conducted to investigate the relationship between membrane fatty acid levels with the size of the intracranial area (ICA), a neurodevelopmental measure relevant to schizophrenia, in half of subjects (n=40) using magnetic resonance imaging. The adjusted analysis revealed that omega-9 eicosenoic and erucic acid levels were significantly higher, but omega-3 docosahexaenoic acid levels were significantly lower, in the cognitively impaired than in the cognitively intact group. We found a significant negative association of eicosenoic, erucic, and gamma-linoleic acids with ZVT scores. A negative association between ICA and membrane levels of eicosenoic acid was also found. This is the first study to demonstrate the relationship between membrane fatty acids and cognitive function in neuroleptic-naïve subjects at UHR for psychosis. The study findings indicate that abnormalities in membrane fatty acids may be associated with the neurodevelopmental disruption associated with the cognitive impairments of in iduals at UHR for psychosis.
Publisher: Wiley
Date: 30-03-2017
DOI: 10.1111/EIP.12340
Abstract: Early intervention and prevention of serious mental disorders such as bipolar disorder has the promise of decreasing the burden associated with these disorders. With increasing early and preventive intervention efforts among cohorts such as those with a familial risk for bipolar disorder, there is a need to examine the associated ethical concerns. The aim of this review was to examine the ethical issues underpinning the clinical research on pre-onset identification and preventive interventions for bipolar disorder. We undertook a PubMed search updated to November 2014 incorporating search terms such as bipolar, mania, hypomania, ethic*(truncated), early intervention, prevention, genetic and family. Fifty-six articles that were identified by this method as well as other relevant articles were examined within a framework of ethical principles including beneficence, non-maleficence, respect for autonomy and justice. The primary risks associated with research and clinical interventions include stigma and labelling, especially among familial high-risk youth. Side effects from interventions are another concern. The benefits of preventive or early interventions were in the amelioration of symptoms as well as the possibility of minimizing disability, cognitive impairment and progression of the illness. Supporting the autonomy of in iduals and improving access to stigma-free care may help moderate the potential challenges associated with the risks of interventions. Concerns about the risks of early identification and pre-onset interventions should be balanced against the potential benefits, the in iduals' right to choice and by improving availability of services that balance such dilemmas.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Publisher: Elsevier BV
Date: 07-2021
Publisher: MDPI AG
Date: 02-07-2021
DOI: 10.3390/IJMS22137164
Abstract: Recent reports suggest a link between positive regulation of the Hippo pathway with bipolar disorder (BD), and the Hippo pathway is known to interact with multiple other signaling pathways previously associated with BD and other psychiatric disorders. In this study, neuronal-like NT2 cells were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM), or vehicle control for 24 h. Genome-wide mRNA expression was quantified and analyzed using gene set enrichment analysis (GSEA), with genes belonging to Hippo, Wnt, Notch, TGF- β, and Hedgehog retrieved from the KEGG database. Five of the eight drugs downregulated the genes of the Hippo pathway and modulated several genes involved in the interacting pathways. We speculate that the regulation of these genes, especially by aripiprazole, clozapine, and quetiapine, results in a reduction of MAPK and NFκB pro-inflammatory signaling through modulation of Hippo, Wnt, and TGF-β pathways. We also employed connectivity map analysis to identify compounds that act on these pathways in a similar manner to the known psychiatric drugs. Thirty-six compounds were identified. The presence of antidepressants and antipsychotics validates our approach and reveals possible new targets for drug repurposing.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2014
DOI: 10.1038/MP.2014.33
Abstract: Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean = 35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.
Publisher: Springer Science and Business Media LLC
Date: 04-11-2014
Publisher: Elsevier BV
Date: 03-2023
DOI: 10.1016/J.PNPBP.2022.110687
Abstract: Despite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage. We completed a secondary analysis of baseline data from a randomised control trial of BD in iduals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction. The FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis. Cortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of in iduals with more established BD may be more attributable to post-onset factors.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2012
DOI: 10.1007/S00127-012-0623-5
Abstract: In this study, we aimed to examine the relationship between diet quality and depression in a prospective study of adolescents from varied ethnic and cultural backgrounds. In this prospective cohort study, data were collected at two time points (2001 and 2003) from nearly 3,000 adolescents, aged either 11-12 years or 13-14 years, participating in RELACHS, a study of ethnically erse and socially deprived young people from East London in the UK. Diet quality was measured from dietary questionnaires, and mental health assessed using the Strengths and Difficulties Questionnaire (SDQ) and the Short Mood and Feelings Questionnaire (SMFQ). In cross-sectional analyses, we found evidence for an association between an unhealthy diet and mental health problems. Compared to those in the lowest quintile of Unhealthy diet score, those in the highest quintile were more than twice as likely to be symptomatic on the SDQ (OR 2.10, 95 %CI 1.38-3.20) after taking all identified confounders into account. There was also some evidence for a cross-sectional inverse association between a measure of healthy diet and mental health problems. A prospective relationship between the highest quintiles of both Healthy (OR 0.63, 95 %CI 0.38-1.05) and Unhealthy (OR 1.75, 95 %CI 1.00-3.06) diet scores and SDQ scores at follow-up was also evident, but was attenuated by final adjustments for confounders. This study is concordant with previous observational studies in describing relationships between measures of diet quality and mental health problems in adolescents.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.PSYCHRES.2012.11.026
Abstract: While psychotherapies are of established value, they may, as active treatments, risk adverse outcomes. As there is no validated measure of potentially negative psychotherapeutic ingredients, we sought to develop such a measure for use in psychotherapy evaluation studies. Based on a review of the literature, a 103-item experiential measure was derived. Psychometric properties and scale score correlates were examined in a s le of more than 700 respondents. Principal component analyses revealed a five-factor solution, explaining 53.4% of the variance namely 'Negative Therapist', 'Pre-occupying Therapy', 'Beneficial Therapy', 'Idealization of Therapist' and 'Passive Therapist' constructs. Derived factors had high internal consistency, and scale scores were correlated with a number of clinically relevant demographic and treatment characteristics. An independent study established high test-retest reliability for the measure. Assessment of any adverse effects of psychotherapy is of clinical and research significance. We report the development of a measure that should allow the impact of such effects to be quantified in treatment studies, and especially in apportioning the contribution of such non-specific therapeutic effects.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAD.2019.03.003
Abstract: Maladaptive perfectionism is a transdiagnostic risk and maintaining factor for a range of mental health conditions, including bipolar disorder (BD). Self-compassion represents a potential protective factor against maladaptive perfectionism, however no studies to date have examined the relationship of these constructs in BD. The aim of the present study was to examine associations between maladaptive perfectionism, self-compassion and symptoms among in iduals with BD. Baseline data were collected from 302 participants with a DSM-IV diagnosis of BD participating in an international randomised controlled trial. Participants completed measures of maladaptive perfectionism, self-compassion, symptom severity and emotion regulation difficulties. Clinician-administered measures of depression and mania severity were additionally collected. Correlation and mediation analyses were conducted. Maladaptive perfectionism was positively associated with depression, anxiety and emotion regulation difficulties. Lower levels of self-compassion correlated with greater self-reported depression, anxiety and emotion regulation difficulties. Self-compassion partially mediated relationships between maladaptive perfectionism, depression, anxiety and emotion regulation difficulties. The cross-sectional design limits conclusions about causal relationships between study variables. Results may not be generalizable to other BD populations. The role of maladaptive perfectionism and self-compassion in elevated mood states of BD remains unclear. Self-compassion represents one mechanism through which maladaptive perfectionism influences symptoms of depression, anxiety and emotion regulation difficulties in BD. Self-compassion represents a modifiable treatment target in iduals with BD exhibiting maladaptive perfectionistic tendencies may benefit from interventions fostering self-compassion.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2012
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.BIOPSYCH.2008.04.022
Abstract: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorder are complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder. A randomized, double-blind, multicenter, placebo-controlled study of in iduals (n = 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning. NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: -8.05 [-13.16, -2.95], p = .002) and most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p = .968) and no significant between-group differences in adverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts. NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2013
Publisher: EDITORA SCIENTIFIC
Date: 12-2011
DOI: 10.1590/S1516-44462011000400011
Abstract: OBJECTIVE: In this report, we aimed to evaluate the effect of add-on N-acetylcysteine (NAC) on depressive symptoms and functional outcomes in bipolar disorder. To that end, we conducted a secondary analysis of all patients meeting full criteria for a depressive episode in a placebo controlled trial of adjunctive NAC for bipolar disorder. METHOD: Twenty-four week randomised clinical trial comparing adjunctive NAC and placebo in in iduals with bipolar disorder experiencing major depressive episodes. Symptomatic and functional outcome data were collected over the study period. RESULTS: Seventeen participants were available for this report. Very large effect sizes in favor of NAC were found for depressive symptoms and functional outcomes at endpoint. Eight of the ten participants on NAC had a treatment response at endpoint the same was true for only one of the seven participants allocated to placebo. DISCUSSION: These results indicate that adjunctive NAC may be useful for major depressive episodes in bipolar disorder. Further studies designed to confirm this hypothesis are necessary.
Publisher: Wiley
Date: 14-10-2005
DOI: 10.1111/J.1399-5618.2005.00254.X
Abstract: To examine the nature of executive deficits in euthymic patients with bipolar disorder (BD). Fifteen euthymic BD patients and 13 controls were administered a battery of executive tasks including verbal fluency, Stroop, Theory of Mind (ToM) tests and selected subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Self-report and clinician ratings of mood and social and occupational functioning were also obtained. There were no significant differences between BD patients and controls on the primary measures of the following executive tasks: verbal fluency, attentional set-shifting, problem solving or planning. On secondary measures of speed, BD patients were slower to complete the first trial of the Stroop task (p = 0.001). Patients with BD committed more errors across all secondary measures. Patients performed poorly when compared with controls on tests of verbal ToM (p = 0.02), and although they performed non-verbal ToM tasks at a level comparable to controls (p = 0.60), they were slower to initiate a response (p = 0.006). ToM was not significantly correlated with any measure of social and occupational functioning however it correlated with the achievement scores of the CANTAB Stockings of Cambridge task (Pearson's r = 0.68, p < 0.01). Deficits found in euthymic bipolar patients suggest fronto-subcortical pathway dysfunction. This is consistent with other neuropsychological and neuroimaging research that points to a trait deficit in BD. Further investigation is necessary perhaps using more real-world tests.
Publisher: Informa UK Limited
Date: 03-04-2021
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.PLEFA.2015.07.001
Abstract: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). In 64 help-seeking UHR-in iduals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.
Publisher: SAGE Publications
Date: 06-11-2015
Abstract: Given the burden of common psychiatric disorders and their consequent service and planning requirements, it is important to have a thorough knowledge of their distribution and characteristics in the population. Thus, we aimed to report the prevalence and age of onset of mood, anxiety and substance-use disorders in an age-stratified representative s le of Australian men. Psychiatric disorders (mood, anxiety and substance-use disorders) were diagnosed utilising a structured clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition, Non-Patient Edition) for 961 men aged 24–98 years enrolled in the Geelong Osteoporosis Study. The lifetime and current prevalence of these disorders was determined from the study population and standardised to 2006 census data for Australia. Approximately one in three men (28.8%, 95% confidence interval [CI] = [26.8%, 30.8%]) reported a lifetime history of any psychiatric disorder, with mood disorders (18.2%, 95% CI = [15.2%, 21.2%]) being more prevalent than anxiety (7.2%, 95% CI = [5.0%, 9.4%]) and substance-use disorders (12.9%, 95% CI = [9.7%, 16.0%]). Approximately 8.7% (95% CI = [7.5%, 10.0%]) were identified as having a current disorder, with 3.8% (95% interquartile range [IQR] = [2.2%, 5.4%]), 2.4% (95% CI = [1.1%, 3.8%]) and 3.4% (95% CI = [1.8%, 4.9%]) meeting criteria for current mood, anxiety and substance-use disorders, respectively. The median age of onset for mood disorders was 37.5 years (IQR = 27.0–48.0 years), 25.0 years (IQR = 20.0–40.3 years) for anxiety and 22.0 years (IQR = 18.0–34.3 years) for substance-use disorders. This study reports the lifetime and current prevalence of psychiatric disorders in the Australian male population. These findings emphasise the extent of the burden of these disorders in the community.
Publisher: MDPI AG
Date: 06-10-2020
DOI: 10.3390/NU12103055
Abstract: The association between dairy product consumption and biomarkers of inflammation, adipocytokines, and oxidative stress is poorly studied in children. Therefore, these associations were examined in a representative subs le of 1338 schoolchildren with a mean age of 11.5 (±0.7) years in the Healthy Growth Study. Information on dairy product consumption was collected by dietary recalls. Total dairy consumption was calculated by summing the intake of milk, yogurt, and cheese. Inflammatory markers, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and adipocytokines, i.e., leptin, adiponectin, and the antioxidant enzyme glutathione peroxidase (GPx) were analysed. Due to the skewed distribution hs-CRP, IL-6, and leptin were log transformed. Multivariable regression analyses adjusted for age, sex, energy intake, physical activity, parental education, Tanner stage, and fat mass were used to assess the associations between consumption of total dairy, milk, yogurt, cheese, and markers of inflammation, adipocytokines, oxidative stress, and adiponectin−leptin ratio. Our results showed that milk consumption was inversely associated with leptin (β: −0.101 95% CI: −0.177, −0.025, p = 0.009) and positively associated with the adiponectin−leptin ratio (β: 0.116 95% CI: 0.020, 0.211 p = 0.018), while total dairy, cheese, and yogurt consumption were not associated with inflammatory, adipocytokine, or antioxidant markers. Further prospective studies are needed to confirm these results.
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000381831
Publisher: SAGE Publications
Date: 29-10-2020
Abstract: We aimed to explore the relationships between diet quality, dietary inflammatory potential or body mass index and outcomes of a clinical trial of nutraceutical treatment for bipolar depression. This is a sub-study of a randomised controlled trial of participants with bipolar depression who provided dietary intake data ( n = 133). Participants received 16 weeks adjunctive treatment of either placebo or N-acetylcysteine-alone or a combination of mitochondrial-enhancing nutraceuticals including N-acetylcysteine (combination treatment). Participants were followed up 4 weeks post-treatment discontinuation (Week 20). Diet was assessed by the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies, Version 2, converted into an Australian Recommended Food Score to measure diet quality, and energy-adjusted dietary inflammatory index score to measure inflammatory potential of diet. Body mass index was also measured. Generalised estimating equation models were used to assess whether diet quality, energy-adjusted dietary inflammatory index score and/or body mass index were predictors of response to significant outcomes of the primary trial: depression symptoms, clinician-rated improvement and functioning measures. In participants taking combination treatment compared to placebo, change in depression scores was not predicted by Australian Recommended Food Score, dietary inflammatory index or body mass index scores. However, participants with better diet quality (Australian Recommended Food Score) reported reduced general depression and bipolar depression symptoms ( p = 0.01 and p = 0.03, respectively) and greater clinician-rated improvement ( p = 0.02) irrespective of treatment and time. Participants who had a more anti-inflammatory dietary inflammatory index had less impairment in functioning ( p = 0.01). Combination treatment may attenuate the adverse effects of pro-inflammatory diet ( p = 0.03) on functioning. Participants with lower body mass index who received combination treatment ( p = 0.02) or N-acetylcysteine ( p = 0.02) showed greater clinician-rated improvement. These data support a possible association between diet (quality and inflammatory potential), body mass index and response to treatment for bipolar depression in the context of a nutraceutical trial. The results should be interpreted cautiously because of limitations, including numerous null findings, modest s le size and being secondary analyses.
Publisher: Korean College of Neuropsychopharmacology
Date: 31-05-2019
Publisher: Cambridge University Press (CUP)
Date: 12-2009
DOI: 10.1111/J.1601-5215.2009.00397.X
Abstract: To evaluate the effect of N-acetylcysteine (NAC) on substance use in a double-blind, placebo-controlled trial of NAC in bipolar disorder. It is hypothesised that NAC will be superior to placebo for reducing scores on the Clinical Global Impressions scale for Substance Use (CGI-SU). Participants were randomised to a 6-months of treatment with 2 g/day NAC (n = 38) or placebo (n = 37). Substance use was assessed at baseline using a Habits instrument. Change in substance use was assessed at regular study visits using the CGI-SU. Among the 75 participants 78.7% drank alcohol (any frequency), 45.3% smoked tobacco and 92% consumed caffeine. Other substances were used by fewer than six participants. Caffeine use was significantly lower for NAC-treated participants compared to placebo at week 2 of treatment but not at other study visits. NAC appeared to have little effect on the participants who were using substances. A larger study on a substance-using population will be necessary to determine if NAC may be a useful treatment for substance use.
Publisher: SAGE Publications
Date: 27-07-2018
Abstract: It is well established that depression and non-communicable diseases are highly co-morbid and bi-directional in nature. ‘Lifestyle medicine’ has recently gained traction in the field of psychiatry, aimed at improvement of both physical and mental health. Online interventions can be an effective and inexpensive alternative or supplement to therapy that is delivered using more traditional modes, overcoming barriers that may prohibit people from accessing treatment by promoting flexibility and accessibility. This systematic review evaluates the existing evidence for the efficacy or effectiveness of lifestyle interventions for (1) in iduals with depressive symptoms, (2) clinically depressed populations or discussing the outcomes of depression within a subset of a larger cohort that are delivered online or via smart phone. Included studies were randomised controlled trials, with active comparator conditions, in adult populations and with reported lifestyle and depression-related outcomes. The analysis examined attrition, engagement, adherence and behaviour change techniques employed to achieve the target behaviours. Seven studies were included in the review and targeted behaviour change in five domains: alcohol reduction, improved sleep quality/insomnia reduction, increased physical activity, reduced/cessation of substance abuse and smoking cessation. Four of the studies achieved significant improvements in the targeted behaviour of these three also reported significant improvements in depressive symptoms. No studies reported significant improvements in depressive symptoms without a change in the target lifestyle behaviour. The results of this review highlight the potential of online lifestyle interventions as adjunctive treatments for depression, and the possibility of achieving significant improvements in depressive symptoms when targeting lifestyle behaviour change.
Publisher: SAGE Publications
Date: 09-2011
DOI: 10.3109/00048674.2011.595686
Abstract: Objective: This paper aims to present an overview of screening and safety considerations for the treatment of clinical depressive disorders and make recommendations for safety monitoring. Method: Data were sourced by a literature search using MEDLINE and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content. Results: Screening and monitoring can detect medical causes of depression. Specific adverse effects associated with antidepressant treatments may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment. Conclusion: The adoption of safety monitoring guidelines when treating clinical depression is likely to improve overall physical health status and treatment outcome. It is important to implement these guidelines in the routine management of clinical depression.
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JAAC.2013.07.002
Abstract: Diet quality is related to the risk for depression and anxiety in adults and adolescents however, the possible impact of maternal and early postnatal nutritional exposures on children's subsequent mental health is unexplored. The large prospective Norwegian Mother and Child Cohort Study recruited pregnant women between 1999 and 2008. Data were collected from mothers during pregnancy and when children were 6 months and 1.5, 3, and 5 years of age. Latent growth curve models were used to model linear development in children's internalizing and externalizing problems from 1.5 to 5 years of age as a function of diet quality during pregnancy and at 1.5 and 3 years. Diet quality was evaluated by dietary pattern extraction and characterized as "healthy" or "unhealthy." The s le comprised 23,020 eligible women and their children. Adjustments were made for variables including sex of the child, maternal depression, maternal and paternal age, maternal educational attainment, household income, maternal smoking before and during pregnancy, mothers' parental locus of control, and marital status. Higher intakes of unhealthy foods during pregnancy predicted externalizing problems among children, independently of other potential confounding factors and childhood diet. Children with a high level of unhealthy diet postnatally had higher levels of both internalizing and externalizing problems. Moreover, children with a low level of postnatal healthy diet also had higher levels of both internalizing and externalizing problems. Among this large cohort of mothers and children, early nutritional exposures were independently related to the risk for behavioral and emotional problems in children.
Publisher: Wiley
Date: 03-08-2012
Publisher: Elsevier BV
Date: 2021
Publisher: American Medical Association (AMA)
Date: 10-2017
Publisher: Informa UK Limited
Date: 09-11-2020
Publisher: Elsevier BV
Date: 09-2022
Publisher: Cambridge University Press (CUP)
Date: 25-09-2017
DOI: 10.1017/S0029665117002026
Abstract: Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n -3 fatty acids, folate, S -adenosylmethionine, N -acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: SAGE Publications
Date: 12-06-2013
Publisher: Wiley
Date: 26-03-2013
DOI: 10.1002/BRB3.137
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.JAD.2011.04.051
Abstract: In Obsessive Compulsive Disorder (OCD) current standard pharmacotherapies may be of limited efficacy. Non-conventional interventions such as Complementary and Alternative Medicine (CAM), self-help techniques, and lifestyle interventions are commonly used by sufferers of OCD, however to date no systematic review of this specific area exists. We conducted a systematic review of studies using CAM, self-help, and lifestyle interventions for treatment of OCD and trichotillomania (TTM). PubMed, PsycINFO, China Academic Journals Full-text Database, The Cochrane Library and CINAHL were searched (up to Jan 11th 2011), for controlled clinical trials using non-conventional interventions for OCD. A quality analysis using a purpose-designed scale and an estimation of effect sizes (Cohen's d) where data was available, were also calculated. The literature search revealed 14 studies that met inclusion criteria. Methodological quality of nutraceutical studies (nutrients and herbal medicines) were rated as high (mean 8.6/10), whereas mind-body or self-help studies were poorer (mean 6.1/10). In OCD, tentative evidentiary support from methodologically weak studies was found for mindfulness meditation (d=0.63), electroacupuncture (d=1.16), and kundalini yoga (d=1.61). Better designed studies using the nutrient glycine (d=1.10), and traditional herbal medicines milk thistle (insufficient data for calculating d) and borage (d=1.67) also revealed positive results. A rigorous study showed that N-acetylcysteine (d=1.31) was effective in TTM, while self-help technique "movement decoupling" also demonstrated efficacy (d=0.94). Mixed evidence was found for myo-inositol (mean d=0.98). Controlled studies suggest that St John's wort, EPA, and meridian-tapping are ineffective in treating OCD. While several studies were positive, these were un-replicated and commonly used small s les. This precludes firm confidence in the strength of clinical effect. Preliminary evidence however is encouraging, and more rigorous research of some of the more hypothesis-based interventions in the treatment of OCD and TTM may be indicated.
Publisher: Royal College of Psychiatrists
Date: 11-2021
Abstract: Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality. This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality. A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013. Nutrient intake in the s le largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance. This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy s les, but limitations must be noted regarding comparability. Future studies employing larger s le sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.
Publisher: SAGE Publications
Date: 24-06-2013
Abstract: Prevention strategies have made a major contribution to the considerable successes in reductions in cardiovascular disease and cancer mortality seen in recent decades. However, in the field of psychiatry, similar population-level initiatives in the prevention of common mental disorders, depression and anxiety, are noticeably lacking. This paper aims to provide a brief overview of the existing literature on the topic of the prevention of common mental disorders and a commentary regarding the way forward for prevention research and implementation. This commentary considers what we currently know, what we might learn from the successes and failures of those working in prevention of other high prevalence health conditions, and where we might go from here. Taking cognisance of previous preventive models, this commentary additionally explores new opportunities for preventive approaches to the common mental disorders. The consensus from a large body of evidence supports the contention that interventions to prevent mental disorders across the lifespan can be both effective and cost-effective. However, funding for research in the area of prevention of common mental disorders is considerably lower than that for research in the areas of treatment, epidemiology and neurobiology. Thus, there is a clear imperative to direct funding towards prevention research to redress this imbalance. Future prevention interventions need to be methodologically rigorous, scalable to the population level and include economic evaluation. Evidence-based knowledge translation strategies should be developed to ensure that all stakeholders recognise preventing mental disorders as an imperative, with appropriate resources directed to this objective. There has been a recent expansion of research into potentially modifiable risk factors for depression, and it is now timely to make a concerted effort to advance the field of prevention of common mental disorders.
Publisher: Physicians Postgraduate Press, Inc
Date: 15-06-2014
DOI: 10.4088/JCP.13M08454
Publisher: Elsevier BV
Date: 08-2021
Publisher: Wiley
Date: 04-08-2008
DOI: 10.1111/J.1600-0447.2008.01230.X
Abstract: Evidence related to overlapping clinical and genetic risk factors in schizophrenia and bipolar disorder (BD) have raised concerns about the validity of 'Kraepelinian dichotomy'. As controversies mainly arise in mixed psychoses that occupy the intermediate zone between schizophrenia and BD, investigating neurobiological markers of mixed psychoses may be relevant to understanding the nature of psychotic disorders. In this article, we review studies comparing magnetic resonance imaging, neuropsychological and electrophysiological findings in mixed psychoses with each other, as well as with more prototypical cases of schizophrenia and BD. The evidence reviewed suggests that mixed psychoses may be associated with different genetic and neurobiological markers compared with prototypical forms of schizophrenia and BD. These findings may be compatible with more sophisticated versions of dimensional and continuum models or, alternatively, they may suggest that there is an intermediate third category between prototypical schizophrenia and BD.
Publisher: Informa UK Limited
Date: 16-09-2021
Publisher: Springer Science and Business Media LLC
Date: 10-09-2019
DOI: 10.1186/S13063-019-3628-5
Abstract: Tobacco smoking is a highly prevalent, addictive behaviour and a key public health priority. However available cessation therapies have low quit and high relapse rates, indicating an urgent need for more effective treatments. Predicated on promising preclinical and pilot clinical data, this paper presents a rationale and protocol for the trial of N-acetylcysteine (NAC) as a novel anti-craving smoking cessation aid. Current smokers ( n = 120) of at least 10 cigarettes a day are recruited through online advertisements, print publications and dissemination of flyers. Participants are randomised on a 1:1 ratio to receive either 16-week treatment of 1.8 g/day of NAC or placebo with all participants receiving quit support from the online QuitCoach tool. Participants are attending visits at baseline, 8 and 16 weeks with a 42-week post-discontinuation follow-up. The primary outcome measure is sustained abstinence at six months after treatment based on self-reported rating scales and confirmed by exhaled carbon monoxide and salivary cotinine levels. Secondary outcomes are timing of the first lapse and relapse, between-group cigarette consumption, withdrawal symptoms, general wellbeing and mood/anxiety symptoms. Between-group differences in adverse events and subgroup analyses for variables including gender and Diagnostic Statistics Manual 5 diagnostics will also be investigated. The planned trial addresses an issue of major importance to human health and, if an effect is shown, may result in substantial changes to the management of smoking and nicotine addiction with overt public health implications. Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12617001478303 . Registered on 19 October 2017.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2011
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000444646
Publisher: Bentham Science Publishers Ltd.
Date: 08-2009
DOI: 10.2174/092986709788803060
Abstract: The tripeptide, glutathione (gamma-glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.
Publisher: Royal College of Psychiatrists
Date: 06-2017
DOI: 10.1192/BJP.BP.116.186833
Abstract: Lithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other. To investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania. Maintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry – ACTRN12607000639426.) In total, 61 in iduals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine. In people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution.
Publisher: Informa UK Limited
Date: 16-10-2019
Publisher: Massachusetts Medical Society
Date: 03-01-2019
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.PSYCHRES.2015.01.021
Abstract: This study aimed to investigate the association of obsessive-compulsive symptoms with clinical and neurocognitive features in patients with schizophrenia. This study enrolled 163 people with schizophrenia who were receiving risperidone monotherapy. Comorbid obsessive-compulsive symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale, and subjects with a score ≥ 10 constituted the obsessive-compulsive symptom group (n=30, 18.4%). The learning index was significantly higher in patients with obsessive-compulsive symptoms than in those without such symptoms after adjusting for age, stage (early and chronic), duration of illness, and CDSS score. However, there was no significant interaction between obsessive-compulsive symptoms and stage of illness. Scores on Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Beck Depression Inventory were significantly higher in the obsessive-compulsive symptom group. In addition, the Subjective Well-being under Neuroleptic Treatment score was significantly lower in the obsessive-compulsive symptom group. In conclusion, comorbid obsessive-compulsive symptoms in patients with schizophrenia were associated with a higher learning ability without a significant interaction with stage of illness. However, schizophrenia patients with obsessive-compulsive symptoms had more severe psychotic and depressive symptoms and poorer quality of life.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S13063-021-05812-6
Abstract: Beta-casein is a major protein in cow’s milk, of which A1 and A2 are the most frequent variants. Recent evidence implicates A1 beta-casein consumption in mechanisms that are of potential importance to mental health, yet its possible effects on psychological endpoints remains unknown. The primary aim of the study is to evaluate the comparative effects of consumption of dairy products containing A2 beta-casein versus conventional dairy (i.e. containing both A1 and A2 beta-casein) on symptoms of psychological distress in women with low mood. ‘The Moo’D Study’ is a 16-week, superiority, 1:1 parallel group, triple-blinded, randomised controlled trial. Ninety women with low mood (Patient Health Questionnaire score ≥ 5) will be randomised to consume either A2 beta-casein only or conventional dairy products. The primary outcome, symptoms of psychological distress, will be measured by the 21-item Depression, Anxiety and Stress Scale. Secondary outcomes will include symptoms of depression, anxiety and stress, severity of low mood, cognition, gut microbiota composition, gut symptomatology, markers of immune function, gut inflammation, systemic metabolites, endothelial integrity and oxidative stress, body composition, perceived wellbeing, sleep, quality of life, resource use and cost-effectiveness. This study will advance our understanding of the possible impact of milk proteins on psychological distress in women as well as elucidate mechanisms underpinning any association. Given dairy products form a substantial component of traditional and Western diets, the implications of these findings are likely to be of clinical and public health importance. The trial protocol has been prospectively registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12618002023235. Registered on 17 December 2018.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2012
Publisher: Elsevier BV
Date: 09-2019
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.NEUBIOREV.2017.07.017
Abstract: There is a wealth of data indicating that de novo protein S-nitrosylation in general and protein transnitrosylation in particular mediates the bulk of nitric oxide signalling. These processes enable redox sensing and facilitate homeostatic regulation of redox dependent protein signalling, function, stability and trafficking. Increased S-nitrosylation in an environment of increasing oxidative and nitrosative stress (O&NS) is initially a protective mechanism aimed at maintaining protein structure and function. When O&NS becomes severe, mechanisms governing denitrosylation and transnitrosylation break down leading to the pathological state referred to as hypernitrosylation (HN). Such a state has been implicated in the pathogenesis and pathophysiology of several neuropsychiatric and neurodegenerative diseases and we investigate its potential role in the development and maintenance of neuroprogressive disorders. In this paper, we propose a model whereby the hypernitrosylation of a range of functional proteins and enzymes lead to changes in activity which conspire to produce at least some of the core abnormalities contributing to the development and maintenance of pathology in these illnesses.
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2023
Publisher: Physicians Postgraduate Press, Inc
Date: 30-06-2009
DOI: 10.4088/JCP.08R04472
Publisher: Royal College of Psychiatrists
Date: 09-2010
Publisher: SAGE Publications
Date: 2009
DOI: 10.1080/00048670902873706
Abstract: Objective: The Mood Disorder Questionnaire (MDQ) is a widely used self-report screening instrument for the detection of bipolar disorder in clinical populations. The aim of the present study was therefore to investigate the reliability of this instrument. Methods: Screening results using the MDQ were compared with results obtained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID) in a community-based s le of 1066 women. Trained personnel, who were blind to the results of the MDQ screen, conducted clinical interviews. Results: Using the MDQ, 21 women screened positive for bipolar disorder, and using the SCID diagnoses, 24 women were confirmed with a diagnosis of bipolar disorder. Six women were detected on both instruments. Compared to the SCID, the sensitivity for the MDQ was 25%, specificity 99%, positive predictive value 28%, negative predictive value 98%, and a demonstrated kappa of 0.25. The MDQ failed to detect any of the 11 participants in the study with bipolar II disorder and missed seven of 13 participants with bipolar I disorder or bipolar not otherwise specified. Of the 21 women who screened positive using the MDQ, 19 had current or past psychopathologies other than bipolar disorder. Conclusion: The MDQ has substantial limitations for detection of bipolar disorder, in particular bipolar II disorder, in non-clinical populations.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JAD.2021.09.103
Abstract: The influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder was systematically reviewed. Randomised and non-randomised studies of interventions for bipolar disorder that included an assessment of childhood trauma were eligible. MEDLINE Complete, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched. Two independent reviewers completed the screening and extraction process. Two independent reviewers assessed the risk of bias in the included studies using the Cochrane Collaboration's Risk of Bias tool and the Newcastle-Ottawa Scale. Alongside a narrative synthesis, random-effects meta-analyses were performed. Twelve studies (1175 participants) were included. The narrative review highlighted differential treatment outcomes among in iduals with a history of childhood trauma. The meta-analyses suggested that childhood trauma was unrelated to treatment response (five studies, 426 participants odds ratio 0.58, 95% CI 0.27-1.25, p = .164) but may be associated with greater improvement in global functioning (three studies, 210 participants Hedge's g 0.65, 95% CI 0.04-1.26, p = .037). The impact of childhood trauma on the effectiveness of specific pharmacological sychological interventions could not be explored due to the small body of research identified. The overall quality of the extant evidence is low, which precludes definitive comment on the role of childhood trauma in the treatment of bipolar disorder. Additional research that uses large and representative s les is required to ascertain whether a history of childhood trauma affects the treatment outcomes of interventions for in iduals with bipolar disorder.
Publisher: Wiley
Date: 10-02-2019
DOI: 10.1111/EIP.12797
Abstract: Young people with bipolar disorder (BD) commonly experience reduced quality of life, persistent symptoms and impaired functional recovery despite often superior school performance. Compromised long-term functioning can ensue. There is evidence that psychological therapies alongside pharmacology may be more efficacious earlier in the course of the disorder. Intervention in the early stages may thus reduce the burden and risk associated with BD and mitigate the impact of the disorder on normal developmental trajectories. To date, however, the availability of evidence-based psychological therapies for young people with early BD is limited. Furthermore, there are no large-scale randomized controlled trials (RCTs) of such interventions. The study is a prospective, single-blind, RCT examining the effectiveness of an adjunctive in idualized and manualized psychological intervention, compared with treatment as usual within youth-specific early intervention services. The REsearch into COgnitive and behavioural VERsatility (RECOVER) intervention is delivered over a 6-month period. About 122 young people in the early stages of BD-I (at least one manic episode in the previous 2 years, with no more than five lifetime treated/untreated manic or hypomanic episodes) will be recruited. The assessments will occur at baseline, 3, 6 (primary endpoint, end of treatment), 9, 12, 15 and 18 months. Recruitment will commence in January 2019 and is anticipated to occur over a 3.5-year period. To date, there are no evidence-based psychological therapies tailored to young people with early BD. We will test whether early psychological intervention in the course of BD can reduce the symptomatic, psychological, vocational and social impacts that are seen in entrenched disorder.
Publisher: Wiley
Date: 08-05-2019
DOI: 10.1002/GPS.5119
Publisher: Springer Science and Business Media LLC
Date: 11-02-2021
DOI: 10.1186/S12891-021-04042-W
Abstract: Anticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based s le of men and women. Data from 926 men (24-73 yr) and 1070 women (21-94 yr) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm 2 ) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders. Seventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. In women, BMD tended to be lower at the hip compared to non-users as with the bone quality measure, BUA. No significant associations were observed at the spine or the other bone quality measures, SOS and SI. Our data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.
Publisher: AMPCo
Date: 10-2012
DOI: 10.5694/MJAO12.10611
Publisher: JMIR Publications Inc.
Date: 11-07-2016
DOI: 10.2196/MENTAL.5475
Abstract: Although physical illnesses, routinely documented in electronic medical records (EMR), have been found to be a contributing factor to suicides, no automated systems use this information to predict suicide risk. The aim of this study is to quantify the impact of physical illnesses on suicide risk, and develop a predictive model that captures this relationship using EMR data. We used history of physical illnesses (except chapter V: Mental and behavioral disorders) from EMR data over different time-periods to build a lookup table that contains the probability of suicide risk for each chapter of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes. The lookup table was then used to predict the probability of suicide risk for any new assessment. Based on the different lengths of history of physical illnesses, we developed six different models to predict suicide risk. We tested the performance of developed models to predict 90-day risk using historical data over differing time-periods ranging from 3 to 48 months. A total of 16,858 assessments from 7399 mental health patients with at least one risk assessment was used for the validation of the developed model. The performance was measured using area under the receiver operating characteristic curve (AUC). The best predictive results were derived (AUC=0.71) using combined data across all time-periods, which significantly outperformed the clinical baseline derived from routine risk assessment (AUC=0.56). The proposed approach thus shows potential to be incorporated in the broader risk assessment processes used by clinicians. This study provides a novel approach to exploit the history of physical illnesses extracted from EMR (ICD-10 codes without chapter V-mental and behavioral disorders) to predict suicide risk, and this model outperforms existing clinical assessments of suicide risk.
Publisher: Cambridge University Press (CUP)
Date: 10-2010
DOI: 10.1111/J.1601-5215.2010.00472.X
Abstract: Berk M, Dodd S, Dean OM, Kohlmann K, Berk L, Malhi GS. The validity and internal structure of the Bipolar Depression Rating Scale: data from a clinical trial of N-acetylcysteine as adjunctive therapy in bipolar disorder. The phenomenology of unipolar and bipolar disorders differ in a number of ways, such as the presence of mixed states and atypical features. Conventional depression rating instruments are designed to capture the characteristics of unipolar depression and have limitations in capturing the breadth of bipolar disorder. The Bipolar Depression Rating Scale (BDRS) was administered together with the Montgomery Asberg Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in a double-blind randomised placebo-controlled clinical trial of N-acetyl cysteine for bipolar disorder ( N = 75). A factor analysis showed a two-factor solution: depression and mixed symptom clusters. The BDRS has strong internal consistency (Cronbach's alpha = 0.917), the depression cluster showed robust correlation with the MADRS ( r = 0.865) and the mixed subscale correlated with the YMRS ( r = 0.750). The BDRS has good internal validity and inter-rater reliability and is sensitive to change in the context of a clinical trial.
Publisher: Springer Science and Business Media LLC
Date: 23-11-2021
DOI: 10.1038/S41380-020-00951-9
Abstract: The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.
Publisher: Oxford University Press (OUP)
Date: 2020
DOI: 10.1093/SCHIZBULLOPEN/SGAA015
Abstract: This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP. Trial Registration: ACTRN12607000608460 (www.anzctr.org.au).
Publisher: Springer Science and Business Media LLC
Date: 19-10-2012
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.BIOPSYCH.2008.03.004
Abstract: Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and refractory to treatment. N-acetyl cysteine (NAC) increases brain glutathione in rodents. This study was conducted to evaluate the safety and effectiveness of oral NAC (1 g orally twice daily [b.i.d.]) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period. A randomized, multicenter, double-blind, placebo-controlled study. The primary readout was change from baseline on the Positive and Negative Symptoms Scale (PANSS) and its components. Secondary readouts included the Clinical Global Impression (CGI) Severity and Improvement scales, as well as general functioning and extrapyramidal rating scales. Changes following a 4-week treatment discontinuation were evaluated. One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were randomized 84 completed treatment. Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [-5.97 (-10.44, -1.51), p = .009], PANSS negative [mean difference -1.83 (95% confidence interval: -3.33, -.32), p = .018], and PANSS general [-2.79 (-5.38, -.20), p = .035], CGI-Severity (CGI-S) [-.26 (-.44, -.08), p = .004], and CGI-Improvement (CGI-I) [-.22 (-.41, -.03), p = .025] scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia (p = .022). Effect sizes at end point were consistent with moderate benefits. These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.PNPBP.2011.11.011
Abstract: Bipolar disorder (BD) is intricately associated with chronic clinical conditions. Medical comorbidity is not only more prevalent in mood disorders, but is associated with increased costs, cognitive impairment and, ultimately, premature mortality. Oxidative stress and inflammation may mediate part of this association. To further investigate the association between medical comorbidity status and clinical improvement with adjuvant N acetyl cysteine (NAC) in the context of a placebo-controlled trial. Placebo-controlled randomized clinical trial assessing the effect of NAC over 24 weeks. Symptomatic and functional outcomes were collected over the study period. Medical comorbidities were self-reported, and we took special interest in cardiovascular and endocrine conditions. We evaluated change from baseline to endpoint and the interaction between change and reported medical comorbidities. Fifty-one percent of patients reported have a cardiovascular or endocrine comorbidity. Although not found for depressive symptoms or quality of life, a significant interaction between medical comorbidity and change scores was consistently found for all functional outcomes. This indicated an advantage of NAC over placebo in those with a clinical comorbidity. Systemic illness moderated only the effect of NAC on functioning, not on depression. Demonstrating an improvement in functional outcomes with an agent that modulates redox and inflammatory pathways, this study lends empirical support to the idea that medical and psychiatric comorbidity are additive in contributing to allostatic states. One intriguing possibility is that comorbid clinical illness could be a marker for more severe oxidative stress states--and thus guide antioxidant use--in BD.
Publisher: American Chemical Society (ACS)
Date: 28-01-2011
DOI: 10.1021/JP110762S
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 09-05-2014
Publisher: Informa UK Limited
Date: 03-03-2021
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 09-01-2023
DOI: 10.1186/S40814-023-01235-Z
Abstract: Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD. This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial ( n = 15), of enema-delivered FMT treatment ( n = 10) compared with a placebo enema ( n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters. Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need. Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864
Publisher: Springer Science and Business Media LLC
Date: 12-02-0003
DOI: 10.1038/MP.2013.7
Abstract: The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA(2)) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the in iduals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA(2) and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA(2) were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA(2) activity were in opposite directions in in iduals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA(2) activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA(2) activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.
Publisher: Wiley
Date: 23-07-2023
DOI: 10.5694/MJA2.52047
Publisher: Cambridge University Press (CUP)
Date: 29-11-2016
DOI: 10.1017/S0033291716002932
Abstract: Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N -acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder. A s le of 58 participants were randomized in a double fashion to receive 2 g/day of NAC ( n = 27) or placebo ( n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann–Whitney test was used to examine the differences between the NAC and placebo groups at the end point. Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo ( U = 98.5, p = 0.027). NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.
Publisher: SAGE Publications
Date: 11-08-2022
DOI: 10.1177/00048674221115641
Abstract: To measure symptoms of anxiety, depression and hopelessness in a s le of young Pacific adults living in Auckland, New Zealand during the 2020/2021 COVID-19 pandemic and identify protective factors. Participants were 267 Pacific adults (58% female) who completed a survey online. Analyses included descriptive statistics, correlations, linear regression and symptom network analysis. Around 25% of the s le scored in the range for moderate to severe anxiety and 10% for moderate to severe depression on standard measures. Almost 40% indicated that they found the first lockdown very stressful and 55% noted that some members of their family found it stressful. Only 16% worried about COVID-19 and their future quite a bit or constantly, while another 25% worried sometimes. Self-compassion and Pacific Identity had moderate, negative correlations, and Worry about COVID-19 had weak positive correlations, with anxiety, depression, hopelessness and perceived stress. These results suggest that, while the prevalence of depression and anxiety are quite high among this population, fostering ethnic identity and self-compassion in Pacific children and adolescents might protect against developing depression and anxiety.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2009
Publisher: SAGE Publications
Date: 04-08-2022
DOI: 10.1177/00048674221115644
Abstract: Childhood trauma is negatively associated with depression severity in bipolar disorder however, the underlying mechanisms remain unclear. We investigated whether personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) mediate the relationship between childhood trauma and the severity of bipolar depression. Data from 209 in iduals with bipolar disorder recruited for the Prechter Longitudinal Study of Bipolar Disorder were analysed. Using structural equation modelling, we examined the direct and indirect associations between childhood trauma (Childhood Trauma Questionnaire) and depression severity (Hamilton Depression Rating Scale) - with the personality traits (NEO Personality Inventory-Revised) as mediators. The direct effect of childhood trauma on depression severity (standardised β = 0.32, 95% bootstrap confidence interval [CI] = 0.20-0.45, Personality traits may be relevant psychological mediators that link childhood trauma to a more severe clinical presentation of bipolar depression. Consequently, a person's personality structure may be a crucial operative factor to incorporate in therapeutic plans when treating in iduals with bipolar disorder who report a history of childhood trauma.
Publisher: MDPI AG
Date: 28-06-2022
DOI: 10.3390/IJMS23137180
Abstract: Altered protein synthesis has been implicated in the pathophysiology of several neuropsychiatric disorders, particularly schizophrenia. Ribosomes are the machinery responsible for protein synthesis. However, there remains little information on whether current psychotropic drugs affect ribosomes and contribute to their therapeutic effects. We treated human neuronal-like (NT2-N) cells with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM) or vehicle control for 24 h. Transcriptomic and gene set enrichment analysis (GSEA) identified that the ribosomal pathway was altered by these drugs. We found that three of the eight drugs tested significantly decreased ribosomal gene expression, whilst one increased it. Most changes were observed in the components of cytosolic ribosomes and not mitochondrial ribosomes. Protein synthesis assays revealed that aripiprazole, clozapine and lithium all decreased protein synthesis. Several currently prescribed psychotropic drugs seem to impact ribosomal gene expression and protein synthesis. This suggests the possibility of using protein synthesis inhibitors as novel therapeutic agents for neuropsychiatric disorders.
Publisher: Public Library of Science (PLoS)
Date: 24-09-2014
Publisher: Korean Neuropsychiatric Association
Date: 2015
Publisher: Informa UK Limited
Date: 24-05-2022
Publisher: American Medical Association (AMA)
Date: 09-2016
DOI: 10.1001/JAMAPSYCHIATRY.2016.1383
Abstract: A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects. To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia. This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis. Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed. Of the 56 participants (mean [SD] age, 53 [7.7] years age range, 40-70 years mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37 95% CI, -11.64 to -1.10 P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79 95% CI, 1.46 to 22.97 P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72 95% CI, -6.83 to -0.61 P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92 95% CI, -3.83 to 0.00 P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups. Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice. clinicaltrials.gov Identifier: NCT00361543.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2020
DOI: 10.1186/S12916-019-1475-6
Abstract: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15–25 years). YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15–25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0 N = 130 age 20.2 ± 2.6 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin ( n = 40), rosuvastatin ( n = 48), or placebo ( n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (− 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (− 4.2, 95% CI (− 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. Australian New Zealand Clinical Trials Registry, ACTRN12613000112763 . Registered on 30/01/2013.
Publisher: Elsevier BV
Date: 11-2020
Publisher: SAGE Publications
Date: 02-2012
Abstract: Background: The concept of staging of disease in psychiatry has developed over the past years. A neglected component of this model pertains to people in the advanced stages of a mental illness, who remain symptomatic and functionally impaired despite treatment. These patients are often high service utilizers, receiving complex multimodal treatments where the balance of risk and benefit shifts perceptibly. In this paper, we argue the need to adopt ‘palliative’ models of care for some in iduals, and consider changing the therapeutic goals to follow care pathways similar to those used in other chronic and refractory medical illnesses. Method: Data was sourced by a literature search using Medline and a hand search of scientific journals. Relevant articles were selected. Results: Clinical staging can help us better define subgroups of patients who will benefit from different goals and treatment. In the most advanced stage group, we find patients with persistent symptoms and treatment resistance. In these situations, it may be preferable to follow some of the principles of palliative care, which include the setting of attainable goals, reduction of side-effects, limited symptom control, targeting identified psychological and social problems, and attempting to attain the best quality of life for these patients and their families. Conclusions: It is in the interest of those in the advanced phases of a disorder that clinicians acknowledge the limitations of treatment and actively attempt to plan treatment utilizing alternate models. It is essential to be clear that such approaches do not equate to the abandonment of care, but rather to the reconceptualizing of feasible and personalized treatment goals, a rebalancing of the risks and benefits of intervention, the management of illness behaviour, and the approaches that allow the patient to live gainfully within their limitations.
Publisher: Royal College of Psychiatrists
Date: 05-2017
DOI: 10.1192/BJP.BP.116.195321
Abstract: Few trials have compared psychosocial therapies for people with bipolar affective disorder, and conventional meta-analyses provided limited comparisons between therapies. To combine evidence for the efficacy of psychosocial interventions used as adjunctive treatment of bipolar disorder in adults, using network meta-analysis (NMA). Systematic review identified studies and NMA was used to pool data on relapse to mania or depression, medication adherence, and symptom scales for mania, depression and Global Assessment of Functioning (GAF). Carer-focused interventions significantly reduced the risk of depressive or manic relapse. Psychoeducation alone and in combination with cognitive–behavioural therapy (CBT) significantly reduced medication non-adherence. Psychoeducation plus CBT significantly reduced manic symptoms and increased GAF. No intervention was associated with a significant reduction in depression symptom scale scores. Only interventions for family members affected relapse rates. Psychoeducation plus CBT reduced medication non-adherence, improved mania symptoms and GAF. Novel methods for addressing depressive symptoms are required.
Publisher: SAGE Publications
Date: 28-11-2019
Abstract: In iduals with bipolar disorder (BD) generally engage in low levels of physical activity (PA), and yet few studies have investigated the relationship between PA and change in BD symptom severity. The aim of this subanalysis of an adjunctive nutraceutical randomized controlled trial for the treatment of bipolar depression was to explore the relationship between PA, the active adjunctive treatments (a nutraceutical “mitochondrial cocktail”), and clinical outcomes. Participants with bipolar depression were randomized to receive N-acetylcysteine alone, N-acetylcysteine with a combination of nutraceuticals (chosen for the potential to increase mitochondrial activity), or placebo for 16 weeks. Participants ( n = 145) who completed the International Physical Activity Questionnaire–Short Form (IPAQ-SF measured at Week 4) were included in this exploratory subanalysis. Assessments of BD symptoms, functioning, and quality of life were completed at monthly visits up until Week 20. Generalised Estimating Equations were used to explore whether IPAQ-SF scores were a moderator of treatment received on outcomes of the study. Week-4 PA was not related to changes in Montgomery Åsberg Depression Rating Scale scores across the study until Week 20. However, participants who engaged in more PA and who received the combination treatment were more likely to have a reduction in scores on the Bipolar Depression Rating Scale ( P = 0.03). However, this was not consistent in all domains explored using the IPAQ-SF. Participants who engaged in higher levels of PA also experienced greater improvement in social and occupational functioning and less impairment in functioning due to their psychopathology and improvement in quality of life at Week 20, irrespective of treatment. This study provides novel evidence of the association between PA and reduction in BD symptoms in a nutraceutical clinical trial. However, further research assessing the potential synergistic effects of PA in BD is required.
Publisher: Wiley
Date: 02-2011
DOI: 10.1111/J.1399-5618.2011.00889.X
Abstract: The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention. Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. In iduals were categorized as having had 0, 1-5, 6-10, or >10 prior episodes of illness, and data were analyzed across these groups. Response rates for the mania and maintenance studies ranged from 52-69% and 10-50%, respectively, for in iduals with 1-5 previous episodes, and from 29-59% and 11-40% for in iduals with >5 previous episodes. These rates were significantly higher for the 1-5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1-5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40-60% for those who had experienced 1-5 episodes or 6-10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1-5 episode group (p=0.005). Those in iduals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and underscores the need to support a policy of early intervention.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 09-2015
DOI: 10.1007/S40263-015-0272-9
Abstract: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. The aim of this study was to assess the efficacy and safety of NAC in treating OCD. A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. Analysis of the full s le (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score (p = 0.15). However, a significant time × treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20%) participants were considered 'responders' (YBOCS ≥35% reduction at endpoint) versus four (27%) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). Further research involving NAC for OCD may require larger s les to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. ACTRN12613000310763.
Publisher: Wiley
Date: 12-05-2006
DOI: 10.1111/J.1399-5618.2006.00315.X
Abstract: Recent studies have shown that outcome in mania is worse than previously thought. Such studies have been conducted in selected s les with restrictive measures of outcome. We aimed to explore outcome and its predictors in a catchment area s le of first-episode psychotic mania of DSM-III-R bipolar I disorder. Prospective 6 and 12 months follow-up was conducted with 87 DSM-III-R first-episode psychotic mania patients admitted to Early Psychosis Prevention and Intervention Centre between 1989 and 1997. Syndromic and symptomatic outcome were determined with the Brief Psychiatric Rating Scale functional outcome with the Quality of Life Scale and Premorbid Adjustment Scale subitems. Symptomatic outcome was assessed in 67 patients at 6 months and 61 patients at 12 months, and functional outcome in 56 patients at 6 months and 49 patients at 12 months. Logistic regressions were conducted on 46 and 43 patients, respectively, to explore predictors of outcome. While 90% of patients achieved syndromic recovery at 6 and 12 months, 40% had not recovered symptomatically at 6 and 12 months, still presenting with anxiety or depression. A total of 66% of patients at 6 months and 61% of patients at 12 months failed to return to previous level of functioning. Age at intake, family history of affective disorder, illicit drug use and functional recovery at 6 months predicted functional outcome at 12 months. This study confirms poor symptomatic and functional outcome after first-episode psychotic mania. It suggests possible usefulness of early intervention strategies in bipolar disorders and need for developing specific interventions addressing anxiety, depression and substance abuse comorbidity.
Publisher: Cambridge University Press (CUP)
Date: 04-2006
DOI: 10.1111/J.1601-5215.2006.00130.X
Abstract: Depression and pain are both burdensome ailments that affect a major proportion of the population. It is evident that depression and pain frequently coexist, with treatment and outcome implications. To review the literature on the nature, prevalence and co-morbidity of depression and pain, the biological and psychological mechanisms involved and treatment options, thus presenting a broad overview of the current information available. Relevant sources were identified from PubMed and Medline databases using a combination of keywords including depression, pain, prevalence, co-morbidity, biological and psychological mechanisms, serotonin (5-HT), norepinephrine (NE), hypothalamic-pituitary-adrenal (HPA) axis, amygdala, functional magnetic resonance imaging (fMRI), antidepressant and psychological therapy. It is evident from the research that depression and pain are common co-morbidities. Pain as a physical symptom of depression affects approximately 65% of patients, leading to less favourable outcomes and greater health care utilization. Moreover, depression is a common feature in chronic pain patients and can affect pain threshold and tolerance. Evidence from biological and psychological studies has revealed mechanisms that link chronic pain to depression. Several classes of anti-depressants and psychological interventions have been used successfully in the treatment of somatic symptoms of depression and for a variety of pain syndromes. Pain and depression are linked by overlapping phenomenology, neurobiology and therapy. They are mutually interacting, and the interaction has significant treatment and outcome implications.
Publisher: Wiley
Date: 06-10-2020
DOI: 10.1111/DAR.13183
Abstract: There has been a rapid increase in smoking crystalline meth hetamine in Australia. We compare the clinical and demographic characteristics of those who smoke versus inject the drug in a cohort of people who use meth hetamine. Participants ( N = 151) were dependent on meth hetamine, aged 18–60 years, enrolled in a pharmacotherapy trial for meth hetamine dependence, and reported either injecting ( n = 54) or smoking ( n = 97) meth hetamine. Measures included the Timeline Followback, Severity of Dependence Scale, Amphetamine Withdrawal Questionnaire, Craving Experience Questionnaire and the Brief Psychiatric Rating Scale (symptoms of depression, hostility, psychosis and suicidality). Simultaneous regression was used to identify independent demographic correlates of smoking meth hetamine and to compare the clinical characteristics of participants who smoked versus injected. Compared to participants who injected meth hetamine, those who smoked meth hetamine were younger and less likely to be unemployed, have a prison history or live alone. Participants who smoked meth hetamine used meth hetamine on more days in the past 4 weeks than participants who injected meth hetamine (26 vs. 19 days, P = 0.001) they did not differ significantly in their severity of meth hetamine dependence, withdrawal, craving or psychiatric symptoms ( P 0.05). After adjustment for demographic differences, participants who smoked had lower craving [b (SE) = −1.1 (0.5), P = 0.021] and were less likely to report psychotic symptoms [b (SE) = −1.8 (0.7), P = 0.013] or antidepressant use [b (SE) = −1.1 (0.5), P = 0.022]. Smoking crystalline meth hetamine is associated with a younger less marginalised demographic profile than injecting meth hetamine, but a similarly severe clinical profile.
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/15622970410029924
Abstract: As with the two preceding guidelines of this series, these practice guidelines for the pharmacological maintenance treatment of bipolar disorder were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence relating to maintenance treatment. The data used for these guidelines were extracted from a MEDLINE and EMBASE search, from recent proceedings from key conferences and various national and international treatment guidelines. The scientific justification of support for particular treatments was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also reviewed by the experts of the task force to ensure practicality.
Publisher: ACM
Date: 11-08-2013
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.JAD.2008.03.024
Abstract: While ECT is widely used for the management of severe and refractory depression, its utility in bipolar disorder is not extensively studied. The aim of this study was to examine the reported effectiveness of ECT in patients with unipolar and bipolar depression as reported by psychiatrists, nurses and patients (i.e. using objective and subjective measures). The records of 787 consecutive inpatient admissions to the Geelong Clinic, a private psychiatric centre based outside Melbourne, Victoria were reviewed in this file audit. Routine assessment measures were completed at admission and discharge, and included patient rated measures (Medical Outcomes Short Form SF-14 and Depression Anxiety and Stress Scale, DASS), nurse rated measures, (The Health of the Nation Outcome Scale, HoNOS) and a psychiatrist rated measure, the Clinical Global impression scale (CGI). In contrast to in iduals with unipolar depression, where improvement was seen on all measures, in bipolar disorder, while improvement in clinician rated measures was seen (CGI, HoNOS), there was an absence of improvement in subjective measures of mood (DASS, SF14). This study suggests that in bipolar disorder, there is a poorer subjective response to ECT than in unipolar disorder.
Publisher: Oxford University Press (OUP)
Date: 27-03-2018
DOI: 10.1093/IJNP/PYY018
Publisher: Springer Science and Business Media LLC
Date: 22-05-2018
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JAD.2019.07.062
Abstract: Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.
Publisher: Oxford University Press (OUP)
Date: 19-02-2018
DOI: 10.1093/IJNP/PYY014
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 25-10-2016
DOI: 10.1111/INM.12267
Abstract: Patient safety research focussing on recognizing and responding to clinical deterioration is gaining momentum in generalist health, but has received little attention in mental health settings. The focus on early identification and prompt intervention for clinical deterioration enshrined in patient safety research is equally relevant to mental health, especially in triage and crisis care contexts, yet the knowledge gap in this area is substantial. The present study was a controlled cohort study (n = 817) that aimed to identify patient and service characteristics associated with clinical deterioration of mental state indicated by unplanned admission to an inpatient psychiatric unit following assessment by telephone-based mental health triage. The main objective of the research was to produce knowledge to improve understandings of mental deterioration that can be used to inform early detection, intervention, and prevention strategies at the point of triage. The results of the study found that the clinical profile of admitted patients was one of complexity and severity. Admitted patients were more likely to have had complex psychiatric histories with multiple psychiatric admissions, severe psychotic symptoms, a history of treatment non-adherence, and poorer social functioning than non-admitted patients.
Publisher: Public Library of Science (PLoS)
Date: 10-03-2016
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JAD.2014.05.055
Abstract: To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months. Secondary analysis was performed on data collected during an 8-week RCT comparing the efficacy of olanzapine versus chlorpromazine as an adjunct to lithium, and at 18-month follow-up. 74 participants were ided into three groups (no insight, partial insight, and full insight) according to the insight item from the Young Mania Rating Scale (YMRS). Differences between these three groups were examined at baseline and at 18 months on measures of symptoms (YMRS, HAMD-21, and CGI-S), and social and occupational functioning (SOFAS). Baseline differences between the three groups were determined using general linear models and chi-squared analyses. Group differences from baseline to 18-month follow-up were determined using repeated measures general linear models. At baseline there were significant differences between the three insight groups in terms of mania and functioning, but at 18 months all groups had improved significantly in terms of psychopathology, mania, depression and social and occupational functioning. There were no significant differences between the three groups at study completion with respect to these domains. The study was limited by the lack of availability of a more detailed rating scale for insight, and it did not account for the duration of untreated psychosis (DUI). Poor initial insight during a first episode of mania with psychotic features does not predict poor clinical and psychosocial outcome at 18 months.
Publisher: Wiley
Date: 16-04-2013
DOI: 10.1111/ACPS.12124
Abstract: To be used in conjunction with 'Pharmacological management of unipolar depression' [Malhi et al. Acta Psychiatr Scand 2013 (Suppl. 443):6-23] and 'Psychological management of unipolar depression' [L e et al. Acta Psychiatr Scand 2013 (Suppl. 443):24-37]. To provide clinically relevant recommendations for lifestyle modifications in depression, derived from a literature review. A search of pertinent literature was conducted up to August 2012 in the area of lifestyle factors and depression. A narrative review was then conducted. There is evidence that level of physical activity plays a role in the risk of depression, and there is a large and validated evidence base for exercise as a therapeutic modality. Smoking and alcohol and substance misuse appear to be independent risk factors for depression, while the new epidemiological evidence supports the contention that diet is a risk factor for depression good quality diets appear protective and poor diets increase risk. Lifestyle modification, with a focus on exercise, diet, smoking and alcohol, may be of substantial value in reducing the burden of depression in in iduals and the community.
Publisher: Informa UK Limited
Date: 07-2009
DOI: 10.1586/ERN.09.31
Abstract: A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: in iduals who present mood and anxiety symptoms and increased risk for developing threshold BD Stage I--patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes Stage II--patients who present rapid cycling or current axis I or II comorbidities Stage III--patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers and Stage IV--patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.
Publisher: Wiley
Date: 06-2017
DOI: 10.1111/BDI.12502
Publisher: Wiley
Date: 27-04-2011
DOI: 10.1111/J.1751-7893.2011.00273.X
Abstract: This paper will describe the rationale for, and importance of, psychological interventions for young people early in the course of bipolar disorder. Emerging literature in this field will be discussed in addition to describing specific clinical challenges and opportunities with this population. In order to be more developmentally appropriate for young people with bipolar disorder, eight aspects of clinical work which may require modification were identified. The evidence base for the effectiveness of psychological interventions for people diagnosed with bipolar disorder is growing. However, some aspects relating to working with adults with bipolar disorder require modification to be effective in working with young people early in the course of the disorder.
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/BDI.12501
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.GENHOSPPSYCH.2014.01.009
Abstract: To examine the relationship of poor dental health and depression, controlling for markers of inflammation (C-reactive protein CRP) and adiposity (body mass index BMI). Data from two National Health and Nutrition Examination Surveys (2005-2008) were utilized (n=10214). Dental health was assessed using the Oral Health Questionnaire (OHQ). Depression was measured using the Patient Health Questionnaire-9 (PHQ-9), where cases were identified using a cut off score of 10 or above. Logistic regression was applied to measure magnitude of associations, controlling for a range of covariates including CRP and BMI. After adjustment for covariates, a significant dose-response relationship between number of oral health conditions and likelihood of PHQ-9 defined depression was observed. Compared with in iduals without an oral health condition, adjusted odds ratio (95% confidence interval) for depression in those with two, four and six conditions were 1.60 (1.08-2.38), 2.13 (1.46-3.11) and 3.94 (2.72-5.72), respectively. Level of CRP and being underweight or obese were associated with being depressed. A positive association exists between poor dental health and depression that is independent of CRP and BMI.
Publisher: Wiley
Date: 16-04-2013
DOI: 10.1111/ACPS.12122
Abstract: To be used in conjunction with 'Psychological management of unipolar depression' [L e et al. Acta Psychiatr Scand 2013 (Suppl. 443):24-37] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013 (Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009 (Suppl. 439):27-46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. The pharmacotherapy of depression is an iterative process that often results in partial and non-response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to prescribe because of the paucity of pertinent research. However, there is some evidence for second-line strategies, and a non-prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation-specific factors often play a significant role and must be considered, especially in the case of partial and non-response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2008
Publisher: JMIR Publications Inc.
Date: 31-03-2021
DOI: 10.2196/24871
Abstract: Online interventions can be a cost-effective and efficient way to deliver programs to large numbers of people regardless of geographic location. However, attrition in web-based interventions is often an issue. Developing ways to keep participants engaged is important for ensuring validity and limiting potential biases. We developed a web-based dietary intervention as part of The My Food & Mood study which aimed to optimize ways to engage participants with low mood or depressive symptoms to promote dietary behavior change. Different versions of the My Food & Mood program were tested during optimization. Iterations were developed based on user feedback and usage analysis. The purpose of this study was to compare engagement and nonusage attrition across 4 program iterations—which differed by platform format, delivery mode, and activity type—to create an optimized version. Each program version contained modular videos with key activities with respect to implementing behavior change techniques of equivalent levels of required participation and length: version 1.0, desktop program and smartphone app version 2.1, desktop or smartphone program version 2.2, desktop program and version 3.0, smartphone app. Adults with PHQ-8 scores of 5 or greater were recruited online and assigned to 1 of the 4 versions. Participants were asked to use the program for 8 weeks and complete measures at weeks 4 and 8. Engagement data were collected from the web-based platform system logs and customized reports. Cox regression survival analysis examined nonusage attrition and Kruskal-Wallis tests compared engagement across each cohort. A total of 614 adults participated. Kruskal-Wallis tests showed significant differences across the 4 cohorts in all engagement measures. The smartphone app (version 3.0) had the greatest engagement as measured by weeks engaged, total usage time, total time key activities, number of active sessions, percentage of activities completed against protocol, goals completed, and percentage of videos watched. Cox regression multivariate survival analysis showed referral from a health practitioner (hazard ratio [HR] 0.344, P=.001) and greater proficiency with computers (HR 0.796, P=.049) reduced the risk of nonusage attrition. Computer confidence was associated with an increased risk of nonusage attrition. My Food & Mood version 3.0, a dietary intervention delivered via smartphone app with self-monitoring tools for diet quality and mood monitoring, was the version with greatest engagement in a population with low mood or depression. The iterative design techniques employed and analysis of feedback from participants resulted in a program that achieved lower rates of nonusage attrition and higher rates of intensity of use.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JAD.2014.12.010
Abstract: Bipolar disorder (BD) is commonly comorbid with many medical disorders including atopy, and appears characterized by progressive social, neurobiological, and functional impairment associated with increasing number of episodes and illness duration. Early and late stages of BD may present different biological features and may therefore require different treatment strategies. Consequently, the aim of this study was to evaluate serum levels of eotaxin/CCL11, eotaxin-2/CCL24, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFNγ, BDNF, TBARS, carbonyl, and GPx in a s le of euthymic patients with BD at early and late stages compared to controls. Early-stage BD patients, 12 late-stage patients, and 25 controls matched for sex and age were selected. 10mL of peripheral blood was drawn from all subjects by venipuncture. Serum levels of BDNF, TBARS, carbonyl content, glutathione-peroxidase activity (GPx), cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFNγ), and chemokines (eotaxin/CCL11 and eotaxin-2/CCL24) were measured. There were no demographic differences between patients and controls. No significant differences were found for any of the biomarkers, except chemokine eotaxin/CCL11, whose serum levels were higher in late-stage patients with BD when compared to controls (p=0.022 Mann-Whitney U test). Small number of subjects and use of medication may have influenced in our results. The present study suggests a link between biomarkers of atopy and eosinophil function and bipolar disorder. These findings are also in line with progressive biological changes partially mediated by inflammatory imbalance, a process referred to as neuroprogression.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2020
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 02-2022
Publisher: EDITORA SCIENTIFIC
Date: 08-2021
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.JPSYCHORES.2012.03.001
Abstract: The objective of this study was to investigate the association between pain and mood and anxiety disorders, as well as psychological symptoms, in a population-based s le of women. This study examined the data collected from 1067 women aged 20-93years (median 51years) participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were diagnosed using a clinical interview (SCID-I/NP) and psychological symptomatology was assessed using the General Health Questionnaire. Pain was determined using a Visual Analogue Scale (0-100mm) and deemed present if score≥40mm. Current mood disorders were associated with an increased likelihood of overall (OR=3.2, 95% CI 2.0-5.1), headache (OR=2.8, 95% CI 1.6-4.8), back (OR=4.0, 95% CI 2.5-6.5) and shoulder pain (OR=2.2, 95% CI 1.2-4.2). In those with current mood disorders, the pain interfered with daily activities (OR=3.2, 95% CI 1.9-5.5) and was present most of their time awake (OR=2.5, 95% CI 1.5-4.1). This pattern was similarly observed for those with past mood disorders. Current anxiety disorders were associated with an increased likelihood for overall (OR=2.2, 95% CI 1.4-3.6), headache (OR=2.2, 95% CI 1.3-4.0), back (OR=1.8, 95% CI 1.1-3.0) and shoulder pain (OR=1.9, 95% CI 1.0-3.5, p=.05). In those with current anxiety disorders, the pain interfered with daily activities (OR=2.4, 95% CI 1.4-4.1) and was present most of their time awake (OR=1.9, 95% CI 1.2-3.2). There was no association between pain and past anxiety. Psychological symptomatology was associated with pain at each site (all p<.001). This study is consistent with studies utilising clinical s les in reporting that mood and anxiety disorders, as well as psychological symptoms, are associated with higher levels of perceived pain.
Publisher: Elsevier BV
Date: 2015
Publisher: Cambridge University Press (CUP)
Date: 11-07-2022
DOI: 10.1017/S1092852922000888
Abstract: Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.
Publisher: Wiley
Date: 27-07-2020
DOI: 10.1111/BDI.12974
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JAD.2013.10.008
Abstract: Medical illness is a risk factor for suicidality however, disorder-specific risks are not well-known and these relationships are often explained by major depressive disorder (MDD). We aimed to investigate the relationship between suicidal ideation, MDD and medical illnesses in an age-stratified, population-based s le of men participating in the Geelong Osteoporosis Study. Suicidal ideation and medical conditions were self-reported. Medical conditions were confirmed by medical records, medication use or clinical data where possible. MDD was determined using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition. Of the 907 men, 8.5% reported suicidal ideation. Thyroid disorders (OR 3.85, 95%CI 1.2-12.1), syncope and seizures (OR 1.96, 95%CI 1.1-3.5), liver disorders (OR 3.53, 95%CI 1.1-11.8 younger men only) and alcoholism (OR 2.15, 95%CI 1.1-4.4) were associated with increased odds of suicidal ideation, independent of age and MDD. Major vascular events doubled the odds of suicidal ideation but this was explained by MDD. No association was evident with high medical burden, musculoskeletal disease, metabolic factors, gastrointestinal disorders, headaches, cardiovascular disease, COPD, cancer and psoriasis. Health care professionals should focus on identification, assessment and management of suicidal ideation in the medically ill in patients both with and without MDD.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2021
DOI: 10.1007/S43465-020-00327-9
Abstract: Fractures through the physis account for 18–30% of paediatric fractures and can lead to growth arrest in 5–10% of these cases. Long-term radiographic follow-up is usually necessary to monitor for signs of growth arrest at the affected physis. Given plain radiographs of a physeal fracture obtained throughout patient follow-up, different surgeons may hold different opinions about whether or not early growth arrest has occurred despite using identical radiographs to guide decision-making. This study aims to assess the inter-rater and intra-rater reliability of early growth arrest diagnosis among orthopaedic surgeons given a set of identical plain radiographs. A retrospective chart review was conducted on patients aged 2–18 years previously treated for a physeal fracture at a paediatric tertiary care hospital between 2011 and 2018. De-identified anteroposterior (AP) and lateral radiographs of 39 patients from the date of injury and minimum one-year post-injury were administered in a survey to international paediatric orthopaedic surgeons. Each surgeon was asked whether they would diagnose the patient with growth arrest based on the radiographs provided. Surgeons were asked to complete this process again two weeks after the initial review, but using identical shuffled radiographs. Inter-rater and intra-rater reliability was calculated using appropriate kappa statistics. A total of 11 paediatric orthopaedic surgeons completed the first round of the survey, and 9 of these 11 completed the second round. The inter-rater reliability for the first round was 0.22 [95% CI (0.06, 0.35)] and 0.21 [95% CI (0.02, 0.32)] for the second round. The average kappa for intra-rater reliability was − 0.05 [95% CI (− 0.31, 0.21)]. Comparison by injury side showed no significant variation in diagnosis { p = 0.509, OR = 0.90, [95% CI (0.67, 1.22)]}, while comparison by location of injury varied significantly ( p = 0.003). Radiographic diagnosis of growth arrest among paediatric orthopaedic surgeons demonstrated ‘fair’ inter-rater agreement and no intra-rater agreement, suggesting critical differences in identifying growth arrest on plain radiographs. Further research is necessary to develop an improved diagnostic approach for growth arrest among orthopaedic surgeons. Diagnostic level III.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.JAD.2010.12.019
Abstract: There is increasing evidence suggesting oxidative stress may play a role in the aetiology of depression. Glutathione is the brain's predominant free radical scavenger, and associated polymorphisms of the glutamate cysteine ligase (GCL) gene have been reported for related psychiatric disorders. The aim of the study was to investigate candidate polymorphisms of GCL validated in schizophrenia and their association with current state depression, as measured by the Hospital Anxiety and Depression Scale (HADS). Polymorphisms were genotyped on 983 cases and 967 controls selected from a population s le of adults participating in the Nord-Trøndelag Health Study. Cases were the top scoring in iduals (98.5th percentile) on the HADS depression subscale while the controls were randomly selected from below this cut-off. The polymorphisms comprised three SNPs from GCLM, the gene encoding the GCL modifier and 9 SNPs plus a trinucleotide repeat (TNTR) from intron 1 and the 5'UTR of GCLC, the gene encoding the GCL catalytic subunit. Using the linkage disequilibrium between the GCLC markers we also tested whether SNPs could represent the variation of the TNTR. The candidate polymorphisms showed no evidence for association with depression. The C allele of SNP rs9474592 is coupled with the 9 GAG repeats allele of the TNTR, r²=0.81. None of the other SNPs either in idually or as two or three-SNP haplotypes was associated with the TNTR alleles. Depression was self-reported and measured at one time point. This study provides no evidence to suggest that polymorphisms of GCL are associated with self-reported depression.
Publisher: Informa UK Limited
Date: 10-2006
Abstract: Bipolar disorder has a major deleterious impact on many aspects of a patient's functioning and health-related quality of life. Although the formal measurement of these deficits has been neglected until recently, many well-designed trials now include an assessment of functioning and health-related quality of life using one or more rating scales. This review describes recent developments in the measurement of functioning and health-related quality of life in bipolar disorder, and discusses the evidence that medications that improve symptoms in bipolar disorder also offer clinically relevant benefits in functioning and health-related quality of life. Direct comparisons of the benefits of medications including atypical antipsychotics are problematic due to differences in trial populations, study durations and rating scales. Data from quetiapine trials indicate that this medication offers prompt and sustained improvement of functioning in patients with mania and enhancement of health-related quality of life in patients with bipolar depression, to accompany the significant improvements in mood episodes.
Publisher: Cambridge University Press (CUP)
Date: 08-2010
Publisher: EDITORA SCIENTIFIC
Date: 02-2020
Publisher: SAGE Publications
Date: 15-08-2014
Abstract: To determine the association between insomnia, obstructive sleep apnoea (OSA), and comorbid insomnia-OSA and depression, while controlling for relevant lifestyle and health factors, among a large population-based s le of US adults. We examined a s le of 11,329 adults (≥18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2005–2008. Insomnia was classified via a combination of self-reported positive physician diagnosis and high-frequency ‘trouble falling asleep’, ‘waking during the night’, ‘waking too early’, and ‘feeling unrested during the day’. OSA was classified as a combination of a positive response to a physician-diagnosed condition, in addition to a high frequency of self-reported nocturnal ‘snoring’, ‘snorting/stopping breathing’ and ‘feeling overly sleepy during the day’. Comorbid insomnia-OSA was further assessed by combining a positive response to either insomnia (all), or sleep apnoea (all), as classified above. Depressive symptomology was assessed by the Patient Health Questionnaire-9 (PHQ-9), with scores of used to indicate depression. Odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disorders and depression were attained from logistic regression modelling adjusted for sex, age, poverty level, smoking status and body mass index (BMI). Those who reported insomnia, OSA or comorbid insomnia-OSA symptoms reported higher rates of depression (33.6%, 22.2%, 27.1%, respectively), and consistently reported poorer physical health outcomes than those who did not report sleep disorders. After adjusting for sex, age, poverty level, smoking status and BMI (kg/m 2 ), insomnia (OR 6.57, 95% CI 3.89-11.11), OSA (OR 5.14, 95% CI 3.14–8.41) and comorbid insomnia-OSA (OR 6.67, 95% CI 4.44–10.00) were associated with an increased likelihood of reporting depression. Insomnia, OSA and comorbid insomnia-OSA are associated with significant depressive symptomology among this large population-based s le of adults.
Publisher: FapUNIFESP (SciELO)
Date: 2009
Publisher: FapUNIFESP (SciELO)
Date: 2009
Publisher: SAGE Publications
Date: 26-11-2013
Abstract: Concerns have emerged that initiation of an antidepressant can lead to or exacerbate suicidality. If those more at risk could be identified prior to treatment, treatment risk benefit analysis and patient risk management could be assisted. This study investigated the role of child abuse and ongoing emotional impact from abuse on the risk of suicidality during the first week of treatment with an antidepressant. The patient s le for this study was drawn from one site of a larger pharmacogenetic study. The hypothesis was that subjects with high impact child abuse would have greater elevation of suicidality during the first week of antidepressant treatment. Fifty-one subjects were initiated on either venlafaxine (VEN) or escitalopram (ESC) for major depressive disorder (MDD) and had pre-treatment suicidality assayed with the reasons for living scale (RFLS), which was repeated after one week of treatment. Several clinical, demographic and genotype variables were controlled for. The 15-item Impact of Event Scale (IES-15) was administered to subjects reporting abuse to dichotomise the abuse group into low and high (IES-15 ≥ 26) impact groups for sub-analysis as per the scales validated rating guidelines. Subjects reporting no child abuse exposure were less likely to have increased suicidality during the first week of antidepressant treatment (7.6%) compared to subjects with low impact abuse (38.5%, p = 0.041) and high impact abuse (58.3%, p = 0.009). Only high impact abuse predicted increased suicidality after adjustment for potential confounders such as depression severity (OR = 31.5, 95% CI = 1.3 to 748.7, p = 0.03). If these findings are replicated in larger s les, child abuse history could become an important element of assessing risk benefit balance when initiating antidepressants and may help guide the level of patient review needed during antidepressant initiation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 29-06-2023
DOI: 10.1038/S41380-023-02134-8
Abstract: Bipolar disorder’s core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression–mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine’s potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine’s demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JAD.2013.03.023
Abstract: The relationship between remission and quality of life in bipolar disorder is incompletely understood. This study aimed to determine cut-points on the 36-item Short-Form Health Survey (SF-36) and the European Quality of Life Index (EQ-5D) that corresponded with an objective clinical measure of remission in bipolar disorder patients. Data from a 2-year prospective observational study of bipolar and schizoaffective patients were analysed. Concordant with previous research, the Clinical Global Impression-Bipolar Version (CGI-BP) was used as an index of remission, specifically the severity scores of 1 (normal, not at all ill) and 2 (borderline mentally ill). The mean SF-36 standardized mental component (SMC) and standardized physical component (SPC) total scores as well as the EQ-5D index score that corresponded with a CGI-BP severity score of 1 or 2 were determined. The mean SF-36 score that corresponded with a CGI-BP severity score of 1 or 2, was below 50 for the SPC (49.3) and below 49 for the SMC (48.3). The mean EQ-5D score that corresponded with a CGI-BP severity score of 1 or 2 was below 0.88 (0.87). Although the initial s le is sufficiently large (n=240), 49 patients scored 1 and 2 on the CGI-S, of which 12 had schizoaffective disorder. This study suggests that a cut-off score of ≥50 for the SPC and ≥49 for the SMC of the SF-36 and ≥0.88 for the EQ-5D index approximates a CGI-BP definition of remission.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.EJPHAR.2010.09.035
Abstract: Glutathione (GSH) is the primary antioxidant in the body and is present in high levels in the brain. Levels of GSH and other antioxidants are significantly altered in major psychiatric illnesses, such as schizophrenia. Recent clinical trials have demonstrated that chronic treatment with N-acetyl-l-cysteine (NAC), a GSH precursor, improved symptoms in in iduals with this illness. We previously showed in rats and mice that depletion of GSH by treatment with 2-cyclohexene-1-one (CHX) induced short-term spatial memory deficits in the Y-maze test. The aim of present study was to characterise the effect of NAC in this CHX-induced glutathione depletion model. Consistent with our previous studies, CHX treatment induced approximately 50% reduction of GSH levels in striatum, hippoc us and frontal cortex tissue. GSH depletion was significantly rescued by either 1.2 g/kg or 1.6 g/kg of NAC administration, with a full recovery observed in the frontal cortex after the high dose of NAC. CHX treatment also induced a disruption in short-term spatial recognition memory in Y-maze test, as measured by the duration of time spent in the novel arm. This disruption was reversed by treatment with 1.6 g/kg of NAC. In conclusion, this study suggests that rescue of depleted levels of GSH in the brain restores cognitive deficits, as measured by the Y-maze. These effects appear to be dose-dependent and region-specific. These results may be relevant to the understanding and management of the cognitive symptoms of schizophrenia and bipolar disorder.
Publisher: SAGE Publications
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 31-07-2015
DOI: 10.1007/S11914-015-0279-7
Abstract: While it is understood that body composition impacts on physical conditions, such as diabetes and cardiovascular disease, it is only now apparent that body composition might play a role in the genesis of common mental disorders, depression and anxiety. Sarcopenia occurs in ageing and comprises a progressive decline in muscle mass, strength and function, leading to frailty, decreased independence and poorer quality of life. This review presents an emerging body of evidence to support the hypothesis that shared pathophysiological pathways for sarcopenia and the common mental disorders constitute links between skeletal muscle and brain function. Contracting skeletal muscle secretes neurotrophic factors that are known to play a role in mood and anxiety, and have the dual role of nourishing neuronal growth and differentiation, while protecting the size and number of motor units in skeletal muscle. Furthermore, skeletal muscle activity has important immune and redox effects that impact behaviour and reduce muscle catabolism.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.JAD.2010.08.001
Abstract: The evidence base for the pharmacological treatment of bipolar II disorder is limited. In bipolar disorder, there is evidence for glutathione depletion and increased oxidative stress, as well as dysregulation of glutamate N-acetyl cysteine (NAC) has effects on both of these systems. Add-on NAC has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. In this report, we explore the effects of this compound in a subset of patients with bipolar II disorder from that trial. In iduals were randomized to NAC or placebo in addition to treatment as usual, in a double-blind fashion. Mood and functional outcomes were assessed up to 24 weeks of treatment. Fourteen in iduals were available for this report, seven in each group. Six people achieved full remission of both depressive and manic symptoms in the NAC group this was true for only two people in the placebo group (χ(2)=4.67, p=0.031). Subgroup analyses in a small subs le of patients. Not all participants had elevated depression scores at baseline. Notwithstanding all the limitations that subgroup analysis of trials carry, this data could serve as a hypothesis-generating stimulus for further clinical trials of pharmacologic treatment for bipolar II depression.
Publisher: Cold Spring Harbor Laboratory
Date: 03-02-2023
DOI: 10.1101/2023.02.02.23285397
Abstract: Parkinson’s disease is a progressive neurodegenerative disorder characterised by motor dysfunction and cognitive disruption among other non-motor symptoms. No cure for Parkinson’s disease exists. Deep Brain Stimulation of the Subthalamic Nucleus (DBS STN) has been utilised for control of motor symptoms. However, cognitive deficits are commonly reported after implantation, and few exhaustive analyses exist to quantify and explain them. Our systematic review, meta-analyses, and metaregressions examine within-subjects change across thirteen cognitive domains, from 70 studies and 3000 participants at baseline measurements. Improvement was not observed in any domain, but substantial decline at 12 months was observed for phonemic and categorical fluency, which appeared to stabilise 24 to 36 months. Meta-regression suggests that few study characteristics are predictive of longitudinal outcomes, and we propose that further research into specific surgical or placement effects is necessary to mitigate short-term cognitive change after DBS STN in Parkinson’s disease.
Publisher: Oxford University Press (OUP)
Date: 04-2018
Publisher: Springer Science and Business Media LLC
Date: 13-02-2018
Publisher: MDPI AG
Date: 17-02-2023
DOI: 10.3390/JCM12041610
Abstract: This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Publisher: SAGE Publications
Date: 15-05-2013
Abstract: Excessive daytime sleepiness (EDS) is a common clinical symptom that affects women more than men. However, the association of excessive sleepiness with depressive and anxiety disorders in the broader population is unclear. The aim of this study was, therefore, to examine the association between excessive daytime sleepiness as measured by the Epworth Sleepiness Scale, and depressive and anxiety disorders in a population-based s le of women. Using the Structured Clinical Interview for DSM-IV Disorders (Non-Patient) (SCID-I/NP), 944 women aged 20–97 years (median 49 years, IQR 33–65 years) were assessed for depressive and anxiety disorders as part of the Geelong Osteoporosis Study. EDS was assessed using the Epworth Sleepiness Scale (ESS, cut-off 10). Lifestyle factors were documented by self-report, height and weight were measured, and socioeconomic status categorised according to the Index of Relative Socio-Economic Advantage and Disadvantage. Overall, 125 (13.2%) of the women were identified with EDS. EDS was associated with an increased likelihood for both current (OR = 2.11, 95% CI 1.10–4.06) and lifetime history (OR = 1.95, 95% CI 1.28–2.97) of depressive disorders, but not anxiety disorders, independent of age and alcohol consumption. These findings were not explained by antidepressant or sedative use, body mass index, physical activity, smoking, or socioeconomic status. These results suggest that excessive daytime sleepiness is associated with current and lifetime depressive, but not anxiety disorders. Clinically, this highlights the need to take into account the possible bidirectional relationship between depressive disorders and excessive sleepiness when assessing mental health issues in patients with EDS.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2020
Publisher: MDPI AG
Date: 10-09-2021
DOI: 10.3390/JCM10184095
Abstract: Weight gain and consequent metabolic alterations are common side-effects of many antipsychotic drugs. Interestingly, several studies have suggested that improvement in symptoms and adverse metabolic effects are correlated. We used next generation sequencing data from NT-2 (human neuronal) cells treated with aripiprazole, amisulpride, risperidone, quetiapine, clozapine, or vehicle control, and compared with the Pillinger P-score (ranked from 0 to 1, indicating greater increase in weight gain and related metabolic parameters) to identify the genes most associated with the drugs’ propensity to cause weight gain. The top 500 genes ranked for their correlation with the drugs’ propensity to cause weight gain were subjected to pathway analysis using DAVID (NIH). We further investigated transcription factors (TFs) that are more likely to regulate the genes involved in these processes using the prediction tool of key TFs from TRRUST. The results suggest an enrichment for genes involved in lipid biosynthesis and metabolism, which are of interest for mechanisms underpinning weight-gain. The list of genes involved in the lipid pathways that correlated with weight gain was enriched for genes transcriptionally regulated by SREBF1 and SREBF2. Furthermore, quetiapine significantly increased the expression of SREBF1 and SREBF2 in NT-2 cells. Our results suggest that the effects of these antipsychotic drugs on lipid metabolism may be mediated, at least in part, via regulation of SREBF1/SREBF2 expression, with evidence of a direct effect of quetiapine on the expression of SREBF1/2. The effects of antipsychotic drugs on lipid metabolism may influence white matter structure (therapeutic effect) and the risk of weight gain, lipid disturbances, and, consequently, metabolic syndrome (adverse effects). Understanding the different molecular effects of these drugs could inform a personalized medicine approach in treating patients with schizophrenia.
Publisher: Frontiers Media SA
Date: 15-06-2021
DOI: 10.3389/FPSYT.2021.626486
Abstract: Background: Cognitive impairment is prevalent and often highly burdensome in people with schizophrenia. The aim of this study was to investigate if mangosteen ( Garcinia mangostana Linn.) pericarp extract may be an effective intervention to improve cognitive performance in this population. Methods: This was a secondary analysis of a larger randomized placebo-controlled trial that investigated a 24-weeks intervention of mangosteen pericarp extract supplementation in people diagnosed with schizophrenia. A subset of n = 114 participants with completed cognitive outcomes at follow up were included in this analysis. Using the Cogstate Brief Battery, the following cognitive outcomes were assessed: psychomotor function, attention, visual learning and memory (visual and working). Subgroup analyses investigated whether baseline clinical parameters (baseline cognitive functioning, illness severity and duration, depressive symptoms) moderated the relationship between mangosteen pericarp extract intervention and change in cognitive outcomes. Results: There were no significant between-group changes in any cognitive outcomes assessed. Subgroup analysis based on baseline cognition and clinical characteristics did not reveal any significant between-group difference in change. Conclusions: Mangosteen pericarp extract did not affect cognitive outcomes in people with schizophrenia. Further investigation regarding optimal dosing strategies for mangosteen interventions and the testing of additional cognitive domains may be warranted. Trial Registration: ANZCTR.org.au identifier: ACTRN12616000859482, registered 30 June 3 2016.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.NEULET.2009.09.019
Abstract: Neuregulin (NRG) 1Ialpha and NRG3 proteins levels were measured in Brodmann's area 46 from 20 subjects with schizophrenia, 8 subjects with bipolar 1 disorder and 20 age-sex matched control subjects. Protein levels of both NRG1Ialpha and NRG3 were unchanged in both psychiatric illnesses. These data suggest any change in NRG1Ialpha and NRG3 expression in schizophrenia or bipolar 1 disorder do not result in changes levels in levels of those proteins Brodmann's area 46.
Publisher: Oxford University Press (OUP)
Date: 20-07-2022
Abstract: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of in iduals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC). A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11 Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26). NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with “Australian and New Zealand Clinical Trials” on the 30 May, 2016 (Registration Number: ACTRN12615001273572).
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
Publisher: American Psychiatric Association Publishing
Date: 06-2016
DOI: 10.1176/APPI.AJP.2016.15091228
Abstract: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted. A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies funnel plots also revealed asymmetry (reflecting potential study bias). Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.
Publisher: Physicians Postgraduate Press, Inc
Date: 27-05-2015
DOI: 10.4088/JCP.14L09378
Publisher: SAGE Publications
Date: 21-07-2019
Publisher: Informa Healthcare
Date: 06-11-2008
DOI: 10.1517/14728220802517901
Abstract: Glutathione is an endogenous antioxidant and has a ubiquitous role in many of the body's defences. Treatment with N-acetylcysteine (NAC) has been shown to increase levels of glutathione. NAC has been proposed as a treatment for several illnesses. The efficacy and tolerability of NAC was examined across a range of conditions to evaluate the evidence supporting the use of NAC for each indication. A literature search was conducted using PubMed. Information was also collected from other online sources including the websites of the Therapeutic Goods Administration of Australia and the FDA. Reports ranged from case studies to clinical trials. There is strong evidence to support the use of NAC for the treatment of paracetamol overdose and emerging evidence suggesting it has utility in psychiatric disorders, particularly schizophrenia and bipolar disorder. NAC is safe and well tolerated when administered orally but has documented risks with intravenous administration.
Publisher: SAGE Publications
Date: 14-05-2020
Publisher: Springer Science and Business Media LLC
Date: 21-02-2017
DOI: 10.1038/TP.2017.13
Abstract: Correction to: Translational Psychiatry (2017) 7, e1011 doi:10.1038/tp.2016.281 published online 24 January 2017 The 14th author’s name was presented incorrectly. The correct listing is C Pantelis.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.SCHRES.2013.02.036
Abstract: The diagnostic and clinical overlap between schizophrenia and schizoaffective disorder is an important nosological issue in psychiatry that is yet to be resolved. The aim of this study was to compare the clinical and functional characteristics of an epidemiological treated cohort of first episode patients with an 18-month discharge diagnosis of schizophrenia (FES) or schizoaffective disorder (FESA). This study was part of the larger First Episode Psychosis Outcome Study (FEPOS) which involved a medical file audit study of all 786 patients treated at the Early Psychosis Prevention and Intervention Centre between 1998 and 2000. Of this cohort, 283 patients had an 18-month discharge diagnosis of FES and 64 had a diagnosis of FESA. DSM-IV diagnoses and clinical and functional ratings were derived and validated by two consultant psychiatrists. Compared to FES patients, those with FESA were significantly more likely to have a later age of onset (p=.004), longer prodrome (p=.020), and a longer duration of untreated psychosis (p<.001). At service entry, FESA patients presented with a higher illness severity (p=.020), largely due to the presence of more severe manic symptoms (p<.001). FESA patients also had a greater number of subsequent inpatient admissions (p=.017), had more severe depressive symptoms (p=.011), and higher levels of functioning at discharge. The findings support the notion that these might be considered two discernable disorders however, further research is required to ascertain the ways and extent to which these disorders are discriminable at presentation and over time.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.NEULET.2014.08.020
Abstract: The measurement of the total radical trapping antioxidant potential (TRAP) is a general marker of peripheral blood antioxidant defenses. Paraoxonase 1 (PON1) is a potent antioxidant, which protects against lipid peroxidation. The study aimed to examine the relation between TRAP levels and PON1 activity, PON1 Q192R functional genotypes, smoking, interactions between PON1 genotypes and smoking, and mood disorders, while adjusting for effects of ethnicity, marital status, body mass index (BMI) and gender. The analyses were performed in 197 controls and 136 subjects with mood disorders. TRAP levels were significantly associated with higher plasma PON1 activity, the RR functional genotype, non smoking by RR carriers, male gender and a higher BMI. TRAP levels were significantly lower in patients with mood disorders than in controls, but this association was no longer significant after considering the effects of the above predictors. The risk in the subgroup with low TRAP levels is increased by a smoking X RR genotype interaction and decreased by male gender, the RR genotype, and higher BMI and PON1 activity. Plasma PON1 activity, the PON1 Q192R functional genotypes and specific interactions between this genotype and smoking contribute significantly to TRAP levels. Gender and BMI also appear to influence TRAP levels.
Publisher: Elsevier BV
Date: 05-2021
Publisher: BMJ
Date: 14-07-2017
Abstract: Randomised controlled trials (RCTs) are considered the ‘gold standard’ by which novel psychotropic medications and psychological interventions are evaluated and consequently adopted into widespread clinical practice. However, there are some limitations to using RCTs as the basis for developing treatment guidelines. While RCTs allow researchers to determine whether a given medication or intervention is effective in a specific patient s le, for practicing clinicians it is more important to know whether it will work for their particular patient in their particular setting. This information cannot be garnered from an RCT. These inherent limitations are exacerbated by biases in design, recruitment, s le populations and data analysis that are inevitable in real-world studies. While trial registration and CONSORT have been implemented to correct and improve these issues, it is worrying that many trials fail to achieve such standards and yet their findings are used to inform clinical decision making. This perspective piece questions the assumptions of RCTs and highlights the widespread distortion of findings that currently undermine the credibility of this powerful design. It is recommended that the clinical guidelines include advice as to what should be considered good and relevant evidence and that external bodies continue to monitor RCTs to ensure that the outcomes published indeed reflect reality.
Publisher: Springer Science and Business Media LLC
Date: 26-03-2022
DOI: 10.1007/S12035-022-02800-Y
Abstract: The endocannabinoid system (ECS) is composed of the endocannabinoid ligands anandamide (AEA) and 2-arachidonoylgycerol (2-AG), their target cannabinoid receptors (CB
Publisher: SAGE Publications
Date: 26-08-2014
Abstract: This study set out to test the relationship between attributions of responsibility for motor vehicle accidents and satisfaction with personal injury compensation systems. The study analysed survey data from 1394 people injured in a motor vehicle accident who were compensated under a no-fault personal injury compensation system. Patients’ ratings of satisfaction with the compensation system across five domains (resolves your issues, keeps you up-to-date, treats you as an in idual, cares about you, and overall satisfaction) were analysed alongside patient attributions of responsibility for their accident (not responsible, partly responsible, totally responsible). Postaccident physical and mental health status, age, gender, and duration of compensation claim were controlled for in the analysis. A multivariate analysis of covariance indicated attributions of responsibility for accidents were significantly associated with levels of patient satisfaction across all five domains under study ( F (10, 2084) = 3.7, p 0.001, η 2 = 0.02). Despite access to virtually indistinguishable services, patients who attributed responsibility for their accidents to others were significantly less satisfied with the injury compensation system than those who attributed responsibility to themselves. Satisfaction with no-fault motor vehicle injury compensation services are associated with patients’ attributions of responsibility for their accident. Compensation systems and other rehabilitation services monitoring patient satisfaction should adjust for attributions of responsibility when assessing levels of patient satisfaction between time periods, services, or injured populations. Differences in levels of patient satisfaction observed between compensation or rehabilitation populations may reflect differences in attributions of responsibility for accidents rather than objective service quality.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2022
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.JAD.2009.12.021
Abstract: Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative "high-risk" studies conducted in populations of bipolar off-spring such information may therefore be relevant only to a sub-group of at-risk subjects. Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses. Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are however likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our s le, may be an indicator of impending first episode mania. This is a retrospective study, in a small s le of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies. Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD could be a sign of impending first episode mania.
Publisher: Royal College of Psychiatrists
Date: 11-2012
DOI: 10.1192/BJP.BP.111.107797
Abstract: This editorial critiques the recent literature concerning both vitamin D deficiency in major depression and supplementation as a treatment strategy, and contextualises it within a broader approach to the prevention of depression, based on the recent evidence for lifestyle as a risk factor for depression and anxiety.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.PSYCHRES.2017.08.010
Abstract: We examined whether mental state disorders (lifetime mood, anxiety, eating, substance misuse) with comorbid personality disorder are associated with physical multimorbidity in a population-based s le of women. Mental state and personality disorders were assessed using semi-structured diagnostic interviews. Clinical measures were performed and medical conditions, medication use and lifestyle factors were documented by questionnaire. Mental state disorders were associated with higher odds of physical multimorbidity risk was especially high for those with comorbid personality disorder. These findings suggest that mental state and physical comorbidity might be worsened by the additional comorbidity of personality disorder.
Publisher: Massachusetts Medical Society
Date: 21-09-2017
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.PSYNEUEN.2010.01.014
Abstract: Estrogen treatment may enhance the recovery of schizophrenia in women. However, adverse effects on uterine and breast tissue and other physical side effects may limit the long-term therapeutic use of estrogen. Raloxifene hydrochloride is a selective estrogen receptor modulator that acts as an estrogen antagonist in breast tissue and may have agonistic actions in the brain, potentially offering mental health benefits with few estrogenic side effects. To provide an indication of the potential therapeutic dose for raloxifene hydrochloride in postmenopausal women with schizophrenia, this study pools data from an ongoing randomized controlled trial of adjunctive 120 mg/day oral raloxifene hydrochloride (n=13) versus oral placebo (n=13), with data from a previous pilot study administering 60 mg/day raloxifene hydrochloride (n=9). Analysis of variance found significant interaction effects for total (p=.01) and general (p=.02) Positive and Negative Syndrome Scale (PANSS) symptomatology. Participants randomized to receive 120 mg/day raloxifene hydrochloride experienced a significantly more rapid recovery of total and general psychotic symptoms compared to both 60 mg/day raloxifene hydrochloride and placebo. The demonstrated benefit of adjunctive treatment with 120 mg/day raloxifene hydrochloride offers support for the potential role of this selective estrogen receptor modulator in treating postmenopausal women with schizophrenia.
Publisher: Wiley
Date: 21-06-2019
DOI: 10.1111/BDI.12669
Abstract: MoodSwings 2.0 is an online self-guided intervention for bipolar disorder that includes educational modules, interactive tools, and discussion forums. The primary aim of the study was to determine if participation in MoodSwings 2.0 would result in decreased symptoms of depression and mania compared to the control condition. Secondary aims were to identify improvements in core depression symptoms, quality of life, medication adherence, functioning, and time to relapse. This was a three-arm randomized controlled trial that compared two intervention arms against a peer support control group (forum). A total of 304 adults aged 21 to 65 years with a diagnosis of bipolar disorder were assigned to a forum-only control group (Group 1 n = 102), a forum plus modules treatment group (Group 2 n = 102), or a forum, modules, and tools treatment group (Group 3 n = 100), in addition to usual care. There was a significant intervention impact showing improvement on the primary outcome of depression for Group 2 compared to Group 1 (P = .05) with effect sizes (Cohen's d) ranging from 0.17 to 0.43. There was also a significant intervention impact showing improvement on the secondary outcome of core depression for Group 2 (P = .02) and Group 3 (P = .05), but worse physical functioning for Group 3 (P = .01), compared to Group 1. This study provides evidence of the efficacy of internet-based psychoeducation interventions for bipolar disorder in reducing depressive symptoms. Further investigation is needed to assess effectiveness in a public program.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2015
DOI: 10.1007/S13246-015-0328-7
Abstract: A passive deep brain stimulation (DBS) device can be equipped with a rectenna, consisting of an antenna and a rectifier, to harvest energy from electromagnetic fields for its operation. This paper presents optimization of radio frequency rectifier circuits for wireless energy harvesting in a passive head-mountable DBS device. The aim is to achieve a compact size, high conversion efficiency, and high output voltage rectifier. Four different rectifiers based on the Delon doubler, Greinacher voltage tripler, Delon voltage quadrupler, and 2-stage charge pumped architectures are designed, simulated, fabricated, and evaluated. The design and simulation are conducted using Agilent Genesys at operating frequency of 915 MHz. A dielectric substrate of FR-4 with thickness of 1.6 mm, and surface mount devices (SMD) components are used to fabricate the designed rectifiers. The performance of the fabricated rectifiers is evaluated using a 915 MHz radio frequency (RF) energy source. The maximum measured conversion efficiency of the Delon doubler, Greinacher tripler, Delon quadrupler, and 2-stage charge pumped rectifiers are 78, 75, 73, and 76 % at -5 dBm input power and for load resistances of 5-15 kΩ. The conversion efficiency of the rectifiers decreases significantly with the increase in the input power level. The Delon doubler rectifier provides the highest efficiency at both -5 and 5 dBm input power levels, whereas the Delon quadrupler rectifier gives the lowest efficiency for the same inputs. By considering both efficiency and DC output voltage, the charge pump rectifier outperforms the other three rectifiers. Accordingly, the optimised 2-stage charge pumped rectifier is used together with an antenna to harvest energy in our DBS device.
Publisher: Cambridge University Press (CUP)
Date: 12-2009
DOI: 10.1111/J.1601-5215.2009.00430.X
Abstract: To provide a selected overview of the literature on psychosocial treatments for bipolar disorder Selective literature review Randomised controlled trials of psychosocial interventions in bipolar disorder fall largely into five categories, namely: psychoeducation, integrated treatments, family based therapy, cognitive behavioural therapy and interpersonal social rhythm therapy. Most studies have shown some benefit in terms of relapse prevention, but have tended to be effective for either the depressed or the manic pole, and not both. Broader outcome parameters such as quality of life have not been reported consistently. The mechanisms whereby treatments might exert their effects have not been clearly delineated. Many studies have excluded patients with bipolar II and other variants, and those with psychiatric and substance use comorbidities, reducing their generalisability. Whilst psychosocial treatments show promise in the area of bipolar disorder, more work is required to delineate the effective elements of such interventions, and to ensure generalisability to in iduals with bipolar II and other forms of bipolar disorder, as well as those with psychiatric and substance use comorbidities. Other forms of delivery, such as via the internet, deserve further exploration.
Publisher: American Medical Association (AMA)
Date: 28-12-2021
Publisher: Informa UK Limited
Date: 2012
DOI: 10.1586/ERN.11.174
Publisher: Springer Science and Business Media LLC
Date: 08-02-2017
Publisher: Springer Science and Business Media LLC
Date: 29-03-2013
DOI: 10.1007/S40520-013-0026-9
Abstract: Alcohol is calorie dense, and impacts activity, appetite and lipid processing. The aim of this study was to therefore investigate the association between alcohol consumption and components of body composition including bone, fat and lean tissue. Participants were recruited from a randomly selected, population-based s le of 534 men aged 65 years and older enrolled in the Geelong Osteoporosis Study. Alcohol intake was ascertained using a food frequency questionnaire and the s le categorised as non-drinkers or alcohol users who consumed ≤2, 3-4 or ≥5 standard drinks on a usual drinking day. Bone mineral density (BMD), lean body mass and body fat mass were measured using dual energy X-ray absorptiometry overall adiposity (%body fat), central adiposity (%truncal fat) and body mass index (BMI) were calculated. Bone quality was determined by quantitative heel ultrasound (QUS). There were 90 current non-drinkers (16.9 %), 266 (49.8 %) consumed 1-2 drinks/day, 104 (19.5 %) 3-4 drinks/day and 74 (13.8 %) ≥5 drinks/day. Those consuming ≥5 drinks/day had greater BMI (+4.8 %), fat mass index (+20.1 %), waist circumference (+5.0 %), %body fat (+15.2 %) and proportion of trunk fat (+5.3 %) and lower lean mass (-5.0 %) than non-drinkers after adjustment for demographic and lifestyle factors. Furthermore, they were more likely to be obese than non-drinkers according to criteria based on BMI (OR = 2.83, 95 %CI 1.10-7.29) or waist circumference (OR = 3.36, 95 %CI 1.32-8.54). There was an inverse relationship between alcohol consumption and QUS parameters and BMD at the mid forearm site no differences were detected for BMD at other skeletal sites. Higher alcohol intake was associated with greater total and central adiposity and reduced bone quality.
Publisher: Wiley
Date: 21-06-2018
DOI: 10.1111/BDI.12662
Abstract: In the clinical setting, the nocebo phenomenon is where clinical worsening or adverse events occur as a response to a treatment, in a situation in which conditioning from previous treatment exposure and/or expectations of sickness or symptoms lead to sickness and symptoms in a conditioned or expectant in idual. The nocebo response may thus be a confounder in clinical treatment and clinical research. There is a need to know how to predict if an in idual is likely to be a nocebo responder, and how significant and commonplace the nocebo effect might be. An analysis was conducted on nine placebo-controlled, randomized clinical trials of olanzapine for the treatment of bipolar disorder using data from placebo-treated study participants only. Data were analysed to identify participant or study characteristics associated with a nocebo event, defined as any treatment-emergent adverse event (TEAE) or an increase in score from baseline to endpoint for primary measures of clinical symptoms. A total of 1185 participants were randomized to placebo, of whom 806 (68%) reported a TEAE. Hamilton Depression Rating Scale (HDRS) data were only available for 649 placebo-treated participants, of whom 321 (49.5%) demonstrated worsening. Nocebo events were significantly associated with: not being treatment-naïve, younger age, being located in the USA, being a participant in an earlier study, and being classified as obese compared with normal weight. A pattern to identify nocebo responders did not emerge, although some prognostic variables were associated with a greater probability of nocebo response. There was some evidence to support the role of expectancy as a cause of nocebo reactions.
Publisher: Cambridge University Press (CUP)
Date: 09-08-2021
DOI: 10.1017/S1092852921000742
Abstract: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. There was a 3-year later age at onset for females ( P .001) and lower rates of negative symptoms ( P .01) and higher depression/anxiety measures ( P .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages ( P = .001). No significant effects were found concerning duration of illness. Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative s les.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 18-03-2013
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.SCHRES.2011.08.018
Abstract: Depressive symptoms in 'non-affective' first episode schizophrenia spectrum disorders (FES) are common, but poorly understood, resulting in a range of conceptual and clinical management issues. This study had three aims: (i) to determine the prevalence of moderate to severe depressive symptoms (defined as a Clinical Global Impressions Scale-Bipolar Disorder (CGI-BP depression) score >3) in a large representative s le of FES patients (ii) to compare the clinical and functional characteristics of FES patients with and without these depressive symptoms at service entry and (iii) to compare the characteristics of FES patients with and without persistent depressive symptoms. Medical file audit methodology was employed to collect information on 405 patients with FES treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. 26.2% (n=106) of the patients had moderate to severe depression at service entry. At service entry and at discharge, those with depressive symptoms had greater insight into their illness but did not differ from those without depressive symptoms in terms of severity of overall psychopathology. Substance use was significantly less common in those with depressive symptoms at service entry and at discharge. Of those who were depressed at baseline, 14.2% (n=15) continued to have moderate to severe depressive symptoms at discharge. Depressive symptoms are common in patients with FES. Understanding the nature and characteristics of depression in FES has important clinical implications for both early intervention and treatment.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JAD.2014.05.014
Abstract: Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-in idual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes. GBM was applied to pooled data from 12 randomised clinical trials of 4987 participants experiencing an acute depressive episode who were treated with duloxetine, an SSRI or placebo to predict treatment remission. Additional analyses were conducted on the same dataset using the logistic regression model for comparison between these two methods. With GBM, there were noticeable differences between treatments when identifying which and to what extent variables were associated with remission. A single logistic regression only revealed a decreasing or increasing relationship between predictors and remission while GBM was able to reveal a complex relationship between predictors and remission. These analyses were conducted post-hoc utilising clinical trials databases. The criteria for constructing the analyses data were based on the characteristics of the clinical trials. GBM can be used to identify and quantify patient variables that predict remission with specific treatments and has greater flexibility than the logistic regression model. GBM may provide new insights into inter-in idual differences in treatment response that may be useful for selecting in idualised treatments. IMPACT clinical trial number 3327 IMPACT clinical trial number 4091 IMPACT clinical trial number 4689 IMPACT clinical trial number 4298 NCT00071695 NCT00062673 NCT00036335 NCT00067912 NCT00073411 NCT00489775 NCT00536471 NCT00666757 (note that trials with IMPACT numbers predate mandatory clinical trial registration requirements).
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.JAD.2014.05.017
Abstract: This study investigated the impact of comorbid obsessive-compulsive disorder (OCD) and four anxiety disorders [panic disorder (PD), agoraphobia, social anxiety disorder (SAD), and generalized anxiety disorder (GAD)] on the clinical outcomes of bipolar disorder. This study analysed data of 174 patients with bipolar I disorder who participated in the prospective observational study. Participants were assessed every 3 months for 24 months. The primary outcome measure was the achievement of symptomatic remission, defined by a total score on the Young Mania Rating Scale (YMRS) of ≤12 and a total score on the 21-item Hamilton Depression Rating Scale (HAMD-21) of ≤8. Comorbidity was associated with decreased likelihood of remission. However, the impact of in idual disorders on outcome differed according to clinical and treatment situations. Most comorbid anxiety disorders and OCD had a negative effect on remission during the first year of evaluation, as measured by the HAMD-21, and in patients taking a conventional mood stabilizer alone. However, the association with poorer outcome was observed only for a few specific comorbid disorders in the second year (GAD and OCD), as measured by YMRS-defined remission (OCD), and in patients with olanzapine therapy (GAD and OCD). Follow-up evaluation of comorbid disorders was lacking. Comorbid anxiety disorders and OCD negatively influenced the clinical course of bipolar disorder. Specifically, OCD had a consistently negative impact on the outcome of bipolar I disorder regardless of clinical situation. Effective strategies for the control of these comorbidities are required to achieve better treatment outcomes.
Publisher: Royal College of Psychiatrists
Date: 17-04-2023
DOI: 10.1192/BJO.2023.36
Abstract: There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders. MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367. The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis diet duration: 2 weeks to 3 years n = 389 age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some in iduals. Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Springer Science and Business Media LLC
Date: 29-03-2023
DOI: 10.1038/S41398-023-02396-4
Abstract: Staging models with transdiagnostic validity across mood, psychotic, and anxiety disorders could advance early intervention efforts as well as our understanding of the common underpinnings of such psychopathology. However, there are few well-supported operationalisations for such transdiagnostic models, particularly in community-based s les. We aimed to explore the inter-relationships among mood, psychotic, and anxiety symptom stages, and their common risk factors to develop data-informed transdiagnostic stages. We included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective ongoing birth cohort study. We developed operational thresholds for stages of depressive, hypomanic, anxiety, and psychotic symptoms based on the existing literature, refined further by expert consensus. We selected 1b level as the primary stage or outcome of interest. This represents moderate symptoms that are likely to be associated with the onset of the need for clinical mental health care. We used questionnaire and clinic data completed by young people ages 18 and 21 years. We used descriptive methods and network analyses to examine the overlap among Stage 1b psychopathology. We then examined the patterns of relationships between several risk factors and 1b stages using logistic regressions. Among 3269 young people with data available to determine all symptom stages, 64.3% were female and 96% Caucasian. Descriptive and network analyses indicated that 1b level depressive, anxiety, and psychotic symptom stages were inter-related while hypomania was not. Similarly, anxiety, depressive, and psychotic 1b stages were associated with the female sex, more emotional and behavioral difficulties in early adolescence, and life events in late adolescence. Hypomania was not related to any of these risk factors. Given their inter-relationships and similar risk factors, anxiety, psychotic and depressive, symptoms could be combined to form a transdiagnostic stage in this cohort. Such empirical transdiagnostic stages could help with prognostication and indicated prevention in youth mental health.
Publisher: Informa UK Limited
Date: 11-11-2018
Publisher: MDPI AG
Date: 09-03-2023
DOI: 10.3390/IJMS24065250
Abstract: Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient opulation, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer’s disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.GENHOSPPSYCH.2007.06.005
Abstract: Depression is common but frequently undetected in patients with coronary artery disease (CAD). Self-report screening instruments for assessing depression such as the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9 (PHQ-9) are available but their validity is typically determined in depressed patients without comorbid somatic illness. We investigated the validity of these instruments relative to a referent diagnostic standard in recently hospitalized patients with CAD. Three months post-discharge for a cardiac admission, 193 CAD patients completed the HADS and PHQ-9. The Mini International Neuropsychiatric Interview (MINI) was the criterion standard. Scale reliability was calculated using Cronbach's alpha. Convergent validity was computed using Pearson's intercorrelations. Sensitivity and specificity for various cut-off scores for both measures and for the PHQ-9 categorical algorithm were calculated using receiver operating characteristics (ROC). For analyses, participants were assigned to two groups, 'major depressive disorder' or 'any depressive disorder'. For all calculations, alpha was 0.05 and tests were two-tailed. Internal consistencies for the two measures were excellent. Criterion validity for the PHQ-9 and HADS was good. We found no statistical differences between the PHQ-9 and HADS for detecting either group however, the categorical algorithm of the PHQ-9 for diagnosing major depression had a superior LR+ when compared with the summed HADS or PHQ-9. The operating characteristics of the screening instruments for 'any depressive disorder' were slightly lower than for 'major depressive disorder'. Some optimum cut-off scores were lower than the generally recommended cut-off scores, particularly when screening for major depression (e.g., > or = 5/6 vs. > or = 10 and > or = 8 for PHQ-9 and HADS, respectively). Lowering the cut off scores substantially improved the sensitivity of these instruments while retaining specificity, thereby improving their usefulness to screen for CAD patients with depression. Both instruments have acceptable properties for detecting depression in recently hospitalized cardiac patients, and neither scale is statistically superior when summed scores are used. The categorical algorithm of the PHQ-9 for diagnosing major depression has a superior LR+ compared to the summed PHQ-9 and HADS scores. Use of the generally recommended cut-off scores should be cautious. In light of the aversive outcomes associated with depression in CAD, screening for depression is a clinical priority.
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJOPEN-2020-041859
Abstract: In iduals with schizophrenia are known to be at higher risk of comorbid conditions, both physical and psychological. Osteoporosis is possibly one of these, leading to public health concerns due to higher rates of associated mortality and morbidity. We aim to systematically search all available evidence across electronic databases regarding the relationship between schizophrenia and bone fragility. A systematic search of the research databases CINAHL, MEDLINE Complete, Embase and PsycINFO will be conducted and identified papers reviewed for eligibility, with a second reviewer confirming inclusions. Searches will be run from database inception to 1 October 2020 and supplemented by the hand checking of references of identified articles. A previously published scoring system will be used for assessing the methodological quality and risk of bias. A meta-analysis is planned. Due to including published literature only, ethical permission will not be necessary. Results of this study will be published in a relevant scientific journal and presented at a conference in the field of interest. CRD42020171959.
Publisher: Wiley
Date: 09-09-2019
DOI: 10.1002/WPS.20672
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAD.2018.11.092
Abstract: One of the most pressing questions in "Nutritional Psychiatry" is whether using combinations of different nutraceuticals with putative antidepressant activity may provide an enhanced synergistic antidepressant effect. A phase II/III, Australian multi-site, 8-week, double-blind, RCT involving 158 outpatients with a DSM-5 diagnosis of MDD. The intervention consisted of a nutraceutical combination: S-adenosyl methionine Folinic acid Omega-3 fatty acids 5-HTP, Zinc picolinate, and relevant co-factors versus placebo. The primary outcome was change in MADRS score. Hypothesis-driven analyses of potential moderators of response involving key SNPs, and BDNF were also conducted. Placebo was superior to the nutraceutical combination in reducing MADRS score (differential reduction -1.75 points), however a mixed linear model revealed a non-significant Group X Time interaction (p = 0.33). Response rates were 40% for the active intervention and 51% for the placebo remission rates were 34% and 43% for active and placebo groups, respectively. No significant differences were found between groups on any other secondary depression, anxiety, psychosocial, or sleep outcome measures. Key SNPs and BDNF did not significantly moderate response. No significant differences occurred between groups for total adverse effects, aside from more nausea in the active group. Very high placebo response rates suggest a placebo run-in design may have been valuable. The adoption of a nutraceutical 'shotgun' approach to treating MDD was not supported, and appeared to be less effective than adding placebo to treatment as usual.
Publisher: Wiley
Date: 07-09-2018
DOI: 10.1002/WPS.20571
Publisher: SAGE Publications
Date: 29-03-2017
Abstract: Self-harm (defined here as an act of intentionally causing harm to own self, irrespective of the type, motive or suicidal intent) is one of the strongest antecedents of suicide in youth. While there have been a number of studies of youth self-harm in low- and middle-income countries (LMICs), there is currently no systematic review of studies of prevalence rates and risk and protective factors. To systematically review the evidence relating to the prevalence rates and forms of self-harm in youth in LMICs and its relationship to family economic status, family functioning, relationship with the peer group, social relationships and academic performance. Electronic searches of three databases, MEDLINE, PsycINFO and Scopus, were performed. In total, 27 school-, community- and hospital-based studies evaluating self-harm in LMICs with youth focus (with participants between 12 and 25 years) were included. The self-harm was ided into suicidal and non-suicidal depending on the nature of self-harm. The 12-month prevalence rates of non-suicidal self-harm varied from 15.5% to 31.3%, and the range of suicidal behaviour rates was from 3.2% to 4.7%. Banging and hitting were the most common in the community-based studies, followed by cutting, scratching and wound picking. Self-poisoning with pesticides was most commonly reported in hospital-based studies. Risk factors for self-harm were family conflict, peer groups with members indulging in self-harm, truancy and school absenteeism. Protective factors were having an understanding family, having friends and higher school competence. Risk factors for suicidal thoughts and attempts were lack of close friends and history of suicide by a friend. The 12-month prevalence rates of youth self-harm in LMICs are comparable to high-income countries (HICs). The profile of risk and protective factors suggests that family-based interventions could be useful in treatment and prevention. Future studies should aim for greater consistency in assessment methods and the constructs under evaluation.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.SCHRES.2010.02.1071
Abstract: In recent years, early intervention services have attempted to identify people with a first episode of psychosis as early as possible, reducing the duration of untreated psychosis and changing the timing of delivery of interventions. The logic of early intervention is based partly on accessing people in a more treatment responsive stage of illness in which psychosocial damage is less extensive, and partly on remediating a putatively active process of neuroprogression that leads to pathophysiological, symptomatic and structural changes, hence improving symptomatic and functional outcomes. However, as in other areas of health care, earlier identification of new patients may mean that different treatment approaches are indicated. The corollary of early detection is that the sequence and complexion of treatment strategies for first episode psychosis has been revaluated. Ex les include the minimal effective dosage of antipsychotic medication and the content of psychosocial interventions. With the substantial reductions of DUP now seen in many early psychosis services, based on clinical staging and stepped care principles, it is even possible that the immediate introduction of antipsychotic medication may not be necessary for all first episode psychosis cases, but that potentially safer interventions, which may be more acceptable to many patients, such as comprehensive psychosocial intervention, may constitute effective treatment at least for a subgroup of patients. In this paper, we review this theoretical background and describe a randomised controlled trial currently underway at the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne designed to test outcomes for first episode psychosis patients in response to two different treatments: intensive psychosocial intervention plus antipsychotic medication versus intensive psychosocial intervention plus placebo. This is a theoretically and pragmatically novel study in that it will provide evidence as to whether intensive psychosocial intervention alone is sufficient for a subgroup of first episode psychosis patients in a specialised early intervention service, and provide a test of the heuristic clinical staging model. By experimentally manipulating duration of untreated psychosis, the study will also provide a methodologically strong test of the effect of delaying the introduction of antipsychotic medication, as well as helping to disentangle the effects of antipsychotic medications and the putative neurobiological processes associated with brain changes and symptom profiles in the early phase of psychotic disorders. The study has been carefully crafted to satisfy critical ethical demands in this challenging research domain.
Publisher: SAGE Publications
Date: 18-02-2021
Abstract: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed “phytoceuticals,” in a similar way that medicinal nutrients are termed as “nutraceuticals.” Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a “meta-review” of this top-tier evidence. We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of in idual phytoceuticals across all major psychiatric disorders. Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 in iduals. Supportive meta-analytic evidence was found for St John’s wort for major depressive disorder (MDD) curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas’ meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias. More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.
Publisher: Wiley
Date: 09-11-2020
DOI: 10.1111/OBR.13146
Publisher: Springer Science and Business Media LLC
Date: 06-09-2019
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Wiley
Date: 05-11-2015
DOI: 10.1111/EIP.12280
Abstract: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether in iduals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with in iduals receiving placebo. YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2017
Publisher: Cambridge University Press (CUP)
Date: 31-05-2016
DOI: 10.1017/S104161021600079X
Abstract: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a s le size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. This paper presents the rationale for the study and presents a summary of the study design. ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
Publisher: BMJ
Date: 02-2020
DOI: 10.1136/BMJOPEN-2019-032821
Abstract: Little is known about the bone health of adults with bipolar disorder, aside from evidence purporting bone deficits among in iduals with other mental illnesses, or those taking medications commonly used in bipolar disorder. In this paper, we present the methodology of a case–control study which aims to examine the role of bipolar disorder as a risk factor for bone fragility. Men and women with bipolar disorder (~200 cases) will be recruited and compared with participants with no history of bipolar disorder (~1500 controls) from the Geelong Osteoporosis Study. Both cases and controls will be drawn from the Barwon Statistical Division, south-eastern Australia. The Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition is the primary diagnostic instrument, and psychiatric symptomatology will be assessed using validated rating scales. Demographic information and detailed lifestyle data and medical history will be collected via comprehensive questionnaires. Participants will undergo dual energy X-ray absorptiometry scans and other clinical measures to determine bone and body composition. Blood s les will be provided after an overnight fast and stored for batch analysis. Ethics approval has been granted from Barwon Health Research Ethics Committee. Participation in the study is voluntary. The study findings will be disseminated via peer-reviewed publications, conference presentations and reports to the funding body.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.JPSYCHIRES.2019.03.001
Abstract: In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p < 0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
Publisher: Wiley
Date: 13-08-2014
DOI: 10.1111/EIP.12166
Abstract: US authorities have recommended 'black-box' warnings for antidepressants because of the increased risk of suicidality for in iduals up to age 25. There is thus a clinical and ethical imperative to provide effective treatment for youth depression with an acceptable risk-benefit balance. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) play an important role in a range of physiological processes in living organisms. Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health, and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small s le sizes. This trial will test the effectiveness of a 12-week parallel group, double-blind, randomized, placebo-controlled trial of 1.4 g day(-1) omega-3 PUFAs in help seeking 15- to 25-year-olds (N = 400) presenting with major depressive disorder. The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management. Because of using a large s le, results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder. The study also heralds an important step towards indicated prevention of persistent depression, which may reduce the burden, stigmatization, disability and economic consequences of this disorder.
Publisher: Public Library of Science (PLoS)
Date: 21-02-2019
Publisher: Informa UK Limited
Date: 18-07-2014
Publisher: Wiley
Date: 29-01-2018
DOI: 10.1002/PHAR.2073
Abstract: Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability however, it is also considered the most preventable cause of death in developed countries. Since the development of nicotine replacement therapy (NRT) in 1978, treatment options have continued to evolve and expand. Despite this, currently available treatments remain insufficient, with less than 25% of smokers remaining abstinent 1 year after treatment. In this article, we review existing and emerging smoking cessation pharmacotherapies, with a special emphasis on the most promising agents that are currently being investigated. A search of the Cochrane Database of Systematic Reviews and the PubMed, Ovid, and ClinicalTrials.gov databases (August 2 to September 1, 2017) was undertaken for articles on smoking cessation pharmacotherapies, applying no language restrictions. More than 40 pharmacotherapies were reviewed including conventional pharmacotherapies-NRT, bupropion, and varenicline (all approved by the U.S. Food and Drug Administration as first-line treatment of smoking cessation)-and novel therapies: cytisine, N-acetylcysteine, cycloserine, memantine, baclofen, topiramate, galantamine, and bromocriptine. Studies of combination NRT and varenicline showed the greatest smoking cessation rates. Clonidine and nortriptyline are second-line treatments used when first-line treatments fail or are contraindicated, or by patient preference. Some novel therapies, especially acetylcholinesterase inhibitors, cytisine, and N-acetylcysteine, display promising results. Because the results of randomized clinical trials were reported using varied end points and outcome measures, direct comparisons between different pharmacotherapies cannot easily be evaluated. Additional high-quality randomized double-blind placebo-controlled trials with long-term follow-up, using validated sustained abstinence measures, are needed to find more effective smoking cessation aids.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.MATURITAS.2018.02.006
Abstract: Pretirees are a demographic interposed between the latter stages of working life and old age. We aimed to characterise subjective wellbeing and lifestyle behaviours for in iduals aged in their late-fifties and sixties. Cross-sectional study of 233 men and 229 women aged 55-69 yr from the Geelong Osteoporosis Study. Subjective wellbeing assessed using the World Health Organization Quality of Life questionnaire (WHOQOL-BREF, Australia). Scores below published population norms for Australia for WHOQOL domains (physical, psychological, social, environmental) were considered low. For men, low WHOQOL scores were evident for 78 (33.5%) of participants regarding physical health, 94 (40.3%) for psychological wellbeing, 89 (38.2%) for social relationships, and 99 (42.5%) for the environment the respective figures for women were 110 (48.0%), 124 (54.1%), 84 (36.7%), and 95 (41.5%). While there were few smokers (men 10.8% women 6.5%), 42.5% of men and 17.7% of women exceeded recommended alcohol levels 6.4% of men and 15.2% of women met the recommendation to consume each day at least two portions of fruit and five of vegetables. In multivariable models, being active was consistently associated with high WHOQOL scores, and low socioeconomic status with low WHOQOL scores. Pain and polypharmacy were associated with increased likelihood of poor scores for physical health, living with a partner increased the likelihood of good social relationships, and body mass index, employment, sleep, and alcohol and fruit/vegetable intakes were associated with WHOQOL scores in at least one domain. There is an opportunity for targeting health promotion to pretirees, particularly in socially disadvantaged regions, in order to optimise transition into old age. Our data highlight lifestyle interventions without which many pretirees might progress to old age at increased risk of diminished wellbeing.
Publisher: Wiley
Date: 21-09-2017
DOI: 10.1002/WPS.20441
Publisher: Cambridge University Press (CUP)
Date: 08-2008
Publisher: Elsevier BV
Date: 03-2022
Publisher: Frontiers Media SA
Date: 04-03-2015
Publisher: American Medical Association (AMA)
Date: 10-2016
Publisher: SAGE Publications
Date: 19-07-2016
Abstract: Cognitive deficits are apparent in the early stages of bipolar disorder however, the timing and trajectory of cognitive functioning following a first episode of mania remains unclear. The aim of this study was to assess the trajectory of cognitive functioning in people following a first episode of mania over a 12-month period, relative to healthy controls. The cohort included 61 participants who had recently stabilised from a first treated manic episode, and 21 demographically similar healthy controls. These groups were compared on changes observed over time using an extensive cognitive battery, over a 12-month follow-up period. A significant group by time interaction was observed in one measure of processing speed (Trail Making Test – part A,) and immediate verbal memory (Rey Auditory Verbal Learning Test – trial 1), with an improved performance in people following a first episode of mania relative to healthy controls. On the contrary, there was a significant group by time interaction observed on another processing speed task pertaining to focussed reaction time (Go/No-Go, missed go responses), with first episode of mania participants performing significantly slower in comparison with healthy controls. Furthermore, a significant group by time interaction was observed in inhibitory effortful control (Stroop effect), in which healthy controls showed an improvement over time relative to first episode of mania participants. There were no other significant interactions of group by time related to other measures of cognition over the 12-month period. Our findings revealed cognitive change in processing speed, immediate memory and one measure of executive functioning over a 12-month period in first episode of mania participants relative to healthy controls. There was no evidence of change over time for all other cognitive domains. Further studies focussed on the at-risk period, subgroup analysis, and the effects of medication on the cognitive trajectory following first episode of mania are needed.
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/BDI.12528
Publisher: Wiley
Date: 08-2011
DOI: 10.1111/J.1399-5618.2011.00942.X
Abstract: Berk L, Jorm AF, Kelly CM, Dodd S, Berk M. Development of guidelines for caregivers of people with bipolar disorder: a Delphi expert consensus study. Bipolar Disord 2011: 13: 556–570. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Close family and friends are often a primary source of support for a person with bipolar disorder. However, there is a lack of information for caregivers about ways to provide helpful support and take care of themselves. Rates of caregiver burden are high and increase the risk of caregiver depression and health problems. This study aimed to develop guidelines to assist caregivers of adults with bipolar disorder to be informed about bipolar disorder and to support the person without neglecting their own wellbeing. Methods: The Delphi method was used to assess consensus between international expert panels of 45 caregivers, 47 consumers, and 51 clinicians about what information to include in the caregiver guidelines. Initial online survey items were based on the existing literature. Subsequent surveys included new or reworded items suggested by panel members and items that needed re‐rating. Items endorsed by at least 80% of all three panels formed the content of the guidelines. Results: Nearly 86% of the 626 survey items were endorsed. The items covered information on the illness, treatment, and suggestions on ways caregivers can provide support and take care of themselves in the different phases of illness and wellness, and information on dealing with specific real‐life challenges. Although consensus rates were high, meaningful areas of difference between panels were found (e.g., collaboration issues). Conclusions: The guidelines provide comprehensive introductory information, suggestions, and resources for caregivers. Access to relevant information may help caregivers to cope constructively with the person’s bipolar disorder and their caregiving situation. The content of the guidelines could be used to help formulate a stepped‐care approach to supporting caregivers, ranging from basic information and p hlets to brief training courses and specialized family or caregiver interventions based on need and accessibility.
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.JAD.2012.02.018
Abstract: There is an increasing recognition of the role of nutrition in depression and anxiety. Magnesium, folate and zinc have all been implicated in depressive illness, however there are few data on these nutrients in anxiety disorders and the data from population-studies are limited. In a large, randomly-selected, population-based s le of women, this study aimed to examine the relationship between the dietary intakes of these three micronutrients and clinically determined depressive and anxiety disorders and symptoms. Nutrient intakes were determined using a validated food frequency questionnaire. The General Health Questionnaire-12 measured psychological symptoms, and a clinical interview (Structured Clinical Interview for DSM-IV-TR, non-patient edition) assessed current depressive and anxiety disorders. After adjustments for energy intake, each standard deviation increase in the intake of zinc, magnesium and folate was associated with reduced odds ratio (OR) for major depression/dysthymia (zinc: OR=0.52, 95% confidence interval (CI) 0.31 to 0.88 magnesium: OR=0.60, 95% CI 0.37 to 0.96 folate: OR=0.66, 95% CI 0.45 to 0.97). There was also an inverse association between the intake of magnesium and zinc and GHQ-12 scores (zinc: zβ=-0.16, 95% CI -0.29 to -0.04 magnesium: -0.14, 95% CI -0.26 to -0.03). These relationships were not confounded by age, socioeconomic status, education or other health behaviours. There was no relationship observed between any nutrient and anxiety disorders. These results demonstrate an association between the dietary intakes of magnesium, folate and zinc and depressive illnesses, although reverse causality and/or confounding cannot be ruled out as explanations.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.NEUBIOREV.2013.02.003
Abstract: Regular physical activity exerts positive effects on anxiety disorder symptoms, although the biological mechanisms underpinning this effect are incompletely understood. Numerous lines of evidence support inflammation and oxidative and nitrogen stress (O&NS) as important in the pathogenesis of mood and anxiety disorders, and physical activity is known to influence these same pathways. This paper reviews the inter-relationships between anxiety disorders, physical activity and inflammation and O&NS, to explore whether modulation of inflammation and O&NS may in part underpin the positive effect of physical activity on anxiety disorders. Numerous studies support the notion that physical activity operates as an anti-inflammatory and anti-O&NS agent which potentially exerts positive effects on neuroplasticity, the expression of neurotrophins and normal neuronal functions. These effects may therefore influence the expression and evolution of anxiety disorders. Further exploration of this area may elicit a deeper understanding of the pathogenesis of anxiety disorders, and inform the development of integrated programmes including PA specifically suited to the treatment and prevention of anxiety disorders and symptoms.
Publisher: Public Library of Science (PLoS)
Date: 05-02-2016
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.JAD.2007.03.007
Abstract: Staging models are widely used in clinical medicine, and offer an insight into the progressive nature of many disorders. In general, the earlier stages of illness may be associated with a better prognosis and a higher treatment response. Once chronicity is reached, more complex and invasive treatments may be required, and the utility of treatments may decline. There is evidence that treatment response is greatest in the early phases of the disorder. There is also a progressive social and psychological burden of ongoing illness. This is paralleled by the twin notions of neuroprotection, which is supported by increasing evidence that structural changes in the disorder may be progressive and reversible with algorithm appropriate treatment, and that of early intervention, which posits that the optimal window for intervention is early in the illness course. A staging model compliments existing and proposed classifications of bipolar disorder, adding a temporal dimension to a cross sectional view. It may inform treatment choice and prognosis, and could have utility as a course specifier.
Publisher: Wiley
Date: 05-2018
DOI: 10.1111/BDI.12641
Publisher: Informa UK Limited
Date: 29-04-2020
Publisher: SAGE Publications
Date: 05-2010
DOI: 10.3109/00048670903571598
Abstract: Objective: Adolescence frequently coincides with the onset of psychiatric illness and depression is commonly observed in adolescents. Recent data suggest a role for diet quality in adult depression. Given the importance of adequate nutrition for brain development, it is of interest to examine whether diet quality is also related to depression in adolescents. Methods: The study examined 7114 adolescents, aged 10–14 years, who participated in the Australian Healthy Neighbourhoods Study. Healthy and unhealthy diet quality scores were derived from a dietary questionnaire. The Short Mood and Feelings Questionnaire for adolescents measured depression. Adjustments were made for age, gender, socioeconomic status, parental education, parental work status, family conflict, poor family management, dieting behaviours, body mass index, physical activity, and smoking. Results: Compared to the lowest category of the healthy diet score, the adjusted odds ratios (95% confidence interval) for symptomatic depression across categories (C) was: C2 = 0.61 (0.45–0.84) C3 = 0.58 (0.43–0.79) C4 = 0.47 (0.35–0.64) and C5 = 0.55 (0.40–0.77). Compared to the lowest quintile, the adjusted odds ratios (95% confidence interval) for symptomatic depression across increasing quintiles of the unhealthy diet score were: Q2 = 1.03 (0.87–1.22) Q3 = 1.22 (1.03–1.44) Q4 = 1.29 (1.12–1.50) and Q5 = 1.79 (1.52–2.11). Conclusions: Our results demonstrate an association between diet quality and adolescent depression that exists over and above the influence of socioeconomic, family, and other potential confounding factors.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.BONE.2015.12.015
Abstract: Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged in iduals at greater risk of osteoporotic fracture. Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed. Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce in idual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups. Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged in iduals at greater risk of osteoporosis.
Publisher: Springer Science and Business Media LLC
Date: 06-03-2018
DOI: 10.1038/S41398-018-0108-8
Abstract: Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal ( p = 0.05) and caudal ( p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus ( p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). www.anzctr.org.au
Publisher: SAGE Publications
Date: 28-06-2020
Publisher: Cambridge University Press (CUP)
Date: 16-07-2018
DOI: 10.1017/NEU.2018.13
Abstract: This study aimed to explore effects of adjunctive treatment with N -acetyl cysteine (NAC) on markers of inflammation and neurogenesis in bipolar depression. This is a secondary analysis of a placebo-controlled randomised trial. Serum s les were collected at baseline, week 8, and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following adjunctive NAC treatment, and to explore mediation and moderator effects of the listed markers. Levels of brain-derived neurotrophic factor (BDNF), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukins (IL) -6, 8, or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases. There were no mediation or moderation effects of the biological factors on the clinical parameters. The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.EURONEURO.2021.10.002
Abstract: Smoking represents a significant health threat to the population, however there remains a core group of consistent smokers that are largely unable to break the addiction. Novel therapies are required to assist this group with cessation. N-acetylcysteine (NAC) is a nutraceutical supplement that has shown efficacy compared to placebo in previous pilot studies for assisting smokers to quit or reduce their consumption of cigarettes. A double-blind, randomised trial with a treatment period of 16 weeks and a final follow-up at 42 weeks was conducted comparing 1.8g of effervescent NAC per day (n=47) with placebo (n=47) as an aide to smoking cessation. Both study arms received adjunctive online support through the QuitCoach program. Participants reported smoking at each timepoint (baseline and weeks 8, 16 & 42), which was confirmed through salivary cotinine and exhaled carbon monoxide testing. Primary and secondary analyses were undertaken using a modified intent-to-treat basis, including all participants with at least one valid post baseline outcome, regardless of treatment received or their withdrawal from the study. There was no significant difference in smoking outcomes between intervention groups among the 24 participants that competed follow-up. There were no significant differences in age, gender, or body mass index (BMI) between the groups lost to follow-up or recorded at follow-up. This study found no evidence to support NAC as a therapy for smoking cessation. The negative outcome could be the result of lack of treatment efficacy, or alternatively, small s le size, participant retention difficulties, dose, or duration of follow-up. Trial Registration: Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12617001478303. Registered on 19 October 2017.
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.SCHRES.2007.02.022
Abstract: mRNA for 14-3-3zeta, an abundant signalling protein in human CNS, is reported as decreased or unchanged in cortex from subjects with schizophrenia. Addressing this dichotomy, using Western blot analyses, we measured levels of 14-3-3zeta proteins in cortex and caudate nucleus from subjects with schizophrenia, bipolar disorder, age/sex matched controls and in analogous CNS regions from rats treated with psychotropic drugs. Anti-14-3-3zeta antibody bound to three proteins (molecular weights: 27, 54 and 70 kDa), in all CNS tissue. Levels of all proteins did not vary with diagnoses (27 kDa: F(2,42.0)=0.35, p=0.71 54 kDa: F(2,42.1)=0.62, p=0.54 70 kDa: F(2,41.0)=2.43, p=0.10). By contrast, independent of diagnoses, there were significant increases in the levels of the 27 kDa protein (+32% p<0.001) and 54 kDa protein (51% p=0.001) in the caudate nucleus from males compared to females. In addition, there was a trend (-25% p=0.06) to decreased levels of the 70 kDa protein in BA 9 in males compared to females. Treating with haloperidol, olanzapine, lithium or a combination thereof did not alter 14-3-3zeta levels in rat cortex or striatum. Therefore, this study suggests that 14-3-3zeta proteins are not altered in the cortex or caudate nucleus in schizophrenia, bipolar disorder or in analogous regions in psychotropic drug treated rats. By contrast, our study suggests that levels of 14-3-3zeta in some regions of the human CNS may be modulated by some sex-specific mechanism.
Publisher: Cambridge University Press (CUP)
Date: 2017
DOI: 10.1016/J.EURPSY.2016.06.003
Abstract: Key lifestyle-environ risk factors are operative for depression, but it is unclear how risk factors cluster. Machine-learning (ML) algorithms exist that learn, extract, identify and map underlying patterns to identify groupings of depressed in iduals without constraints. The aim of this research was to use a large epidemiological study to identify and characterise depression clusters through “Graphing lifestyle-environs using machine-learning methods” (GLUMM). Two ML algorithms were implemented: unsupervised Self-organised mapping (SOM) to create GLUMM clusters and a supervised boosted regression algorithm to describe clusters. Ninety-six “lifestyle-environ” variables were used from the National health and nutrition examination study (2009–2010). Multivariate logistic regression validated clusters and controlled for possible sociodemographic confounders. The SOM identified two GLUMM cluster solutions. These solutions contained one dominant depressed cluster (GLUMM5-1, GLUMM7-1). Equal proportions of members in each cluster rated as highly depressed (17%). Alcohol consumption and demographics validated clusters. Boosted regression identified GLUMM5-1 as more informative than GLUMM7-1. Members were more likely to: have problems sleeping unhealthy eating ≤ 2 years in their home an old home perceive themselves underweight exposed to work fumes experienced sex at ≤ 14 years not perform moderate recreational activities. A positive relationship between GLUMM5-1 (OR: 7.50, P 0.001) and GLUMM7-1 (OR: 7.88, P 0.001) with depression was found, with significant interactions with those married/living with partner ( P = 0.001). Using ML based GLUMM to form ordered depressive clusters from multitudinous lifestyle-environ variables enabled a deeper exploration of the heterogeneous data to uncover better understandings into relationships between the complex mental health factors.
Publisher: Wiley
Date: 12-11-2004
DOI: 10.1111/J.1399-5618.2004.00154.X
Abstract: The treatment alliance is the arena in which psychopharmacological and other therapeutic interventions occur. The nature and quality of the treatment alliance may affect adherence to treatment and the realization of the benefits of effective pharmacological treatment in clinical practice. It is an area that has attracted little systematic study, despite the available evidence suggesting that it plays a measurable role in clinical outcomes. A literature search was undertaken using Medline, Ovid, Psychinfo and Science Direct from 1975 to 2004. The following key words were used: bipolar disorder, patient adherence, non-adherence to medication, compliance, doctor-patient relationship, doctor-patient communication, treatment alliance, therapeutic alliance, chronic illness management, collaborative care, self-management, health beliefs, self-efficacy, self-determination, autonomy support, motivational interviewing. Psychosocial interventions have demonstrated positive effects on adherence problems. Studies of the impact of the treatment alliance on outcomes in mental illness highlight the possibilities of fruitful research in this area in bipolar disorder. Different theoretical models of changing health related behaviour may inform approaches to the treatment alliance. Results suggest the usefulness of a collaborative approach to the treatment alliance. Attention needs to be given to developing intervention models that target modifiable risk factors for non-adherence and address patient, clinician and illness related variables to enhance medication adherence in the treatment alliance. Refinement of these models through controlled evaluation in real world settings may lead to integration in health care delivery systems.
Publisher: Wiley
Date: 10-07-2009
DOI: 10.1111/J.1399-5618.2009.00726.X
Abstract: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2017
DOI: 10.1007/S11011-017-0144-8
Abstract: There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippoc al monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippoc al 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippoc al lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippoc al lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.
Publisher: EDITORA SCIENTIFIC
Date: 05-2019
Publisher: American Medical Association (AMA)
Date: 06-11-2018
Publisher: Informa UK Limited
Date: 03-2013
DOI: 10.1080/13548506.2012.689840
Abstract: We describe the development process and completed structure, of a self-help online intervention for bipolar disorder, known as MoodSwings ( www.moodswings.net.au) . The MoodSwings program was adapted as an Internet intervention from an efficacious and validated face-to-face, group-based psychosocial intervention. The adaptation was created by a psychologist, who had previously been involved with the validation of the face-to-face program, in collaboration with website designers. The project was conducted under the supervision of a team of clinician researchers. The website is available at no cost to registered participants. Self-help modules are accessed sequentially. Other features include a mood diary and a moderated discussion board. There has been an average of 1,475,135 hits on the site annually (2008 and 2009), with some 7400 unique visitors each year. A randomised controlled trial based on this program has been completed. Many people with bipolar disorder are accepting of the Internet as a source of treatment and, once engaged, show acceptable retention rates. The Internet appears to be a viable means of delivering psychosocial self-help strategies.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2020
DOI: 10.1038/S41398-020-0836-4
Abstract: Precision psychiatry is attracting increasing attention lately as a recognized priority. One of the goals of precision psychiatry is to develop tools capable of aiding a clinically informed psychiatric diagnosis objectively. Cognitive, inflammatory and immunological factors are altered in both bipolar disorder (BD) and schizophrenia (SZ), however, most of these alterations do not respect diagnostic boundaries from a phenomenological perspective and possess great variability in different in iduals with the same phenotypic diagnosis and, consequently, none so far has proven to have the ability of reliably aiding in the differential diagnosis of BD and SZ. We developed a probabilistic multi-domain data integration model consisting of immune and inflammatory biomarkers in peripheral blood and cognitive biomarkers using machine learning to predict diagnosis of BD and SZ. A total of 416 participants, being 323, 372, and 279 subjects for blood, cognition and combined biomarkers analysis, respectively. Our multi-domain model performances for the BD vs. control (sensitivity 80% and specificity 71%) and for the SZ vs. control (sensitivity 84% and specificity 81%) pairs were high in general, however, our multi-domain model had only moderate performance for the differential diagnosis of BD and SZ (sensitivity 71% and specificity 73%). In conclusion, our results show that the diagnosis of BD and of SZ, and that the differential diagnosis of BD and SZ can be predicted with possible clinical utility by a computational machine learning algorithm employing blood and cognitive biomarkers, and that their integration in a multi-domain outperforms algorithms based in only one domain. Independent studies are needed to validate these findings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
Publisher: Cambridge University Press (CUP)
Date: 21-06-2021
DOI: 10.1017/S1092852921000638
Abstract: Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N -acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium. A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks. An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit ( P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.YMETH.2014.07.001
Abstract: The exponential increase in data, computing power and the availability of readily accessible analytical software has allowed organisations around the world to leverage the benefits of integrating multiple heterogeneous data files for enterprise-level planning and decision making. Benefits from effective data integration to the health and medical research community include more trustworthy research, higher service quality, improved personnel efficiency, reduction of redundant tasks, facilitation of auditing and more timely, relevant and specific information. The costs of poor quality processes elevate the risk of erroneous outcomes, an erosion of confidence in the data and the organisations using these data. To date there are no documented set of standards for best practice integration of heterogeneous data files for research purposes. Therefore, the aim of this paper is to describe a set of clear protocol for data file integration (Data Integration Protocol In Ten-steps DIPIT) translational to any field of research. The DIPIT approach consists of a set of 10 systematic methodological steps to ensure the final data are appropriate for the analysis to meet the research objectives, legal and ethical requirements are met, and that data definitions are clear, concise, and comprehensive. This protocol is neither file specific nor software dependent, but aims to be transportable to any data-merging situation to minimise redundancy and error and translational to any field of research. DIPIT aims to generate a master data file that is of the optimal integrity to serve as the basis for research analysis. With linking of heterogeneous data files becoming increasingly common across all fields of medicine, DIPIT provides a systematic approach to a potentially complex task of integrating a large number of files and variables. The DIPIT protocol will ensure the final integrated data is consistent and of high integrity for the research requirements, useful for practical application across all fields of medical research.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2022
DOI: 10.1038/S41380-021-01306-8
Abstract: Depression onset peaks during adolescence and young adulthood. Current treatments are only moderately effective, driving the search for novel pathophysiological mechanisms underlying youth depression. Inflammatory dysregulation has been shown in adults with depression, however, less is known about inflammation in youth depression. This systematic review identified 109 studies examining the association between inflammation and youth depression and showed subtle evidence for inflammatory dysregulation in youth depression. Longitudinal studies support the bidirectional association between inflammation and depression in youth. We hypothesise multiple inflammatory pathways contributing to depression. More research is needed on anti-inflammatory treatments, potentially tailored to in idual symptom profiles.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2016
Publisher: Springer Science and Business Media LLC
Date: 21-06-2016
DOI: 10.1038/TP.2016.84
Abstract: Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg −1 ) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST ( P .05). NAc DBS effectively improved FST mobility in ACTH-treated animals ( P .05). No improvement in mobility was observed for sham control animals ( P .05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation.
Publisher: Wiley
Date: 04-10-2023
DOI: 10.1111/EIP.13353
Abstract: Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non‐medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids. This study utilized data from a triple‐blind randomized placebo‐controlled trial comparing two groups of antipsychotic‐naïve young people with a FEP who were randomized to receive a second‐generation antipsychotic medication (FEP‐medication group) or placebo (FEP‐placebo group) for 6 months. Twenty‐seven control participants were also recruited. Eighty‐one participants commenced the trial 69.1% completed at least 3 months of the intervention and 33.3% completed the full 6 months. The FEP‐placebo group gained a mean of 2.4 kg (±4.9) compared to 1.1 kg (±4.9) in the control participants ( t = 0.76, p = .45). After controlling for multiple analyses, there was no difference in blood pressure, waist circumference or heart rate between the FEP‐placebo group and controls. After 6 months, the FEP medication group had gained 4.1 kg (±4.5), higher than those receiving placebo but not statistically significant ( t = 0.8, p = .44). There were no differences in fasting glucose or lipids between the FEP groups after 3 months. While limited by small numbers and high attrition, these findings indicate that some of the metabolic complications observed in psychotic disorders could be attributable to factors other than medication. This emphasizes the need to deliver physical health interventions early in the course of FEP.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2016
Publisher: Wiley
Date: 05-2010
DOI: 10.1111/J.1399-5618.2010.00813.X
Abstract: To assess the prevalence and correlates of childhood and adolescent sexual and/or physical abuse (SPA) in bipolar I disorder (BDI) patients treated for a first episode of psychotic mania. The Early Psychosis Prevention and Intervention Centre admitted 786 first-episode psychosis patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. A total of 704 files were available 43 were excluded because of a nonpsychotic diagnosis at endpoint and 3 due to missing data regarding past stressful events. Among 658 patients with available data, 118 received a final diagnosis of BDI and were entered in this study. A total of 80% of patients had been exposed to stressful life events during childhood and adolescence and 24.9% to SPA in particular, 29.8% of female patients had been exposed to sexual abuse. Patients who were exposed to SPA had poorer premorbid functioning, higher rates of forensic history, were less likely to live with family during treatment period, and were more likely to disengage from treatment. SPA is highly prevalent in BDI patients presenting with a first episode of psychotic mania exposed patients have lower premorbid functional levels and poorer engagement with treatment. The context in which such traumas occur must be explored in order to determine whether early intervention strategies may contribute to diminish their prevalence. Specific psychological interventions must also be developed.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JAD.2019.06.060
Abstract: Seasonal Affective Disorder (SAD) is a form of cyclic mood disorder that tends to manifest as winter depression. SAD has anecdotally been described as a hypocortisolemic condition. However, there are no systematic reviews on SAD and Hypothalamic-Pituitary-Adrenal (HPA) axis function. This review intends to summarize these findings. Using the PRISMA (2009) guideline recommendations we searched for relevant articles indexed in databases including MEDLINE, EMBASE, PsycINFO, and PsychArticles. The following keywords were used: "Seasonal affective disorder", OR "Winter Depression", OR "Seasonal depression" associated with: "HPA Axis" OR "cortisol" OR "CRH" OR "ACTH". Thirteen papers were included for qualitative analysis. Studies used both heterogeneous methods and populations. The best evidence comes from a recent study showing that SAD patients tend to demonstrate an attenuated Cortisol Awakening Response (CAR) in winter, but not in summer, compared to controls. Dexamethasone Suppression Test (DST) studies suggest SAD patients have normal suppression of the HPA axis. There is still insufficient evidence to classify SAD as a hypocortisolemic condition when compared to controls. Heterogeneous methods and s les did not allow replication of results. We discuss the limitations of these studies and provide new methods and targets to probe HPA axis function in this population. SAD can provide a unique window of opportunity to study HPA axis in affective disorders, since it is highly predictable and can be followed before, during and after episodes subsides.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2012
DOI: 10.1038/MP.2012.33
Abstract: In some patients with major depressive disorder (MDD), in idual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic-pituitary-adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed.
Publisher: SAGE Publications
Date: 22-03-2013
Abstract: To examine the cross-sectional association between overweight and obesity and positive and negative affect. Participants included 273 women, aged 29–84 years, who were enrolled in the Geelong Osteoporosis Study (GOS). Weight and height were measured and overweight and obesity determined from body mass index (BMI kg/m 2 ) according to WHO criteria. Medical history and lifestyle exposures were assessed by questionnaire. Positive and negative affect scores were derived using the validated 20-item Positive and Negative Affect Schedule (PANAS) and categorised into tertiles. A pattern of greater negative affect scores was observed for increasing levels of BMI. Setting normal weight as the referent category, the odds for having a negative affect score in the highest tertile were sequentially increased for women who were overweight (OR = 1.31, 95% CI: 0.72–2.40) and obese (OR = 1.95, 95% CI: 1.02–3.73). The association between obesity and increased negative affect was diminished by adjusting for physical illness (adjusted OR = 1.76, 95% CI: 0.91–3.42). These associations were not substantially influenced by positive affect score or other exposures. No association was detected between BMI categories and positive affect scores. We report data suggesting that obesity is associated with greater negative affect scores, reflecting emotions such as distress, anger, disgust, fear and shame, and that this association is attenuated by physical illness. Further investigations are now warranted to explore possible mechanistic interplay between pathological, neurobiological and psychosocial factors.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2021
Publisher: Wiley
Date: 12-2011
DOI: 10.1002/HUP.1253
Abstract: A significant proportion of subjects drop out of medium to long-term clinical studies prior to trial completion. This may bias reported study outcomes and reduce the statistical power of analyses. There is therefore a need for researchers to better understand the characteristics of dropout populations to increase completion rates. Data from a set of participants recruited as part of a 24-week placebo-controlled trial were used to determine the relationship between the five Lindenmayer factors of positive, negative, cognitive, anxiety/depression and excitement symptoms and dropout at trial completion. Results indicated that the rate of trial dropout was significantly predicted by scores on the negative Lindenmayer factor (X² (6, N = 126) = 15.60, p < .05). By trial completion, participants with 'high' negative Lindenmayer scores dropped out at a rate of 64%, whereas 'medium' and 'low' groups dropped out at 43% and 30%, respectively. No other relationship between symptom severity scores and dropout across the remaining Lindenmayer factors was found. These findings reflect important considerations for the future design of clinical trials involving people with schizophrenia and may also provide clues into treatment compliance issues more generally.
Publisher: Wiley
Date: 23-03-2023
DOI: 10.1111/BDI.13319
Abstract: The aim of this study was to repurpose a drug for the treatment of bipolar depression. A gene expression signature representing the overall transcriptomic effects of a cocktail of drugs widely prescribed to treat bipolar disorder was generated using human neuronal‐like (NT2‐N) cells. A compound library of 960 approved, off‐patent drugs were then screened to identify those drugs that affect transcription most similar to the effects of the bipolar depression drug cocktail. For mechanistic studies, peripheral blood mononuclear cells were obtained from a healthy subject and reprogrammed into induced pluripotent stem cells, which were then differentiated into co‐cultured neurons and astrocytes. Efficacy studies were conducted in two animal models of depressive‐like behaviours (Flinders Sensitive Line rats and social isolation with chronic restraint stress rats). The screen identified trimetazidine as a potential drug for repurposing. Trimetazidine alters metabolic processes to increase ATP production, which is thought to be deficient in bipolar depression. We showed that trimetazidine increased mitochondrial respiration in cultured human neuronal‐like cells. Transcriptomic analysis in induced pluripotent stem cell‐derived neuron/astrocyte co‐cultures suggested additional mechanisms of action via the focal adhesion and MAPK signalling pathways. In two different rodent models of depressive‐like behaviours, trimetazidine exhibited antidepressant‐like activity with reduced anhedonia and reduced immobility in the forced swim test. Collectively our data support the repurposing of trimetazidine for the treatment of bipolar depression.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Korean College of Neuropsychopharmacology
Date: 30-05-2023
Publisher: Cambridge University Press (CUP)
Date: 10-2007
Publisher: Wiley
Date: 04-2009
DOI: 10.1002/HUP.1017
Abstract: Schizophrenia is a multifaceted illness with positive, negative and cognitive symptom domains. Standard treatments often focus on positive symptoms and may not adequately relieve other symptoms. Previous studies have suggested a role for mirtazapine in schizophrenia, particularly in negative symptoms. This study investigates the efficacy of adding mirtazapine to treatment as usual to alleviate the negative symptoms of schizophrenia. In a 6 week, double-blind clinical trial, participants with a diagnosis of schizophrenia and currently being treated with atypical antipsychotic medication were randomised to adjunctive treatment with mirtazapine (30 mg/day) or placebo. The primary outcome measure was improvement in the Positive and Negative Syndrome Scale (PANSS). Measures of cognition, collected at baseline and week 6 only, were analysed using an Analysis of Covariance (ANCOVA) model. All other outcome measures were analysed using a linear mixed model. Forty participants were recruited to the study with equal numbers randomised to each treatment arm. There was no significant difference between mirtazapine and placebo treated participants for improvement in PANSS scores or any of the secondary outcome measures at any stage during the 6-week trial. This trial does not confirm previous research supporting the use of mirtazapine adjunctive to atypical antipsychotic treatment for schizophrenia.
Publisher: Wiley
Date: 04-07-2008
DOI: 10.1111/J.1399-5618.2008.00610.X
Abstract: Affective psychoses and bipolar disorders have been neglected in the development of early intervention strategies. This paper aims to gather current knowledge on the early phase of bipolar disorders in order to define new targets for early intervention. Literature review based on the main computerized databases (MEDLINE, PUBMED and PSYCHLIT) and hand search of relevant literature. Based on current knowledge, it is likely that an approach aiming at the identification of impending first-episode mania is the most realistic and manageable strategy to promote earlier treatment. During the period preceding the onset of the first manic episode, patients go through a prodromal phase marked by the presence of mood fluctuation, sleep disturbance, and other symptoms such as irritability, anger, or functional impairment. Additionally, various risk factors and markers of vulnerability to bipolar disorders have been identified. In the few months preceding first-episode mania, patients go through a prodrome phase (proximal prodrome) that could become an important target for early intervention. However, considering the low specificity of the symptoms observed during this phase, criteria defining high-risk profiles to first-episode mania should also include certain risk factors or markers of vulnerability. While more research is needed in high-risk groups (e.g., bipolar offspring), retrospective studies conducted in first-episode mania cohorts could provide valuable information about this critical phase of the illness.
Publisher: Public Library of Science (PLoS)
Date: 09-12-2016
Publisher: Cambridge University Press (CUP)
Date: 15-07-2022
DOI: 10.1017/S1092852922000906
Abstract: This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2021
Publisher: Elsevier BV
Date: 08-2021
Publisher: JMIR Publications Inc.
Date: 16-12-2016
DOI: 10.2196/JMIR.5870
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.JAD.2010.06.016
Abstract: We have developed ultra-high risk criteria for bipolar affective disorder (bipolar at-risk - BAR) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania, depressive symptoms, cyclothymic features and genetic risk. In the current study, the predictive validity of these criteria were tested in help-seeking adolescents and young adults. This medical file-audit study was conducted at ORYGEN Youth Health (OYH), a public mental health program for young people aged between 15 and 24years and living in metropolitan Melbourne, Australia. BAR criteria were applied to the intake assessments of all non-psychotic patients who were being treated in OYH on 31 January, 2008. All entries were then checked for conversion criteria. Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania. The BAR criteria were applied to 173 intake assessments. Of these, 22 patients (12.7%) met BAR criteria. The follow-up period of the s le was 265.5days on average (SD 214.7). There were significantly more cases in the BAR group (22.7%, n=5) than in the non-BAR group (0.7%, n=1) who met conversion criteria (p<.001). These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase. The proposed criteria need further evaluation in prospective clinical trials.
Publisher: Cambridge University Press (CUP)
Date: 08-2009
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.JAD.2008.01.018
Abstract: This study aimed to compare the treatment responses between smokers and non-smokers in bipolar mania clinical trials. Post-hoc analysis was conducted on data collected from three double-blind, randomised controlled trials in bipolar mania that had similar inclusion criteria. Patients were randomised to olanzapine (N=70) or placebo (N=69) for 3 weeks in Trial 1, olanzapine (N=234) or haloperidol (N=216) for 12 weeks in Trial 2, and olanzapine (N=125) or alproex (N=126) for 47 weeks in Trial 3. This study analysed the Young Mania Rating Scale (YMRS) total scores and Clinical Global Impressions scale for bipolar disorder (CGI-BP) mania severity scores between smokers and non-smokers for each trial and for the pooled data from all three trials, using a mixed-effects model repeated measures approach. For the pooled data, non-smokers showed superior treatment outcomes on both the YMRS (P=0.002) and CGI-BP (P<0.001), as well as longer time to discontinuation for any cause utilising Kaplan-Meier survival curves. For the in idual trials, non-smokers showed greater improvement than smokers on both CGI-BP and YMRS in both treatment arms of Trial 2 (CGI-BP: haloperidol P=0.011, olanzapine P=0.042 YMRS: haloperidol P=0.010, olanzapine P=0.019), and in the olanzapine arm of Trial 3 (CGI-BP: P=0.002 YMRS: P=0.006). No significant difference in outcomes was found between smokers and non-smokers in Trial 1. Post-hoc design, categorical definition of smoking status, unavailable antipsychotic drug levels, confounding effects of trial medications and substance abuse. Smoking appears to be associated with worse treatment outcomes in mania.
Publisher: Wiley
Date: 11-2007
DOI: 10.1111/J.1399-5618.2007.00484.X
Abstract: Bipolar disorder is common, and both difficult to detect and diagnose. Treatment is contingent on clinical needs, which differ according to phase and stage of the illness. A staging model could allow examination of the longitudinal course of the illness and the temporal impact of interventions and events. It could allow for a structured examination of the illness, which could set the stage for algorithms that are tailored to the in iduals needs. A staging model could further provide as structure for assessment, gauging treatment and outcomes. The model incorporates prodromal stages and emphasizes early detection and algorithm appropriate intervention where possible. At the other end of the spectrum, the model attempts to operationalize treatment resistance. The utility of the model will need to be validated by empirical research.
Publisher: Oxford University Press (OUP)
Date: 29-08-2022
DOI: 10.1093/IJNP/PYAC057
Abstract: The prevalence of posttraumatic stress disorder (PTSD) co-occurring in people with bipolar disorder (BD) is high. People with BD and PTSD may experience different outcomes and quality of life after pharmacologic treatment than those with BD alone. This review systematically explores the impact of PTSD on pharmacologic treatment outcomes for adults with BD. We conducted a systematic search up to November 25, 2021, using MEDLINE Complete, Embase, American Psychological Association PsycInfo, and the Cochrane Central Register of Controlled Trials to identify randomized and nonrandomized studies of pharmacologic interventions for adults with BD that assessed for comorbid PTSD. We used the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool to assess the risk of bias. The search identified 5093 articles, and we reviewed 62 full-text articles. Two articles met inclusion criteria (N = 438). One article was an observational study, and the other was a randomized comparative effectiveness trial. The observational study examined lithium response rates and found higher response rates in BD alone compared with BD plus PTSD over 4 years. The randomized trial reported more severe symptoms in the BD plus PTSD group than in those with BD alone following 6 months of quetiapine treatment. There was no significant difference in the lithium treatment group at follow-up. Comorbid PTSD may affect quetiapine and lithium treatment response in those with BD. Because of the high risk of bias and low quality of evidence, however, these results are preliminary. Specific studies exploring comorbid BD and PTSD are required to inform pharmacotherapy selection and guidelines appropriately. (International Prospective Register of Systematic Reviews ID: CRD42020182540).
Publisher: Frontiers Media SA
Date: 08-04-2022
DOI: 10.3389/FPHAR.2022.873271
Abstract: Long non-coding RNAs (lncRNAs) may play a role in psychiatric diseases including bipolar disorder (BD). We investigated mRNA-lncRNA co-expression patterns in neuronal-like cells treated with widely prescribed BD medications. The aim was to unveil insights into the complex mechanisms of BD medications and highlight potential targets for new drug development. Human neuronal-like (NT2-N) cells were treated with either lamotrigine, lithium, quetiapine, valproate or vehicle for 24 h. Genome-wide mRNA expression was quantified for weighted gene co-expression network analysis (WGCNA) to correlate the expression levels of mRNAs with lncRNAs. Functional enrichment analysis and hub lncRNA identification was conducted on key co-expressed modules associated with the drug response. We constructed lncRNA-mRNA co-expression networks and identified key modules underlying these treatments, as well as their enriched biological functions. Processes enriched in key modules included synaptic vesicle cycle, endoplasmic reticulum-related functions and neurodevelopment. Several lncRNAs such as GAS6-AS1 and MIR100HG were highlighted as driver genes of key modules. Our study demonstrates the key role of lncRNAs in the mechanism(s) of action of BD drugs. Several lncRNAs have been suggested as major regulators of medication effects and are worthy of further investigation as novel drug targets to treat BD.
Publisher: Springer Science and Business Media LLC
Date: 25-05-2019
Publisher: American Psychiatric Association Publishing
Date: 12-2021
Publisher: Springer Science and Business Media LLC
Date: 18-03-2022
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.BBR.2012.12.033
Abstract: Several animal models are currently utilised in the investigation of major depressive disorder however, each is validated by its response to antidepressant pharmacotherapy. Few animal models consider the notion of antidepressant treatment resistance. Chronic daily administration of adrenocorticotropic hormone (ACTH) or corticosterone can alter behavioural responses to antidepressants, effectively blocking antidepressant efficacy. Herein, we demonstrate that ACTH-(1-24) (100μg/day 14 days) blocks the immobility-reducing 'antidepressant' effects of a single dose of imipramine (10mg/kg) in the forced swim test. This finding was accompanied by altered monoamine tissue levels in the prefrontal cortex (PFC) 1h after exposure to the acute stress of the forced swim test. PFC tissue from ACTH pre-treated animals contained significantly higher serotonin, noradrenaline and adrenaline concentrations relative to saline pre-treated controls. Conversely, dopamine levels were significantly decreased. Altered plasma corticosterone responses to ACTH injections were observed over the treatment course. Measures were taken on treatment days 1, 4, 8, 11, 14 and 15. ACTH administration initially enhanced plasma corticosterone levels, however, these normalised to levels consistent with control animals by day 14. No differences in corticosterone levels were observed across the treatment time course in saline-treated animals. Taken together these results indicate that pre-treatment with ACTH (100μg/day 14 days) blocks the antidepressant effects of imipramine (10mg/kg), significantly alters key PFC monoamine responses to stress and downregulates glucocorticoid responses. These results suggest that chronic ACTH treatment is a promising paradigm for elucidation of mechanisms mediating antidepressant treatment resistance.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.METABOL.2014.09.011
Abstract: Excessive daytime sleepiness (EDS) has been associated with singular independent symptoms of metabolic syndrome, such as insulin resistance and diabetes. The aim of this study was to assess whether this relationship is sustained among in iduals who meet criteria for the whole syndrome. 994 Women aged 21-94 years (median 50.2 years, IQR 34-65) and 840 men aged 24-92 years (median 60.4 years, IQR 47-73) who resided in the Barwon Statistical Division, South-Eastern Australia, and participated in the Geelong Osteoporosis Study (GOS) between the years of 2001 and 2008. Anthropometric measurements, lifestyle, mood, demographic and health-related factors were obtained. Sleep duration was categorized as short ( 9 h). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and scores of ≥ 10 indicated EDS. The presence of metabolic syndrome was assessed using a modified version of criteria as outlined by the International Diabetics Federations recommendations (2005). Women: 138 (14.0%) of the women reported EDS those with EDS were heavier, had a greater body mass index (BMI) and were more likely to have metabolic syndrome. The association between EDS and metabolic syndrome was sustained following adjustment for age and hours sleep (adjusted OR=1.90, 95% CI 1.16-3.09), however BMI attenuated the relationship (adjusted OR=1.64, 95% CI =1.05-2.57). These findings were independent of smoking status, alcohol intake, medication use, socioeconomic status, physical activity and current diagnosis of a depressive illness. Men: 111 (13.2%) of the men reported EDS those with EDS had a greater waist circumference and were more likely to have metabolic syndrome. Analysis of age-stratified data (<60 years vs. ≥60 years) revealed that the older men with EDS were more likely to have metabolic syndrome (OR=1.71, 95% CI 1.01-2.92), however, age explained this association (age adjusted OR=1.51, 95% CI 0.88-2.60). In the younger age group, no association was detected between EDS and metabolic syndrome. For both men and women, the prevalence of combined EDS and metabolic syndrome increased progressively with age. For women, the association between EDS and metabolic syndrome appears to be driven by adiposity measures while for men, the association is somewhat attributed to older age. Additional research is required to assess temporal associations with underlying sleep pathology.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2011
DOI: 10.1038/MP.2011.167
Publisher: Wiley
Date: 24-11-2010
DOI: 10.1111/J.1600-0447.2010.01638.X
Abstract: The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls. Meta-analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls. In iduals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains. Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness.
Publisher: SAGE Publications
Date: 12-2011
DOI: 10.3109/00048674.2011.621063
Abstract: Objective: The aim of ths study was to examine the association between habitual physical activity and positive and negative affect. Method: This cross-sectional study included 276 women aged 20 +, from the Geelong Osteoporosis Study. Habitual physical activity and other lifestyle exposures were assessed by questionnaire, concurrent with anthropometric assessments. Physical activity was categorized as very active, moderately active or sedentary. Positive and negative affect scores were derived from the validated 20 item Positive and Negative Affect Schedule (PANAS) self-report and were categorized into tertiles. Results: There was a pattern of lower positive affect scores for lower levels of physical activity. With very active as the reference category, the odds for having a positive affect score in the highest tertile were sequentially lower for those who were moderately active (OR = 0.53, 95%CI 0.28–1.01) and sedentary (OR = 0.28, 95%CI 0.10–0.75). Associations were sustained after adjusting for body mass index and polypharmacy (OR = 0.50, 95%CI 0.26–0.96 and OR = 0.25, 95%CI 0.09–0.72, respectively). These associations were not explained by age, negative affect score or other exposures. No association was detected between physical activity and negative affect scores. Conclusions: This study reports that higher positive affect scores, encompassing emotions such as interest, excitement, enthusiasm and alertness, are associated with higher levels of habitual physical activity. These observations warrant further investigations into possible mechanistic interplay between neurobiological and psychosocial factors that underpin this association.
Publisher: Korean College of Neuropsychopharmacology
Date: 30-04-2015
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.TIPS.2008.05.001
Abstract: There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in erse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders. This article outlines the multidimensional evidence that currently exists for oxidative stress mechanisms in psychiatric disorders and specifically discusses glutathione as a promising novel therapeutic target.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.PNPBP.2016.09.004
Abstract: Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for ex le, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2013
Publisher: Georg Thieme Verlag KG
Date: 28-09-2022
DOI: 10.1055/A-1936-3580
Abstract: Introduction Mood disorders are a major cause of disability, and current treatment options are inadequate for reducing the burden on a global scale. The aim of this project was to identify drugs suitable for repurposing to treat mood disorders. Methods This mixed-method study utilized gene expression signature technology and pharmacoepidemiology to investigate drugs that may be suitable for repurposing to treat mood disorders. Results The transcriptional effects of a combination of drugs commonly used to treat mood disorders included regulation of the steroid and terpenoid backbone biosynthesis pathways, suggesting a mechanism involving cholesterol biosynthesis, and effects on the thyroid hormone signaling pathway. Connectivity Map analysis highlighted metformin, an FDA-approved treatment for type 2 diabetes, as a drug having global transcriptional effects similar to the mood disorder drug combination investigated. In a retrospective cohort study, we found evidence that metformin is protective against the onset of mood disorders. Discussion These results provide proof-of-principle of combining gene expression signature technology with pharmacoepidemiology to identify potential novel drugs for treating mood disorders. Importantly, metformin may have utility in the treatment of mood disorders, warranting future randomized controlled trials to test its efficacy.
Publisher: SAGE Publications
Date: 2008
DOI: 10.1080/00048670802345516
Abstract: Objective: The aim of the present study was to investigate the relationship between reduced serum vitamin D levels and psychiatric illness. Method: This study was an audit of serum 25-hydroxyvitamin D (25-OHD) levels measured routinely in a s le of 53 inpatients in a private psychiatric clinic. These levels were compared with those of controls without psychiatric illness. Results: The median levels of serum 25-OHD were 43.0 nmol L −1 (range 20–102 nmol L −1 ) in the patient population, 46.0 nmol L −1 (range 20–102 nmol L −1 ) in female patients (n =33) and 41.5 nmol L −1 (range 22–97 nmol L −1 ) in male patients (n =20). The proportion of vitamin D insufficiency (serum 25-OHD ≤50 nmol L −1 ) in this patient population was 58%. Furthermore, 11% had moderate deficiency (serum 25-OHD ≤25 nmol L −1 ). There was a 29% difference between mean levels in the patient population and control s le (geometric mean age- and season-adjusted levels: 46.4 nmol L −1 (95% confidence interval (CI) =38.6–54.9 nmol L −1 ) vs 65.3 nmol L −1 (95%CI =63.2–67.4 nmol L −1 ), p .001). Conclusion: Low levels of serum 25-OHD were found in this patient population. These data add to the literature suggesting an association between vitamin D insufficiency and psychiatric illness, and suggest that routine monitoring of vitamin D levels may be of benefit given the high yield of clinically relevant findings.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.JAD.2012.03.030
Abstract: Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based s le of women. This study examined epidemiological data obtained from 498 women aged 20-50year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented. After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1-7.8, p=0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p=0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking. This study is cross-sectional, which precludes any determination regarding the direction of the relationships. These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders.
Publisher: Cambridge University Press (CUP)
Date: 10-10-2013
DOI: 10.1017/S0007114512004102
Abstract: Fish and PUFA consumption are thought to play a role in mental health however, many studies do not take into account multiple sources of PUFA. The present study analysed data from a s le of 935 randomly selected, population-based women aged 20–93 years. A validated and comprehensive dietary questionnaire ascertained the consumption of n -3 and n -6 PUFA. Another assessed fish and energy intake and provided data for a dietary quality score. The General Health Questionnaire-12 (GHQ-12) measured psychological symptoms and a clinical interview (Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition) assessed depressive and anxiety disorders. Median dietary intakes of long-chain n -3 fatty acids (310 mg/d) were below suggested dietary target levels. The only PUFA related to categorical depressive and anxiety disorders was DHA. There was a non-linear relationship between DHA intake and depression those in the second tertile of DHA intake were nearly 70 % less likely to report a current depressive disorder compared to those in the first tertile. The relationship of DHA to anxiety disorders was linear for those in the highest tertile of DHA intake, the odds for anxiety disorders were reduced by nearly 50 % after adjustments, including adjustment for diet quality scores, compared to the lowest tertile. Those who ate fish less than once per week had higher GHQ-12 scores, and this relationship was particularly obvious in smokers. These are the first observational data to indicate a role for DHA in anxiety disorders, but suggest that the relationship between DHA and depressive disorders may be non-linear.
Publisher: Springer Science and Business Media LLC
Date: 22-02-2022
DOI: 10.1038/S41380-022-01456-3
Abstract: The emerging understanding of gut microbiota as ‘metabolic machinery’ influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to ‘healthy’ controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α- ersity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β- ersity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S12877-021-02602-2
Abstract: Poor social health is associated with increased risk of cardiovascular disease (CVD). Recent research suggests that different social health domains should be considered separately as the implications for health and possible interventions may differ. To assess social isolation, low social support and loneliness as predictors of CVD. Secondary analysis of 11,486 community-dwelling, Australians, aged 70 years and over, free of CVD, dementia, or significant physical disability, from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Social isolation, social support (Revised Lubben Social Network Scale), and loneliness were assessed as predictors of CVD using Cox proportional-hazard regression. CVD events included fatal CVD, heart failure hospitalization, myocardial infarction and stroke. Analyses were adjusted for established CVD risk factors. In iduals with poor social health were 42 % more likely to develop CVD (p = 0.01) and twice as likely to die from CVD (p = 0.02) over a median 4.5 years follow-up. Interaction effects indicated that poorer social health more strongly predicted CVD in smokers (HR 4.83, p = 0.001, p-interaction = 0.01), major city dwellers (HR 1.94, p 0.001, p-interaction=0.03), and younger older adults (70-75 years HR 2.12, p 0.001, p-interaction = 0.01). Social isolation (HR 1.66, p = 0.04) and low social support (HR 2.05, p = 0.002), but not loneliness (HR 1.4, p = 0.1), predicted incident CVD. All measures of poor social health predicted ischemic stroke (HR 1.73 to 3.16). Among healthy older adults, social isolation and low social support may be more important than loneliness as cardiovascular risk factors. Social health domains should be considered in future CVD risk prediction models.
Publisher: American Medical Association (AMA)
Date: 07-2017
Publisher: Springer Science and Business Media LLC
Date: 27-11-2012
DOI: 10.1038/TP.2012.115
Publisher: SAGE Publications
Date: 28-07-2017
Abstract: It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. Meta-analysis of published literature. PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.
Publisher: Public Library of Science (PLoS)
Date: 19-02-2016
Publisher: Elsevier BV
Date: 03-2018
Publisher: Elsevier BV
Date: 06-2016
Publisher: Cambridge University Press (CUP)
Date: 04-2011
Publisher: Cambridge University Press (CUP)
Date: 25-07-2023
DOI: 10.1017/S0033291723001733
Abstract: Family members of people with mental illness (MI) may experience a host of psychological adversities such as increased stress, burden, and reduced wellbeing. However, relatively little is known about siblings. This study aimed to characterise the experience of distress (viz. depressive and anxiety symptoms), burden, and wellbeing in siblings of people with MI. Studies reporting on quantitative measures of depression, anxiety, burden, or wellbeing in siblings and/or qualitative findings on siblings’ experience were eligible. The literature search was conducted up until 20th October 2022. Sixty-two studies comprising data from 3744 siblings were included. The pooled mean percentage of depressive symptoms fell in the mild range at 15.71 ( k = 28, N = 2187, 95% CI 12.99–18.43) and anxiety symptoms fell in the minimal range at 22.45 ( k = 16, N = 1122, 95% CI 17.09–27.80). Moderator analyses indicate that siblings of people with a schizophrenia spectrum disorder experience greater depressive symptoms than siblings of people with other types of MI ( β = −16.38, p 0.001). Qualitative findings suggest that in iduals may be particularly vulnerable during their siblings’ illness onset and times of relapse. Limited communication, confusion about MI, and the need to compensate may contribute to siblings’ distress and/or burden. Siblings’ experience of wellbeing and caregiving were closely related. This review highlights the complex psychological experience of siblings and the need for greater research and clinical support for this important yet often overlooked cohort.
Publisher: Elsevier BV
Date: 06-2013
Abstract: To investigate the relationship between socioeconomic status (SES) and reported perceptions of quality of life (QOL) in a cross-sectional population-based analysis of a representative s le of Australian men. In 917 randomly recruited men aged 24-92 years, we measured QoL in the domains of physical health, psychological health, environment and social relationships, using the Australian World Health Organization Quality of Life Instrument (WHOQOL-BREF). Residential addresses were cross-referenced with Australian Bureau of Statistics 2006 census data to ascertain SES. Participants were categorised into lower, mid, or upper SES based on the Index of Relative Socioeconomic Disadvantage and Advantage (IRSAD), the Index of Economic Resources (IER), and the Index of Education and Occupation (IEO). Lifestyle and health information was self-reported. Males of lower SES reported poorer satisfaction with physical health (OR=0.6, 95%CI 0.4-0.9, p=0.02), psychological health (OR=0.4, 95%CI 0.3-0.7, p<0.001) and environment (OR=0.5, 95%CI 0.3-0.7, p<0.001), although not social relationships (p=0.59). The poorest QOL for each domain was observed in the lower and upper SES groups, representing an inverse U-shaped pattern of association however, statistical significance was only observed for psychological health (OR=0.5, 95%CI 0.4-0.7, p<0.001). These relationships were similar for IEO and IER. Men from lower and upper SES groups have lower QOL compared to their counterparts in the mid SES group.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JAD.2017.05.030
Abstract: Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania. We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs' Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders. The social adjustment component of the PAS correlated with the interpersonal relations (r Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes. Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
DOI: 10.1007/S00213-019-05358-1
Abstract: Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one-carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe's efficacy. To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14-25) who were not currently taking antidepressants. One-carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one-carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = - 0.57, p = 0.026). The treatment was safe and well tolerated. Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. ANZCTR-Australian New Zealand Clinical Trials Registry No.: ACTRN12613001299796 URL: www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.NEULET.2011.05.027
Abstract: Oxidative stress and reduced brain levels of glutathione have been implicated in schizophrenia and bipolar disorder. N-acetyl cysteine (NAC) is a precursor of glutathione and has additional effects on glutamate neurotransmission, neurogenesis and inflammation. While NAC treatment has shown benefits in both schizophrenia and bipolar disorder, the mechanisms of action are largely unknown. Similarly, the interaction between oxidative stress and altered dopaminergic activities in psychiatric illness is not yet characterized. This study investigated the capacity of NAC in restoring brain glutathione depletion in rats that received 2-cyclohexene-1-one (CHX, 75 mg/kg), d- hetamine (2.5mg/kg) or both. CHX, but not hetamine, induced significant depletion of glutathione levels in the striatum and frontal cortex. Glutathione depletion was reversed by NAC (1000 mg/kg) in saline-treated and hetamine-treated (frontal cortex only) rats. While NAC was shown to be beneficial in this model, the lack of additional glutathione depletion by hetamine in combination with CHX does not support a summative interaction between oxidative stress and altered dopamine transmission.
Publisher: Wiley
Date: 18-02-2018
DOI: 10.1111/ACPS.12862
Abstract: This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06 I Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.
Publisher: Cambridge University Press (CUP)
Date: 17-07-2018
Publisher: Wiley
Date: 05-05-2014
DOI: 10.1111/BDI.12205
Abstract: There are no established tools to identify in iduals at risk for developing bipolar disorder. We developed a set of ultra-high-risk criteria for bipolar disorder [bipolar at-risk (BAR)]. The primary aim of the present study was to determine the predictive validity of the BAR criteria. This was a 12-month prospective study that was conducted at Orygen Youth Health Clinical Program, a public mental health program for young people aged 15-24 years in metropolitan Melbourne, Australia. At intake, BAR screen-positive in iduals and a matched group of in iduals who did not meet BAR criteria were observed over a period of 12 months. The BAR criteria include general criteria such as being in the peak age range for the onset of the disorder, as well as sub-threshold mania, depression plus cyclothymic features, and depression plus genetic risk. Conversion to first-episode mania/hypomania was defined by the presence of DSM-IV manic symptoms for more than four days, in line with the DSM-IV definition of hypomania/mania. A total of 559 help-seeking patients were screened. Of the eligible participants, 59 (10.6%) met BAR criteria. Thirty-five participants were included in the BAR group and 35 matched participants were selected to be in the control group. During the follow-up, five BAR patients out of 35 (14.3%) converted to first-episode hypomania/mania as opposed to none in the non-BAR group [χ(2) (1) = 5.38, p = 0.020]. Four out of these five converters had a DSM-IV diagnosis of bipolar I or bipolar II disorder. These findings support the possibility of identification of persons prior to the onset of mania/hypomania. The proposed criteria need further evaluation in larger, prospective studies with longer follow-up periods.
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: SAGE Publications
Date: 12-07-2023
DOI: 10.1177/10398562231189437
Abstract: Person-centred growth-oriented language and care are considered vital for achieving favourable outcomes in mental health care. Personal testimonies detailed in the Final Report of the Royal Commission into Victoria’s Mental Health System (RCVMHS) illustrate the need for a more compassionate and hope filled system, and demonstrate the opportunity to achieve this through embedding best practice person-centred growth-oriented language. A current gap exists in understanding the process and language involved in in iduals growing to mental health. Recovery has long been the paradigm for people in the mental health system ‘returning to baseline’, a stark contrast to our lived experience. We experienced a new beginning post decline, daily personal growth and healing, aiming for constant improvement as we work towards mental health, a status that many may not have even experienced before becoming unwell. Person-centred growth-oriented care includes healing, supportive relationships with the ‘caregivers’ ideally being transformation specialists knowing and understanding the process of daily personal growth. While the system is metamorphosing, it is highly recommended to embed person-centred growth-oriented language and care to aid in the transformation of in iduals in the service.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.COMPPSYCH.2009.12.001
Abstract: Tobacco smoking is more prevalent among people with mental illnesses, including bipolar disorder, than in the general community. Most data are cross-sectional, and there are no prospective trials examining the relationship of smoking to outcome in bipolar disorder. The impact of tobacco smoking on mental health outcomes was investigated in a 24-month, naturalistic, longitudinal study of 240 people with bipolar disorder or schizoaffective disorder. Participants were interviewed and data recorded by trained study clinicians at 9 interviews during the study period. Comparisons were made between participants who smoked daily (n = 122) and the remaining study participants (n = 117). During the 24-month study period, the daily smokers had poorer scores on the Clinical Global Impressions-Depression (P = .034) and Clinical Global Impressions-Overall Bipolar (P = .026) scales and had lengthier stays in hospital (P = .012), compared with nonsmokers. Smoking status was determined by self-report. Nicotine dependence was not measured. These findings suggest that smoking is associated with poorer mental health outcomes in bipolar and schizoaffective disorder.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.JAD.2007.06.011
Abstract: Current definitions of remission for mania and bipolar depression are convention-rather than empirically-based, and their clinical salience is unclear, as few studies have attempted to calibrate them against objective clinical criteria. This study aimed to determine equivalence scores on two widely used clinical rating scales, the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS), that corresponded with an objective global clinical measure of remission in bipolar disorder patients. Data from four pharmacological randomised controlled trials in bipolar I disorder were analysed. Two trials were conducted for bipolar depression (N=410 and 833), and two for manic or mixed episodes (N=136 and 110). In this study, a Clinical Global Impression-Bipolar Version (CGI-BP) severity score of 1 (normal, not at all ill) was used as the primary comparative measure of remission. The mean total YMRS and MADRS scores in the mania and depression studies, respectively, that corresponded with a CGI-BP severity score of 1 were determined. The mean YMRS score that corresponded with a CGI-BP severity score of 1 was <4 in both trials (2.6 and 3.0, respectively), and the mean corresponding MADRS score was <5 (4.1 and 4.6, respectively). Utilising a psychometric definition of remission. This study suggests that a cut-off score of <5 on the MADRS and <4 on the YMRS approximates a CGI-BP definition of complete remission. Although lower than conventional cut-off scores, these perhaps better represent clinical reality and patient expectations. In the context of clinical trials, study end-points may be more difficult to reach with lower cut-offs, but the outcomes achieved are more likely to be clinically meaningful.
Publisher: Wiley
Date: 10-2012
DOI: 10.1111/J.1440-1819.2012.02392.X
Abstract: Bipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic in iduals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment. As part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000 mg of NAC daily or placebo. This study failed to find changes in cognitive function following treatment with NAC compared to placebo. While an important pilot study, this study had a small s le size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2018
Publisher: SAGE Publications
Date: 04-2013
Publisher: JMIR Publications Inc.
Date: 07-04-2022
DOI: 10.2196/17180
Abstract: Improved understanding of social constructs around injury may help insurance case managers to understand how best to support people after injury. This study sought to explore what people who sustain work-related injuries may seek from online communities. The study highlights potential opportunities for improved engagement with insurance case management practice. An observational netnographic analysis was undertaken on anonymous, publicly available messages posted on Australian message boards. All research data were drawn from anonymous, online communities. A person (author SM) with experience of making a claim through an Australian workers’ compensation system and online engagement was involved in study conception, design, and analysis. Data were analyzed using NVivo12 in an iterative, multistage process including coding, journaling, and member checking. A total of 141 people were engaged in discussion across 47 threads housed on 4 Australian forums. In this qualitative study, themes emerged from the data, describing how injured workers use online communities to help make decisions, get support, and solve problems. The key motivators for action and engagement were seeking information, connection, or justice. Establishment of relationships was a key mediator of each of these parameters. Some work-related injuries may involve medical and medicolegal complexity as well as changed lifestyle and routine during convalescence and recovery. The mechanism used by some injured workers to seek information and problem solve suggests a capacity for self-management and self-care after work-related injury. Netnography provides information on a community that may not regularly engage with research because of the complexity of their situation and their vulnerability.
Publisher: SAGE Publications
Date: 10-05-2016
Abstract: Socioeconomic trends herald what many describe as the Asian Century, whereby Asian economic, political and cultural influence is in global ascendency. Broadening relevant ties between Australia and Asia is evident and logical and may include strengthening alliances in mental health systems. We argue the importance of strengthening Asian mental health systems and some of the roles Australian mental health workers could have in promoting strengthening the Asian mental health system. This paper is a narrative review which sources data from reputable search databases. A well-articulated Australian strategy to support strengthening the mental health system in Asia is lacking. While there are active initiatives operating in this space, these remain fragmented and underdeveloped. Coordinated, collaborative and culturally respectful efforts to enhance health education, research, policy, leadership and development assistance are key opportunities. Psychiatrists and other mental health professionals have a unique opportunity to contribute to improved mental health outcomes in Asia.
Publisher: Elsevier BV
Date: 02-2201
Publisher: SAGE Publications
Date: 11-01-2023
DOI: 10.1177/00048674221144262
Abstract: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants ( N = 283) were 15–25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.
Publisher: MDPI AG
Date: 28-05-2019
DOI: 10.3390/NU11061196
Abstract: Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-035080
Abstract: Due to the anti-inflammatory, antioxidant and anti-apoptotic properties of minocycline, clinical trials have evaluated the potential of this drug to treat several psychiatric and neurological disorders, including major depressive disorder, schizophrenia, bipolar disorder, stroke and amyotrophic lateral sclerosis. This protocol proposes a systematic review (and potential meta-analysis) that aims to identify and critically evaluate randomised controlled trials of minocycline for treating psychiatric and neurological disorders. PubMed, Embase, Cochrane Central Register of Controlled Clinical Trials, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be used to identify randomised controlled trials that used minocycline to treat psychiatric and neurological disorders. Double-blind, randomised, controlled, clinical trials of participants aged 18 years or older and written in English will be included in the review. Data will be extracted by two independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed and the Cochrane Collaboration’s ‘Risk of Bias’ tool will be used to assess the risk of bias in all studies included in the systematic review. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to access the overall quality of the level of evidence of the studies. If sufficient evidence is identified, a meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. Heterogeneity of evidence will be evaluated using the I 2 model. This systematic review will evaluate only published data therefore, ethical approval is not required. The systematic review will be published in a peer-reviewed journal and presented at relevant research conferences. CRD42020153292.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.EURONEURO.2022.09.002
Abstract: Advances in psychopharmacology have been significantly slower to evolve than in other disciplines of medicine and therefore investigation into novel therapeutic approaches is required. Additionally, concurrent metabolic conditions are prevalent among people with mental disorders. Metformin is a widely used hypoglycaemic agent that is now being studied for use beyond diabetes management. Evidence is emerging that metformin has multiple effects on erse neurobiological pathways and consequently may be repurposed for treating mental illness. Metformin may have beneficial neuroimmunological, neuroplastic, neuro-oxidative and neuro-nitrosative effects across a range of psychiatric and neurodegenerative illnesses. Mechanisms include glucose lowering effects and effects on AMP-activated protein kinase (AMPK) signalling, however the best evidence for clinical benefit is through the glucose lowering effects, with other mechanisms less supported by the current evidence base. This narrative review aims to draw together the existing evidence for use of metformin as a psychopharmaceutical and present the role of metformin in the context of physical and psychiatric ill health, including metabolic, endocrinological and cancer domains. It not only has therapeutic potential in medical comorbidity but may have potential in core illness domains.
Publisher: Cold Spring Harbor Laboratory
Date: 15-02-2022
DOI: 10.1101/2022.02.11.22270818
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP age of onset years). However, as neuroimaging methods vary and s le sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls (CTR) using diffusion tensor imaging (DTI). Our s le included 321 adolescents with EOP (mean age: 16.3 ± 1.4 years, 46.4% females) and 265 adolescent CTR (mean age: 16.0 ± 1.7 years, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to CTR, with the largest effect sizes in the superior longitudinal fasciculus (Cohen’s d = 0.37), posterior corona radiata ( d = 0.32), and superior fronto□occipital fasciculus ( d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI s le to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male patients with early-onset schizophrenia and patients with a shorter duration of illness.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 05-2007
Publisher: Elsevier BV
Date: 09-2019
Publisher: Wiley
Date: 03-12-2023
DOI: 10.1002/GPS.5847
Abstract: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. We used data from the D‐Health Trial ( N = 21,315), a randomized double‐blind placebo‐controlled trial of monthly vitamin D 3 for the prevention of all‐cause mortality. Participants were Australians aged 60–84 years. Participants completed the Patient Health Questionnaire (PHQ–9) at 1, 2 and 5 years after randomization to measure depressive symptoms national prescribing records were used to capture antidepressant use. We used mixed models and survival models. Analyses of PHQ‐9 scores included 20,487 participants (mean age 69·3 years, 46% women) the mean difference (MD) in PHQ‐9 score (vitamin D vs. placebo) was 0·02 (95% CI −0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ‐9 score ≥10) (odds ratio 0·99 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ‐9 scores in those taking antidepressants at baseline (MD −0·25 95% CI −0·49, −0·01 p‐interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration nmol/L (HR 0·88 95% CI 0·75, 1·02 p‐interaction = 0·01) and increased risk in those with predicted 25(OH) D ≥ 50 nmol/L (HR 1·10 95% CI 1·01, 1·20). Monthly supplementation with high‐dose vitamin D 3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses. The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. www.anzctr.org.au/ .
Publisher: Oxford University Press (OUP)
Date: 02-02-2016
DOI: 10.1093/IJNP/PYW008
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 03-12-2022
DOI: 10.1111/ADD.16085
Abstract: Treatment of meth hetamine dependence requires monitoring of recent use or abstinence. Self‐report is commonly used for routine monitoring, but the accuracy of self‐report is not established. For the treating clinician, the key accuracy statistic is the negative predictive value (NPV). The study aim was to estimate the NPV of self‐reported non‐use of meth hetamine compared with an oral fluid reference standard. This study was a secondary (subgroup) analysis from a randomized controlled pharmacotherapy trial. Three Australian outpatient addiction services took part. Particpants were 139 people dependent on meth hetamine. Weekly oral fluid s les over 12 weeks to determine meth hetamine (and hetamine) concentrations were used as the reference standard. Self‐report of any meth hetamine use in the previous 7 days by the time‐line follow‐back method was the index test. Standard diagnostic accuracy statistics were calculated for all available paired episodes ( n = 1134). Three NPV values were calculated: unadjusted NPV and NPV adjusted for clustering of observations through logistic regression and generalized estimating equation (GEE). We also calculated the NPVs for a range of prevalence rates of meth hetamine use, for the calculated levels of sensitivity and specificity. Sensitivity was 96.4% [95% confidence interval (CI) = 95–97.5], specificity was 63.7% (95% CI = 57.3–69.8) and positive predictive value (PPV) was 90.8% (95% CI = 88.8–92.6). The unadjusted NPV was 82.7% (95% CI = 76.5–87.9), adjusted NPV by logistic regression 82.7% (95% CI = 73.9–91.5) and GEE 76.8% (95% CI = 66.8–86.8). At a meth hetamine use prevalence of 5%, the estimated NPV would be 99.7% (95% CI = 99.6–99.9) and at 95% prevalence, 48.2% (95% CI = 39.6–57.0). Self‐report of no recent meth hetamine use appears to be sufficiently accurate to be clinically useful at the expected prevalence rates of meth hetamine use in clinical treatment settings. If generalizable to clinical settings, where these tests are routinely conducted, this may permit a reduction in the frequency and cost of oral fluid assays.
Publisher: BMJ
Date: 18-07-2014
Publisher: Elsevier BV
Date: 2020
Publisher: SAGE Publications
Date: 26-05-2023
Publisher: Springer Science and Business Media LLC
Date: 19-10-2023
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.MSARD.2019.101486
Abstract: Due to the considerable burden of multiple sclerosis (MS)-related symptoms and the need to identify effective interventions to prevent disease progression, various nutraceutical interventions have been trialed as adjunctive treatments. The aim of this review was to investigate the efficacy and safety of nutraceutical interventions for clinical and biological outcomes in people with MS. In accordance with PRISMA reporting guidelines, a systematic literature search was conducted using three electronic literature databases. Risk of bias was assessed using the Jadad scale. Thirty-seven randomized controlled trials, investigating fourteen nutraceuticals, were included in the review. Trials that investigated alpha lipoic acid (n = 4/6), ginkgo biloba (n = 3/5), vitamin A (n = 2/2), biotin (n = 1/2), carnitine (n = 1/2), green tea (n = 1/2), coenzyme Q10 (n = 1/1), probiotics (n = 1/1), curcumin (n = 1/1), Andrographis paniculata (n = 1/1), ginseng (n = 1/1), and lemon verbena (n = 1/1) were reported to improve biological (e.g. MRI brain volume change, antioxidant capacity) and/or clinical (e.g. fatigue, depression, Expanded Disability Status Scale) outcomes in multiple sclerosis compared to control. However, most trials were relatively small (average study s le size across included studies, n = 55) and there were few replicate studies per nutraceutical to validate the reported results. Furthermore, some nutraceuticals (e.g. green tea and inosine) should be used with caution due to reported adverse events. Risk of bias across most studies was low, with 31 studies receiving a score between 4 and 5 (out of 5) on the Jadad Scale. The existing literature provides preliminary support for the use of a number of nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as the gut microbiome and mitochondrial dysfunction. Prospero ID: CRD42018111736.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.NEUBIOREV.2019.09.025
Abstract: Activated immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways and consequent mitochondrial aberrations are involved in the pathophysiology of psychiatric disorders including major depression, bipolar disorder and schizophrenia. They offer independent and shared contributions to pathways underpinning medical comorbidities including insulin resistance, metabolic syndrome, obesity and cardiovascular disease - herein conceptualized as somatoprogression. This narrative review of human studies aims to summarize relationships between IO&NS pathways, neuroprogression and somatoprogression. Activated IO&NS pathways, implicated in the neuroprogression of psychiatric disorders, affect the pathogenesis of comorbidities including insulin resistance, dyslipidaemia, obesity and hypertension, and by inference, metabolic syndrome. These conditions activate IO&NS pathways, exacerbating neuroprogression in psychiatric disorders. The processes whereby proinflammatory cytokines, nitrosative and endoplasmic reticulum stress, NADPH oxidase isoforms, PPARγ inactivation, SIRT1 deficiency and intracellular signalling pathways impact lipid metabolism and storage are considered. Through associations between body mass index, chronic neuroinflammation and FTO expression, activation of IO&NS pathways arising from somatoprogression may contribute to neuroprogression. Early evidence highlights the potential of adjuvants targeting IO&NS pathways for treating somatoprogression and neuroprogression.
Publisher: Portico
Date: 09-2003
DOI: 10.1023/B:ACLI.0000008175.32403.8E
Abstract: Adverse events associated with lithium and anticonvulsant use in patients with bipolar disorder have been determined to decrease rates of treatment adherence however, research that explores how adverse events influence treatment adherence, and which events have the greatest impact, is sparse and limited. This paper reviews the existing literature regarding common side effects encountered with lithium and anticonvulsant use in patients with bipolar disorder and presents data regarding their impact on treatment adherence. Guidelines for reducing and limiting adverse events are highlighted, as are recommendations for improving compliance associated with the experience of adverse events in the bipolar disorder population.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.PSCYCHRESNS.2011.06.010
Abstract: There are now numerous reports of neuroanatomical abnormalities in people with bipolar disorder. However, it remains unclear whether those abnormalities predate the onset of the illness. In this cross-sectional magnetic resonance imaging study, we assessed 11 young people clinically at ultra-high risk of development of psychosis (UHR), who all developed bipolar I or II disorder by follow-up (median time to onset 328 days - UHR-BP), 11 matched UHR participants, who had no psychiatric diagnosis after at least 12 months of follow-up (UHR-Well) and 11 matched healthy controls (HC). Our main outcome measures were amygdala, hippoc us, insula, lateral ventricular and whole brain volumes. Amygdala and insula volume reductions were more pronounced in the UHR-BP than in the UHR-Well and HC group. Lateral ventricle, whole-brain and hippoc al volumes did not differ between groups. If these findings are confirmed, they suggest that imaging investigations could help to distinguish people who will subsequently develop bipolar disorder from those who will not, at least in symptomatically enriched s les.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.JAD.2008.08.011
Abstract: In the absence of clear targets for primary prevention of many psychiatric illnesses, secondary prevention becomes the most feasible therapeutic target, and is best encompassed by the concept of early intervention. This construct encompasses the goals of minimising diagnostic delay and the prompt initiation of clinically appropriate therapy. This paper develops the rationale for early intervention in bipolar disorder. Three interrelated themes are discussed the clinical data supporting the value of prompt diagnosis and treatment in bipolar disorder, the putative biochemical mechanisms underlying the pathophysiological processes, and the parallel concept of neuroprotection, and the developing neuroimaging data that supports early intervention. Early initiation of appropriate therapy may potentially facilitate improved clinical outcomes, and further might allow the secondary prevention of the sequelae of untreated illness, which include the deleterious impact on family relationships, psychosexual and vocational development, identity and self-concept and self-stigma.
Publisher: EDITORA SCIENTIFIC
Date: 07-10-2015
DOI: 10.1590/1516-4446-2013-1341
Abstract: Bipolar disorder places a significant burden on in iduals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood s les will be collected at baseline and week 16 to explore biochemical alterations following treatment. This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological s les may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.
Publisher: African Journals Online (AJOL)
Date: 23-07-2013
Publisher: Mary Ann Liebert Inc
Date: 09-2005
Abstract: Psychiatric illness, mostly mania and psychosis, are reported to occur after rapid normalization of thyroid function in patients with primary hypothyroidism. It is generally believed that the gradual restoration of thyroid function may reduce the risk of psychiatric complications. This case report describes the occurrence of acute delirium in a 67-year-old man with primary hypothyroidism shortly after the initiation of thyroid hormone replacement. The use of low-dose thyroxine initially and persistent severe biochemical hypothyroidism on presentation with psychiatric symptoms illustrate that psychiatric illness can still occur despite unaggressive thyroid hormone replacement. A temporal relationship with the initiation of thyroxine and rapid recovery of mental state over 1 to 2 weeks differentiate this condition from hypothyroidism-related psychopathology, which tends to have a more prolonged course.
Publisher: Springer Science and Business Media LLC
Date: 07-04-2017
Publisher: Informa UK Limited
Date: 05-07-2021
Publisher: Springer Science and Business Media LLC
Date: 06-08-2020
DOI: 10.1186/S12888-020-02793-9
Abstract: Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain’s primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger s le in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD. A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2. This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC. ACTRN12618001784202, retrospectively registered 31/10/2018, URL: www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004 .
Publisher: Springer Science and Business Media LLC
Date: 24-04-2013
Abstract: The mind-body nexus has been a topic of growing interest. Further data are however required to understand the specific relationship between mood and anxiety disorders and in idual physical health conditions, and to verify whether these psychiatric disorders are linked to overall medical burden. This study examined data collected from 942 men, 20 to 97 years old, participating in the Geelong Osteoporosis Study. A lifetime history of mood and anxiety disorders was identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). The presence of medical conditions (lifetime) was self-reported and confirmed by medical records, medication use or clinical data. Anthropometric measurements and socioeconomic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Logistic regression models were used to test the associations. After adjustment for age, socioeconomic status, and health risk factors (body mass index, physical activity and smoking), mood disorders were associated with gastro oesophageal reflux disease (GORD), recurrent headaches, blackouts and/or epilepsy, liver disorders and pulmonary disease in older people, whilst anxiety disorders were significantly associated with thyroid, GORD and other gastrointestinal disorders, and psoriasis. Increased odds of high medical burden were associated with both mood and anxiety disorders. Our study provides further population-based evidence supporting the link between mental and physical illness in men. Understanding these associations is not only necessary for in idual management, but also to inform the delivery of health promotion messages and health care.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.JAD.2012.09.025
Abstract: The common mental disorders are potential risk factors for low bone mass as a result of disease and/or medication-related processes. Quantitative heel ultrasound (QUS) is a portable and relatively cheap screening tool for determining fracture risk. Thus, we investigated the association between QUS parameters, mood and anxiety disorders in a population-based s le of 745 men and 897 women. Using a clinical interview (SCID-I/NP), mood and anxiety disorders were identified. Bone quality was established using QUS and included the following parameters: Broadband Ultrasound Attenuation (BUA), Speed of Sound (SOS) and Stiffness Index (SI). Anthropometry, socio-economic status (SES), medication use and lifestyle factors were determined. In men, mood and anxiety disorders were associated with lower age-weight- and smoking-adjusted SOS, BUA and SI. In women, age was an effect modifier. Among younger women (≤ 40yr), mood disorders were associated with lower age-weight- and smoking-adjusted SOS and SI but not BUA. No differences were detected in older women or women with anxiety disorders. These patterns persisted after adjustment for activity, alcohol, calcium intake, SES and medications. Cross-sectional study design, and possible residual or unrecognised confounding. Our data suggest that bone quality, as measured by QUS, is reduced among men and younger women with a history of mood disorders. Furthermore, an inverse association between anxiety disorders and bone quality was evident for men. Thus, QUS may be a useful screening tool for determining fracture risk within these populations.
Publisher: Informa UK Limited
Date: 04-2010
DOI: 10.3109/09638230903469111
Abstract: To review the evidence that supports early intervention in the treatment of bipolar disorder. Bipolar disorder is a pleomorphic condition, with varying manifestations that are determined by a number of complex factors including the "stage" of illness. It is consequently a notoriously difficult illness to diagnose and as a corollary is associated with lengthy delays in recognition and the initiation of suitable treatment. A literature search was conducted using MEDLINE augmented by a manual search. Emerging neuroimaging data suggests that, in contrast to schizophrenia, where at the time of a first-episode of illness there is already discernible volume loss, in bipolar disorder, gross brain structure is relatively preserved, and it is only with recurrences that there is a sequential, but marked loss of brain volume. Recent evidence suggests that both pharmacotherapy and psychotherapy are more effective if instituted early in the course of bipolar disorder, and that with multiple episodes and disease progression there is a noticeable decline in treatment response. Such data supports the notion of clinical staging, and the tailored implementation of treatments according to the stage of illness. The progressive nature of bipolar disorder further supports the concept that the first episode is a period that requires energetic broad-based treatment, with the hope that this could alter the temporal trajectory of the illness. It also raises hope that prompt treatment may be neuroprotective and that this perhaps attenuates or even prevents the neurostructural and neurocognitive changes seen to emerge with chronicity. This highlights the need for early identification at a population level and the necessity of implementing treatments and services at a stage of the illness where prognosis is optimal.
Publisher: Springer Science and Business Media LLC
Date: 19-10-2020
DOI: 10.1186/S12916-020-01749-W
Abstract: Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB platelet activation atherogenic miRs myeloperoxidase xanthene oxidase and uric acid and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.
Publisher: Wiley
Date: 18-01-2017
DOI: 10.1111/ACPS.12686
Abstract: Some people with major depressive disorder (MDD) may be at a pre-onset stage for bipolar disorder (BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow-up studies of people with MDD. Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow-up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios (OR) for baseline predictors. From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12-18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta-analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01-4.14, N = 7), earlier age of onset of depression (g = -0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79-12.66, N = 5). Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered.
Publisher: SAGE Publications
Date: 08-04-2022
Publisher: Frontiers Media SA
Date: 06-07-2021
DOI: 10.3389/FPHAR.2021.705254
Abstract: For over 40 years, in vivo microdialysis techniques have been at the forefront in measuring the effects of illicit substances on brain tonic extracellular levels of dopamine that underlie many aspects of drug addiction. However, the size of microdialysis probes and s ling rate may limit this technique’s ability to provide an accurate assessment of drug effects in microneural environments. A novel electrochemical method known as multiple-cyclic square wave voltammetry (M-CSWV), was recently developed to measure second-to-second changes in tonic dopamine levels at microelectrodes, providing spatiotemporal resolution superior to microdialysis. Here, we utilized M-CSWV and fast-scan cyclic voltammetry (FSCV) to measure changes in tonic or phasic dopamine release in the nucleus accumbens core (NAcc) after acute cocaine administration. Carbon-fiber microelectrodes (CFM) and stimulating electrodes were implanted into the NAcc and medial forebrain bundle (MFB) of urethane anesthetized (1.5 g/kg i.p.) Sprague-Dawley rats, respectively. Using FSCV, depths of each electrode were optimized by determining maximal MFB electrical stimulation-evoked phasic dopamine release. Changes in phasic responses were measured after a single dose of intravenous saline or cocaine hydrochloride (3 mg/kg n = 4). In a separate group, changes in tonic dopamine levels were measured using M-CSWV after intravenous saline and after cocaine hydrochloride (3 mg/kg n = 5). Both the phasic and tonic dopamine responses in the NAcc were augmented by the injection of cocaine compared to saline control. The phasic and tonic levels changed by approximately x2.4 and x1.9, respectively. These increases were largely consistent with previous studies using FSCV and microdialysis. However, the minimal disruption/disturbance of neuronal tissue by the CFM may explain why the baseline tonic dopamine values (134 ± 32 nM) measured by M-CSWV were found to be 10-fold higher when compared to conventional microdialysis. In this study, we demonstrated phasic dopamine dynamics in the NAcc with acute cocaine administration. M-CSWV was able to record rapid changes in tonic levels of dopamine, which cannot be achieved with other current voltammetric techniques. Taken together, M-CSWV has the potential to provide an unprecedented level of physiologic insight into dopamine signaling, both in vitro and in vivo , which will significantly enhance our understanding of neurochemical mechanisms underlying psychiatric conditions.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JAD.2013.05.016
Abstract: There is evidence that depression is accompanied by inflammation, oxidative and nitrosative stress (O&NS) and metabolic disorders. However links between oxidative stress and suicide attempts in depressed patients are poorly understood. This study examines whether a history of suicide attempts is associated with inflammation, O&NS and metabolic disorders. Blood specimens were collected from study participants aged 18-60 (N=342) recruited at the State University of Londrina, Brazil, and measured for oxidative stress biomarkers: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde, advanced oxidation protein products and plasma total antioxidant potential (TRAP) inflammatory biomarkers: fibrinogen, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, interleukin-6 and tumor necrosis factor-α and metabolic variables. Subjects were ided into those with (n=141) and without (n=201) a history of suicidal attempts. In iduals with a history of suicide attempts had significantly higher levels of NOx and lipid hydroperoxides and lowered TRAP as compared to in iduals without suicide attempts. There were no significant associations between a history of suicide attempts and inflammatory and metabolic biomarkers and metabolic syndrome. Logistic regression showed that both unipolar and bipolar disorder, female gender, smoking behavior and lipid hydroperoxides were significantly associated with a history of suicide attempts. The combined effects of oxidative stress, smoking, depression, female gender were independent from classical risk factors, including marital status, years of education and anxiety. O&NS as well as lowered antioxidant levels may play a role in the pathophysiology of suicidal behavior independently from the effects of depression and smoking, both of which are associated with increased O&NS, and classical suicide predictors, such as years of education and marital status.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2016
DOI: 10.1038/SREP28533
Abstract: Extracellular data analysis has become a quintessential method for understanding the neurophysiological responses to stimuli. This demands stringent techniques owing to the complicated nature of the recording environment. In this paper, we highlight the challenges in extracellular multi-electrode recording and data analysis as well as the limitations pertaining to some of the currently employed methodologies. To address some of the challenges, we present a unified algorithm in the form of selective sorting. Selective sorting is modelled around hypothesized generative model, which addresses the natural phenomena of spikes triggered by an intricate neuronal population. The algorithm incorporates Cepstrum of Bispectrum, ad hoc clustering algorithms, wavelet transforms, least square and correlation concepts which strategically tailors a sequence to characterize and form distinctive clusters. Additionally, we demonstrate the influence of noise modelled wavelets to sort overlapping spikes. The algorithm is evaluated using both raw and synthesized data sets with different levels of complexity and the performances are tabulated for comparison using widely accepted qualitative and quantitative indicators.
Publisher: Springer Science and Business Media LLC
Date: 13-02-2018
DOI: 10.1007/S00223-018-0398-0
Abstract: Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based s le of men (n = 1138 20-96 year) participating in the Geelong Osteoporosis Study. Blood s les were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20-60 year n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6-18.8) vs 19.1 (95% CI 18.7-19.4) pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9-6.3) vs 6.4 (95% CI 6.3-6.6) pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61-94 year all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.
Publisher: Informa UK Limited
Date: 30-12-2010
Publisher: SLACK, Inc.
Date: 08-2023
DOI: 10.3928/00485713-20230718-01
Abstract: Experienced clinicians and academics from the International MAOI Expert Group comment on questions of interest concerning monoamine oxidase inhibitor (MAOI) pharmacotherapy for depression. These comments in this Part Two of the Expert Roundtable Discussion emphasize good pharmacological practice, starting with a low dose and progressing slowly and only changing one element at a time. Issues related to augmentation and drug combinations are also mentioned, including comments about the safety of ketamine. The special ability of MAOIs to improve dopamine function is highlighted, especially in relation to melancholic and psychotic depression. [ Psychiatr Ann . 2023 (8):364–369.]
Publisher: Korean College of Neuropsychopharmacology
Date: 30-04-2015
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.NEULET.2014.11.002
Abstract: There is evidence that genetic factors influence the probability of comorbidity of tobacco use disorder (TUD) with mood disorders. This study was carried out to examine whether both TUD and mood disorders are associated with genetic biomarkers particularly paraoxonase 1 (PON1) status, polymorphisms of glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the STIn 2 polymorphism of the serotonin transporter. PON1 status (Q192R polymorphism and PON1 plasmatic activity), GSTM1, GSTT1, and STin.2 genotypes and alleles were assayed in 4 mutually exclusive study groups, i.e., comorbid mood disorder and TUD (n=95) TUD without mood disorders (n=90) mood disorders but no TUD (n=62) and controls (never-smokers without mood disorders n=113). Logistic regression analyses showed that comorbid mood disorders and TUD were associated with significantly lower PON1 activity, the STin2.10/10 genotype (protective) or the Stin2.12 allele (risk factor) and the GSTM1 and GSTT1 null genotypes (protective). These results show that comorbid mood disorders and TUD are associated with specific biomarkers related to oxidative stress and serotonin pathways.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.JAD.2013.11.009
Abstract: Atopy, a common disorder characterized by a sensitivity to allergic reactions, affects a large proportion of the adult population and, as with depression, is associated with immune-inflammatory pathway changes. We sought to determine the role of atopic disorders in depression using data from a randomly-selected, population-based study of men and women. Cross-sectional data derived from the Geelong Osteoporosis Study for 942 males and 1085 females were analyzed. Depression [major depressive disorder (MDD), minor depression and dysthymia] was assessed using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition. Data on medical conditions, including atopic disorders (asthma, hay fever and eczema), smoking status, alcohol consumption, socioeconomic status, and physical activity were documented by self-report. Logistic regression modeling was used to explore the associations between atopic disorders and depression. Atopic disorders were associated with a 59% increased likelihood of depression [gender and smoking-adjusted odds ratio (OR) 1:50, 95% CI 1.20-1.97]. Sub-group analyses revealed a similar pattern for those with MDD [gender and smoking-adjusted OR 1:54, 95% CI 1.22-1.94]. These associations were independent of socio-demographic characteristics, clinical and lifestyle factors. Reliance on self-report for allergic symptoms and cross-sectional nature of study. This population-based study provides evidence of the potential contribution of allergic disorders to depression. Further research is required to elucidate the direction of this association and to further explicate its underlying physiology, including immune-inflammation markers.
Publisher: Wiley
Date: 05-2009
DOI: 10.1111/J.1600-0447.2009.01383.X
Abstract: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of in idual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JAD.2012.09.017
Abstract: Cognitive deficits have been well documented in in iduals with bipolar disorder (BD) after the first episode of mania. However, little is known about the presence of such deficits prior to the initial manic episode. Participants were recruited from a cohort of 416 young people who were at ultra-high risk (UHR) for psychosis and were followed up between 4 and 13 years later. The current report is of 16 participants who developed BD over a mean follow-up period of 8.2 years (UHR-BD). Baseline demographic, clinical and neurocognitive assessment scores were compared with those of 46 age and gender matched UHR subjects who did not transition to psychosis or BD over the follow-up period (UHR-NT) and 66 healthy comparison subjects. UHR-BD subjects had lower global functioning at baseline compared with UHR-NT subjects. There were no significant differences between UHR-BD and UHR-NT subjects on baseline demographic and neurocognitive characteristics. UHR-BD subjects had lower test performance than HC on picture completion, Trail-Making Tests and measures of global intelligence. Small s le size, limited and variable neurocognitive tests utilised and the confounding effects of psychotic symptoms might have impacted on the ability to detect meaningful clinical and neurocognitive differences. In this exploratory study, neurocognition in young people who later develop BD is similar to those of subjects who are at a high risk for psychotic disorders, but there may be certain neurocognitive markers that distinguish this group from unaffected and healthy young people.
Publisher: Informa UK Limited
Date: 03-2011
Publisher: Elsevier BV
Date: 2019
Publisher: Informa UK Limited
Date: 07-2013
DOI: 10.3109/15622975.2013.804195
Abstract: This 2013 update of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal has been to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. The guidelines are intended for use by all physicians seeing and treating patients with these conditions. The 2013 update was conducted by a systematic update literature search and appraisal. All recommendations were approved by the Guidelines Task Force. This first part of the guidelines (Part 1) covers disease definition, classification, epidemiology, and course of unipolar depressive disorders, as well as the management of the acute and continuation phase treatment. It is primarily concerned with the biological treatment (including antidepressants, other psychopharmacological medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of adults. To date, there is a variety of evidence-based antidepressant treatment options available. Nevertheless there is still a substantial proportion of patients not achieving full remission. In addition, somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated. Therefore, further high-quality informative randomized controlled trials are urgently needed.
Publisher: Royal College of Psychiatrists
Date: 04-2013
DOI: 10.1192/BJP.BP.112.110858
Abstract: Staging models are used routinely in general medicine for potentially serious or chronic physical disorders such as diabetes, arthritis and cancers, describing the links between biomarkers, clinical phenotypes and disease extension, and promoting a personalised or stratified medicine approach to treatment planning. Clinical staging involves a detailed description of where an in idual exists on a continuum of disorder progression from stage 0 (an at-risk or latency stage) through to stage IV (late or end-stage disease). The approach is popular owing to its clinical utility and is increasingly being applied in psychiatry. The concept offers an informed approach to research and the active promotion of indicated prevention and early intervention strategies. We suggest that for young persons with emerging bipolar disorder, such transdiagnostic staging models could provide a framework that better reflects the developmental psychopathology and matches the complex longitudinal inter-relationships between subsyndromal and syndromal mood, psychotic and other disorders.
Publisher: Cambridge University Press (CUP)
Date: 04-2010
Publisher: Elsevier BV
Date: 08-2017
Publisher: BMJ
Date: 02-2017
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.SCHRES.2021.11.048
Abstract: The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of in idual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to in iduals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 in iduals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of in idual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, in iduals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features.
Publisher: Wiley
Date: 19-09-2014
DOI: 10.1111/BDI.12258
Abstract: Self-management is emerging as a viable alternative to difficult-to-access psychosocial treatments for bipolar disorder (BD), and has particular relevance to recovery-related goals around empowerment and personal meaning. This review examines data and theory on BD self-management from a recovery-oriented perspective, with a particular focus on optimizing low-intensity delivery of self-management tools via the web. A critical evaluation of various literatures was undertaken. Literatures on recovery, online platforms, and self-management in mental health and BD are reviewed. The literature suggests that the self-management approach aligns with the recovery framework. However, studies have identified a number of potential barriers to the utilization of self-management programs for BD and it has been suggested that utilizing an online environment may be an effective way to surmount many of these barriers. Online self-management programs for BD are rapidly developing, and in parallel the recovery perspective is becoming the dominant paradigm for mental health services worldwide, so research is urgently required to assess the efficacy and safety of optimization methods such as professional and/or peer support, tailoring and the development of 'online communities'.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2019
Publisher: Cambridge University Press (CUP)
Date: 13-08-2018
DOI: 10.1017/S1041610218000856
Abstract: Both elevated blood pressure and/or depression increase the risk of cardiovascular disease and mortality. This study in treated elderly hypertensive patients explored the incidence of depression, its association (pre-existing and incident) with mortality and predictors of incident depression. Data from 6,083 hypertensive patients aged ≥65 years enrolled in the Second Australian National Blood Pressure study were used. Participants were followed for a median of 10.8 years (including 4.1 years in-trial) and classified into: “no depression,” “pre-existing” and “incident” depression groups based on either being “diagnosed with depressive disorders” and/or “treated with an anti-depressant drug” at baseline or during in-trial period. Further, we redefined “depression” restricted to presence of both conditions for sensitivity analyses. For the current study, end-points were all-cause and any cardiovascular mortality. 313 (5%) participants had pre-existing depression and a further 916 (15%) participants developed depression during the trial period (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all-cause mortality was observed among those with either pre-existing (1.23, 1.01–1.50 p = 0.03) or incident (1.26, 1.12–1.41 p 0.001) depression compared to those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05–1.47 p = 0.01) was observed among those with incident depression. The sensitivity analyses, using the restricted depression definition showed similar associations. Incident depression was associated with being female, aged ≥75 years, being an active smoker at study entry, and developing new diabetes during the study period. This elderly cohort had a high incidence of depression irrespective of their randomised antihypertensive regimen. Both pre-existing and incident depression were associated with increased mortality.
Publisher: SAGE Publications
Date: 06-05-2017
Abstract: Few population-based studies have been used to investigate secular trends in psychotropic medication use. Therefore, the aim of this study was to examine psychotropic medication use over time using data from the Geelong Osteoporosis Study, an on-going, population-based, cohort study of Australian women. Of the 1494 women recruited at Time 1 (1993–1997), self-reported medication use from Time 2 (2004–2008) and/or Time 3 (2011–2014) was available for 889 women. Prevalence of antidepressant/antipsychotic/anxiolytic/sedative/anticonvulsant use by age and cohort strata was calculated using bootstrapping methods. Simultaneous age-cohort patterns were evaluated using logistic regression techniques. The prevalence of any psychotropic medication use increased from 8.0% (95% confidence interval = [6.3, 9.8]) at Time 1 to 26.0% (95% confidence interval = [22.4, 29.4]) at Time 3, translating to a 4.3-fold increase in the likelihood of psychotropic medication use over the study period (odds ratio = 4.3, 95% confidence interval = [3.2, 5.8], p 0.001). This increase was driven by the use of antidepressants (odds ratio = 6.4, 95% confidence interval = [4.2, 9.5], p 0.001) and anticonvulsants (odds ratio = 4.4, 95% confidence interval = [1.8, 11.1]) and modest increases in the use of anxiolytic agents (odds ratio = 1.9, 95% confidence interval = [1.1, 3.1]) and sedatives (odds ratio = 1.7, 95% confidence interval = [1.6, 1.9]). The prevalence of any psychotropic medication use increased with increasing age (40–59.9 years: odds ratio = 1.9, 95% confidence interval = [1.5, 2.6] 60–79.9 years: odds ratio = 2.6, 95% confidence interval = [1.9, 3.5], compared to the 20- to 39.9-year group). Use of selective serotonin reuptake inhibitors increased dramatically over the study period (odds ratio = 15.3, 95% confidence interval = [7.0, 33.4]). Use of psychotropic medication has increased substantially over the past two decades, especially among older women. Further investigations into the correlates and outcomes of the increased use of psychotropic medications are warranted.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.JAD.2009.10.027
Abstract: The clinical significance of subthreshold mixed states is unclear. This study investigated the clinical outcomes in participants with bipolar I disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively. Participants (N=239) in a prospective observational study of treatment and outcomes in bipolar I or schizoaffective disorder, bipolar type, were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3 months over a 24-month period. Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. A depressive mixed state was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression. In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.NEUBIOREV.2014.05.007
Abstract: Many studies support a crucial role for oxidative & nitrosative stress (O&NS) in the pathophysiology of unipolar and bipolar depression. These disorders are characterized inter alia by lowered antioxidant defenses, including: lower levels of zinc, coenzyme Q10, vitamin E and glutathione increased lipid peroxidation damage to proteins, DNA and mitochondria secondary autoimmune responses directed against redox modified nitrosylated proteins and oxidative specific epitopes. This review examines and details a model through which a complex series of environmental factors and biological pathways contribute to increased redox signaling and consequently increased O&NS in mood disorders. This multi-step process highlights the potential for future interventions that encompass a erse range of environmental and molecular targets in the treatment of depression.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.BBR.2008.11.017
Abstract: Oxidative stress and reduced brain glutathione (GSH) levels have been reported in psychiatric illnesses including schizophrenia and bipolar disorder. However the role of GSH in cognitive impairment in the illness remains unclear. Treatment of Sprague-Dawley rats and C57Bl/6 mice with 2-cyclohexene-1-one (CHX) dose-dependently reduced striatal and frontal cortical GSH levels similar to those in schizophrenia. In both species, GSH depletion resulted in disruption of short-term spatial recognition memory in a Y-maze test. In conclusion, GSH depletion induces cognitive impairment, which may be relevant to the role of GSH in psychiatric illnesses.
Publisher: Korean College of Neuropsychopharmacology
Date: 31-05-2022
Publisher: American Medical Association (AMA)
Date: 10-11-2020
Publisher: Oxford University Press (OUP)
Date: 30-11-2018
Publisher: Springer Science and Business Media LLC
Date: 24-05-2013
Publisher: Elsevier BV
Date: 10-2019
Publisher: Springer Science and Business Media LLC
Date: 14-11-2008
Abstract: In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2015
Publisher: Springer Science and Business Media LLC
Date: 03-11-2020
DOI: 10.1038/S41380-020-00925-X
Abstract: The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.
Publisher: Frontiers Media SA
Date: 04-09-2019
Publisher: Cambridge University Press (CUP)
Date: 18-12-2018
DOI: 10.1017/S0033291718003690
Abstract: Elevated levels of pro-inflammatory cytokines are consistently reported in schizophrenia (SZ) and bipolar-I disorder (BD), as well as among in iduals who have been exposed to childhood trauma. However, higher levels of inflammatory markers in these disorders are yet to be investigated with respect to levels of exposure to different types of childhood trauma. Participants were 68 cases with a diagnosis of schizophrenia/schizoaffective disorder (SZ), 69 cases with a diagnosis of psychotic BD and 72 healthy controls (HC). Serum levels of interleukin 6 (IL-6), tumour necrosis factor- α (TNF- α ) and C-reactive protein (CRP) were quantified, and childhood trauma exposure was assessed with the Childhood Trauma Questionnaire. The SZ group had significantly higher levels of IL-6, TNF- α and CRP when compared with the HC group (all p 0.05, d = 0.41–0.63), as well as higher levels of TNF- α when compared with the BD group ( p = 0.014, d = 0.50) there were no differences between the BD and HC groups for any markers. Exposure to sexual abuse was positively associated (standardised β = 0.326, t = 2.459, p = 0.018) with levels of CRP in the SZ group, but there were no significant associations between any form of trauma exposure and cytokine levels in the HC or BD groups. These results contribute to the evidence for a chronic state of inflammation in SZ but not BD cases. Differential associations between trauma exposure and levels of pro-inflammatory cytokines across the diagnostic categories suggest that trauma may impact biological (stress and immune) systems differently in these patient groups.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.JAD.2016.02.018
Abstract: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. Study limitations include the small s le size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions.
Publisher: Informa UK Limited
Date: 09-05-2019
Publisher: Elsevier BV
Date: 2020
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.JAD.2019.02.013
Abstract: Bipolar disorder is a chronic, episodic mental illness, affecting around 2.4% of the population worldwide. Psychological and/or physiological comorbidities are a common consequence, and osteoporosis is one such possible comorbidity. Thus, this systematic review aimed to collate, evaluate, and discuss the literature examining the link between bipolar disorder and bone health. We conducted an e-search of PubMed/OVID/MEDLINE, PsychINFO and CINAHL to identify studies that investigated associations between bipolar disorder and bone in adults aged ≥18. Two reviewers determined eligibility according to pre-determined criteria, and methodological quality was assessed using a previously published methodological scoring system. Due to heterogeneity, a best-evidence synthesis was performed. Our search yielded 1409 articles, of which three (all cohorts) met predetermined criteria. The studies from Taiwan and the United States of America analysed administrative data, albeit spanning different years, and comprised a total of 344,497 participants. No studies investigating bone quantity or quality were identified. Bipolar disorder was associated with an increased risk of fracture (range 20-80%) and fracture-free survival time for those with bipolar disorder decreased substantially with advancing age, and for women (10-30% shorter than men). Fracture incidence per 1000 person years (py) was 21.4 and 10.8 in those with and without bipolar disorder, respectively. Limited data and marked methodological heterogeneity prevented the pooling of these data for a numerical synthesis. Increased fracture risk was observed in in iduals with bipolar disorder, independent of older age, sex, comorbidities and medication use. The operative mechanisms, risk and treatment factors warrant further enquiry.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Springer Science and Business Media LLC
Date: 11-04-2022
DOI: 10.1007/S13311-022-01229-4
Abstract: In the face of a global epidemic of drug addiction, neglecting to develop new effective therapies will perpetuate the staggering human and economic costs of substance use. This review aims to summarize and evaluate the preclinical and clinical studies of deep brain stimulation (DBS) as a novel therapy for refractory addiction, in hopes to engage and inform future research in this promising novel treatment avenue. An electronic database search (MEDLINE, EMBASE, Cochrane library) was performed using keywords and predefined inclusion criteria between 1974 and 6/18/2021 (registered on Open Science Registry). Selected articles were reviewed in full text and key details were summarized and analyzed to understand DBS’ therapeutic potential and possible mechanisms of action. The search yielded 25 animal and 22 human studies. Animal studies showed that DBS of targets such as nucleus accumbens (NAc), insula, and subthalamic nucleus reduces drug use and seeking. All human studies were case series/reports (level 4/5 evidence), mostly targeting the NAc with generally positive outcomes. From the limited evidence in the literature, DBS, particularly of the NAc, appears to be a reasonable last resort option for refractory addictive disorders. We propose that future research in objective electrophysiological (e.g., local field potentials) and neurochemical (e.g., extracellular dopamine levels) biomarkers would assist monitoring the progress of treatment and developing a closed-loop DBS system. Preclinical literature also highlighted the prefrontal cortex as a promising DBS target, which should be explored in human research.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/BDI.12486
Abstract: Many people experience irritability when manic, hypomanic, or depressed, yet its impact on illness severity and quality of life in bipolar and schizoaffective disorders is poorly understood. This study aimed to examine the relationship between irritability and symptom burden, functioning, quality of life, social support, suicidality, and overall illness severity in a naturalistic cohort of people with bipolar I or schizoaffective disorder. We used data from 239 adult outpatients with bipolar I or schizoaffective disorder in the Bipolar Comprehensive Outcomes Study (BCOS) - a non-interventional observational study with a 2-year follow-up period. Baseline demographic and clinical characteristics of participants with and without irritability were compared. A mixed-model repeated measures analysis was conducted to examine the longitudinal effect of irritability on clinical and quality-of-life variables over follow-up using significant baseline variables. At baseline, 54% of participants were irritable. Baseline irritability was associated with illness severity, mania, depression, psychotic symptoms, suicidality, poor functioning, and quality of life, but not diagnosis (schizoaffective/bipolar disorder). Participants with irritability were less likely to have a partner and perceived less adequate social support. On average, over follow-up, those with irritability reported more symptoms, functional impairment, and suicidality. Furthermore, the effects of irritability could not be fully explained by illness severity. Irritability was associated with more negative symptomatic, functional, and quality-of-life outcomes and suicidality. The identification, monitoring, and targeted treatment of irritability may be worth considering, to enhance health and wellbeing outcomes for adults with bipolar and schizoaffective disorders.
Publisher: MDPI AG
Date: 06-11-2020
DOI: 10.3390/IJMS21218333
Abstract: Although neurogenesis is affected in several psychiatric diseases, the effects and mechanisms of action of psychoactive drugs on neurogenesis remain unknown and/or controversial. This study aims to evaluate the effects of psychoactive drugs on the expression of genes involved in neurogenesis. Neuronal-like cells (NT2-N) were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), or valproate (0.5 mM) for 24 h. Genome wide mRNA expression was quantified and analysed using gene set enrichment analysis, with the neurogenesis gene set retrieved from the Gene Ontology database and the Mammalian Adult Neurogenesis Gene Ontology (MANGO) database. Transcription factors that are more likely to regulate these genes were investigated to better understand the biological processes driving neurogenesis. Targeted metabolomics were performed using gas chromatography-mass spectrometry. Six of the eight drugs decreased the expression of genes involved in neurogenesis in both databases. This suggests that acute treatment with these psychoactive drugs negatively regulates the expression of genes involved in neurogenesis in vitro. SOX2 and three of its target genes (CCND1, BMP4, and DKK1) were also decreased after treatment with quetiapine. This can, at least in part, explain the mechanisms by which these drugs decrease neurogenesis at a transcriptional level in vitro. These results were supported by the finding of increased metabolite markers of mature neurons following treatment with most of the drugs tested, suggesting increased proportions of mature relative to immature neurons consistent with reduced neurogenesis.
Publisher: JMIR Publications Inc.
Date: 24-11-2019
Abstract: mproved understanding of social constructs around injury may help insurance case managers to understand how best to support people after injury. his study sought to explore what people who sustain work-related injuries may seek from online communities. The study highlights potential opportunities for improved engagement with insurance case management practice. n observational netnographic analysis was undertaken on anonymous, publicly available messages posted on Australian message boards. All research data were drawn from anonymous, online communities. A person (author SM) with experience of making a claim through an Australian workers’ compensation system and online engagement was involved in study conception, design, and analysis. Data were analyzed using NVivo12 in an iterative, multistage process including coding, journaling, and member checking. A total of 141 people were engaged in discussion across 47 threads housed on 4 Australian forums. n this qualitative study, themes emerged from the data, describing how injured workers use online communities to help make decisions, get support, and solve problems. The key motivators for action and engagement were seeking information, connection, or justice. Establishment of relationships was a key mediator of each of these parameters. ome work-related injuries may involve medical and medicolegal complexity as well as changed lifestyle and routine during convalescence and recovery. The mechanism used by some injured workers to seek information and problem solve suggests a capacity for self-management and self-care after work-related injury. Netnography provides information on a community that may not regularly engage with research because of the complexity of their situation and their vulnerability.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2023
DOI: 10.1038/S41398-023-02501-7
Abstract: The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone aliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37 18.6 Mage [2.9] years 21 women placebo group: 39 18.3 Mage [2.7] 22 women) and 42 healthy controls (19.2 Mage [3.0] years 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall ( p = 0.023), verbal learning ( p = 0.024) and delayed recall ( p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024 η p 2 = 0.062 verbal learning: p = 0.015 η p 2 = 0.072 both medium effects delayed recall: p = 0.001 η p 2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone aliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis. Trial registration: Australian New Zealand Clinical Trials Registry ( www.anzctr.org.au/ ACTRN12607000608460).
Publisher: Informa UK Limited
Date: 21-03-2022
DOI: 10.1080/15622975.2021.2013041
Abstract: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support ( recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.
Publisher: Cambridge University Press (CUP)
Date: 20-03-2017
DOI: 10.1017/NEU.2017.2
Abstract: This study aimed to explore effects of adjunctive N -acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression. We embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum s les at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment. NAC treatment significantly improved depressive symptoms on the Montgomery–Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment. Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.
Publisher: Wiley
Date: 2010
DOI: 10.1002/HUP.1081
Abstract: Medication adherence contributes to the efficacy-effectiveness gap of treatment in patients with bipolar disorder. This paper aims to examine the challenges involved in improving medication adherence in bipolar disorder, and to extract some suggestions for future directions from the core psychosocial studies that have targeted adherence as a primary or secondary outcome. A search was conducted for articles that focused on medication adherence in bipolar disorder, with emphasis on publications from 1996 to 2008 using Medline, Web of Science, CINAHL PLUS, and PsychINFO. The following key words were used: adherence, compliance, alliance, adherence assessment, adherence measurement, risk factors, psychosocial interventions, and psycho-education. There are a number of challenges to understanding non-adherence including the difficulty in defining and measuring it and the various risk factors that need to be considered when aiming to enhance adherence. Nevertheless, the importance of addressing adherence is evidenced by the connection between adherence problems and poor outcome. Despite these challenges, a number of small psychosocial studies targeting adherence as a primary outcome point to the potential usefulness of psycho-education aimed at improving knowledge, attitudes, and adherence behavior, but more large scale randomized controlled trials are needed in this area. Evidence of improved outcomes from larger randomized controlled trials of psychosocial interventions that target medication adherence as a secondary outcome suggests that tackling other factors besides medication adherence may also be an advantage. While some of these larger studies demonstrate an improvement in medication adherence, the translation of these interventions into real life settings may not always be practical. A person centered approach that considers risk factors for non-adherence and barriers to other health behaviors may assist with the development of more targeted briefer interventions. Integral to improving medication adherence is the delivery of psycho-education, and attention needs to be paid to the implementation, and timing of psycho-education. Progress in the understanding of how medicines work may add to the credibility of psycho-education in the future. Enhancement of treatment adherence in bipolar patients is a necessary and promising management component as an adjunct to pharmacotherapy. The current literature on psychosocial interventions that target medication adherence in bipolar disorder points to the possibility of refining the concept of non-adherence and adapting psycho-education to the needs of certain subgroups of people with bipolar disorder. Large scale randomized controlled trials of briefer or more condensed interventions are needed that can inform clinical practice.
Publisher: Informa UK Limited
Date: 03-06-2019
DOI: 10.1080/09637486.2019.1614540
Abstract: Beyond being a source of key nutrients, bovine milk influences physiological functions by synthesising bioactive peptides during the process of digestion. Some of the claimed negative health outcomes associated with milk consumption, such as cardiovascular diseases and type 1 diabetes may be attributed to an opioid peptide, beta-casomorphin-7 (BCM-7), derived from A1 beta-casein. BCM-7 exerts its function by binding to the μ-opioid receptors in the body. It is hypothesised that activation of the μ-opioid receptors in the gut can alter gut microbial composition, impair gut barrier integrity and bile acid metabolism, in addition to increasing gastrointestinal transit time and gut inflammation. Further, it is hypothesised that BCM-7 may influence fractures and obesity via μ-opioid receptor pathways. In conclusion, it appears that BCM-7 might have multiple functions pertinent to human health however, the evidence is limited and warrants further pre-clinical and clinical studies for hypothesis confirmation.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/809653
Abstract: Use of complementary medicines and therapies (CAM) and modification of lifestyle factors such as physical activity, exercise, and diet are being increasingly considered as potential therapeutic options for anxiety disorders. The objective of this metareview was to examine evidence across a broad range of CAM and lifestyle interventions in the treatment of anxiety disorders. In early 2012 we conducted a literature search of PubMed, Scopus, CINAHL, Web of Science, PsycInfo, and the Cochrane Library, for key studies, systematic reviews, and metaanalyses in the area. Our paper found that in respect to treatment of generalized anxiety or specific disorders, CAM evidence revealed current support for the herbal medicine Kava. One isolated study shows benefit for naturopathic medicine, whereas acupuncture, yoga, and Tai chi have tentative supportive evidence, which is h ered by overall poor methodology. The breadth of evidence does not support homeopathy for treating anxiety. Strong support exists for lifestyle modifications including adoption of moderate exercise and mindfulness meditation, whereas dietary improvement, avoidance of caffeine, alcohol, and nicotine offer encouraging preliminary data. In conclusion, certain lifestyle modifications and some CAMs may provide a beneficial role in the treatment of anxiety disorders.
Publisher: Wiley
Date: 15-04-2022
DOI: 10.1111/BDI.13208
Abstract: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well‐characterized s les of in iduals with BD. Thirteen cohorts from 7 countries included n = 5882 in iduals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived “higher versus lower function” as the dependent variable and selected clinical and demographic variables as predictors. We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. The bipolar clinical research community is poised to work together to characterize the multi‐dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large‐scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every in idual with this illness.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2019
DOI: 10.1186/S13063-019-3786-5
Abstract: First-episode psychosis (FEP) may lead to a progressive, potentially disabling and lifelong chronic illness however, evidence suggests that the illness course can be improved if appropriate treatments are given at the early stages. Nonetheless, the efficacy of antipsychotic medications is suboptimal, particularly for negative and cognitive symptoms, and more efficacious and benign treatments are needed. Previous studies have shown that the antioxidant amino acid N -acetylcysteine (NAC) reduces negative symptoms and improves functioning in chronic schizophrenia and bipolar disorder. Research is scarce as to whether NAC is beneficial earlier in the course of illness. The primary aim of this study is to determine the efficacy of treatment with adjunctive NAC (2 g/day for 26 weeks) compared with placebo to improve psychiatric symptoms in young people experiencing FEP. Secondary aims are to explore the neurobiological mechanisms underpinning NAC and how they relate to various clinical and functional outcomes at 26- and 52-week follow-ups. ENACT is a 26-week, randomised controlled trial of adjunctive NAC versus placebo, with a 26-week non-treatment follow-up period, for FEP. We will be recruiting 162 young people aged 15–25 years who have recently presented to, and are being treated at, the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia. The primary outcome is the Total Score on the Positive and Negative Syndrome Scale which will be administered at baseline, and weeks 4, 8, 12, 26 (primary endpoint), and 52 (end of study). Secondary outcomes include: symptomatology, functioning, quality of life, neurocognition, blood-derived measures of: inflammation, oxidative and nitrosative stress, and magnetic resonance spectroscopy measures of glutathione concentration. Targeted drug development for FEP to date has generally not involved the exploration of neuroprotective agents. This study has the potential to offer a new, safe, and efficacious treatment for people with FEP, leading to better treatment outcomes. Additionally, the neuroprotective dimension of this study may lead to a better long-term prognosis for people with FEP. It has the potential to uncover a novel treatment that targets the neurobiological mechanisms of FEP and, if successful, will be a major advance for psychiatry. Australian New Zealand Clinical Trials Registry, ID: ACTR N12618000413224 . Registered on 21 March 2018.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.JAD.2016.02.029
Abstract: According to a recent position paper by the American Heart Association, it remains unclear whether depression is a risk factor for incident Coronary Heart Disease (CHD). We assessed whether a depressive disorder independently predicts 18-year incident CHD in women. A prospective longitudinal study of 860 women enrolled in the Geelong Osteoporosis Study (1993-2011) was conducted. Participants were derived from an age-stratified, representative s le of women (20-94 years) randomly selected from electoral rolls in South-Eastern Australia. The exposure was a diagnosis of a depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Outcomes data were collected from hospital medical records: (1) PRIMARY OUTCOME: a composite measure of cardiac death, non-fatal Myocardial Infarction or coronary intervention. (2) Secondary outcome: any cardiac event (un/stable angina, cardiac event not otherwise defined) occurring over the study period. Seven participants were excluded based on CHD history. Eighty-three participants (9.6%) recorded ≥1 cardiac event over the study period 47 had a diagnosis that met criteria for inclusion in the primary analysis. Baseline depression predicted 18-year incidence, adjusting for (1) anxiety (adj. OR:2.39 95% CIs:1.19-4.82), plus (2) typical risk factors (adj. OR:3.22 95% CIs:1.45-6.93), plus (3) atypical risk factors (adj. OR:3.28 95% CIs:1.36-7.90). This relationship held when including all cardiac events. No relationship was observed between depression and recurrent cardiac events. The results of this study support the contention that depression is an independent risk factor for CHD incidence in women. Moreover, the strength of association between depression and CHD incidence was of a greater magnitude than any typical and atypical risk factor.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2015
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/13651500701246088
Abstract: Objective. This pilot study aimed to determine whether a group based psychosocial intervention reduced rates of relapse, improved function and quality of life in people with bipolar disorder. Method. Patients with a diagnosis of bipolar disorder, types I and II were recruited in the Geelong Region of Victoria. Patients were assessed at baseline for psychiatric status, mood episode, function, and medication adherence. They were randomly assigned to either the intervention arm, a 12-week, structured group-based therapy as an adjunct to treatment as usual or the control arm, which consisted of treatment as usual, plus weekly phone calls. Participants were then followed up for a period of 3 months and assessed by a researcher blinded to treatment and control interventions. Results. Functioning as measured by the Global Assessment of Functioning (GAF) was significantly improved in the intervention group (P=0.008). The social relationships subscale on the (WHOQoL-BREF) showed significant results (P<0.05 level). There was also a positive trend in reduction of relapses in the intervention group. Conclusion. The use of a group intervention for bipolar disorder as an adjunct to usual treatment has potential benefits, both in reduction of relapse and improvement in functionality, and may be a cost effective way of delivering psychosocial treatments.
Publisher: SAGE Publications
Date: 23-10-2015
Publisher: Springer Science and Business Media LLC
Date: 14-03-2014
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.JAD.2007.01.027
Abstract: There are obstacles to early identification of bipolar disorder. Identifying and treating illness early in its time course may be associated with a better prognosis. A questionnaire was administered at interview, when the participant was euthymic, to participants (n=240) enrolled in the Bipolar Comprehensive Outcomes Study (BCOS). Information was collected about the sequential timeline of specific symptoms of mental illness up to when they first received a diagnosis of Bipolar Disorder or Schizoaffective Disorder. Any symptoms of mental illness were first experienced at 17.5 years (median Inter Quartile Range (IQR) 13.8-24.3 n=216) and mood swings at 18.0 years (IQR 14-25 n=197). Symptoms of depression were experienced at 18.0 years (IQR 14-25 n=197), a full episode of depression at 21.2 years (IQR 17-28.5 n=200), symptoms of mania at 21.0 years (IQR 16.8-29.5 n=212) and a full episode of mania at 24.1 years (IQR 19-30.5 n=205). Medical treatment was sought at 24.0 years (IQR 19-31.5 n=217). Participants received a diagnosis of Bipolar Disorder or Schizoaffective Disorder at 30.0 years (IQR 23-37.3 n=215). Having had a previous diagnosis other than Bipolar Disorder or Schizoaffective Disorder was reported by 120 of 216 participants who answered this question, most commonly unipolar depression (26.6%). Diagnostic delay was greater in in iduals with early onset disorder. Participants typically experience a long sequential course of symptoms, episodes, treatments and diagnosis. The polarity of onset is most commonly depressive, and subthreshold symptoms tend to precede threshold symptoms of both polarities. Data were collected retrospectively.
Publisher: Springer Science and Business Media LLC
Date: 20-06-2020
Publisher: Springer Science and Business Media LLC
Date: 15-06-2022
DOI: 10.1186/S12888-022-04034-7
Abstract: Financial distress is thought to be a key reason why small-medium enterprise (SME) owners experience higher levels of mental health conditions compared with the broader population. Business advisors who form trusting, high-quality relationships with their SME clients, are therefore well placed to: (1) help prevent/reduce key sources of financial distress, (2) better understand the business and personal needs of their clients and, (3) recognise the signs and symptoms of mental health conditions and encourage help-seeking where appropriate. The aim of this study is to compare the effectiveness of relationship building training (RBT) combined with mental health first aid (MHFA) training for business advisors with MHFA alone, on the financial and mental health of their SME-owner clients. This is a single blind, two-arm randomised controlled trial. Participants will be business advisors who provide information, guidance and/or assistance to SME owner clients and are in contact with them at least 3 times a year. The business advisors will invite their SME-owner clients to complete 3 online surveys at baseline, 6- and 12-months. Business advisors will be randomised to one of two conditions, using a 1:1 allocation ratio: (1) MHFA with RBT or (2) MHFA alone, and complete 3 online surveys at baseline, 2- and 6-months. Primary outcomes will be measured in the business advisors and consist of the quality of the relationship, stigmatizing attitude, confidence to offer mental health first aid, quality of life and provision of mental health first aid. Secondary outcomes will be measured in the SME owners and includes trust in their business advisors, the quality of this relationship, financial wellbeing, financial distress, psychological distress, help-seeking behaviour, and quality of life. To complement the quantitative data, we will include a qualitative process evaluation to examine what contextual factors impacted the reach, effectiveness, adoption, implementation, and maintenance of the training. As there is evidence for the connections between client trust, quality of relationship and financial and mental wellbeing, we hypothesise that the combined RBT and MHFA training will lead to greater improvements in these outcomes in SME owners compared with MHFA alone. ClinicalTrials.gov : NCT04982094 . Retrospectively registered 29/07/2021. The study started in February 2021 and the recruitment is ongoing.
Publisher: SAGE Publications
Date: 13-08-2014
Abstract: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. Traumatic events were retrospectively evaluated from patient files in a s le of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the s le. Participants with past direct-personal trauma had significantly higher symptoms of mania ( p=0.02), depression ( p=0.03) and psychopathology ( p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant ( p=0.05) however, participants with past direct-personal trauma had significantly poorer social and occupational functioning ( p=0.04) at the 12-month assessment with medium effect. Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent in iduals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.
Publisher: Wiley
Date: 10-2014
DOI: 10.1002/WPS.20144
Publisher: SAGE Publications
Date: 09-09-2022
DOI: 10.1177/00048674221123494
Abstract: While two editorials have raised concerns about the decline in Australian academic psychiatry, for a genuine rejuvenation to ever occur, we will need to re-examine how women can be better included in this important endeavour. While attainment of fellowship has reached gender parity, academic psychiatry has disappointingly lagged, with 80% of its senior leadership roles across Australia and New Zealand still held by men, with a similar situation in the United Kingdom and the United States as well as many other countries. Encouraging women into academic psychiatry is not only critical to progress as a profession but also will help address the current blindness to sex differences in biological psychiatry, as well the social impact of restrictive gender norms and the effects of gender-based violence on mental health. This potentially creates opportunities for significant gains and insights into mental disorders. However, addressing the barriers for women in academia requires tackling the entrenched disparities across salaries, grant funding, publications, teaching responsibilities, keynote invitations and academic promotions alongside the gender-based microaggressions, harassment and tokenism reported by many of our female academics. Many women must grapple with not just a ‘second shift’ but a ‘third shift’, making the burden of an academic career unreasonable and burnout more likely. Addressing this is no easy task. The varied research in academic medicine reveals no quick fixes, although promoting gender equity brings significant potential benefits. Areas such as academic psychiatry need to recognise our community’s growing discomfort with workplaces that choose to maintain status quo. Gender equity must be a critical part of any quest to revive this important area of practice for our profession.
Publisher: Wiley
Date: 28-01-2019
DOI: 10.1111/EIP.12775
Abstract: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential. Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin. Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen. Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.
Publisher: Physicians Postgraduate Press, Inc
Date: 21-09-2011
Publisher: Wiley
Date: 30-05-2023
DOI: 10.1111/ADD.16230
Abstract: To determine whether the risk of psychotic symptoms during weeks of meth hetamine use was dependent on, increased by, or independent of having a family history of psychosis. Secondary analysis of 13 contiguous 1‐week periods of data (1370 weeks). A risk modification framework was used to test each scenario. Geelong, Wollongong and Melbourne, Australia. Participants in a randomized controlled trial of treatment for meth hetamine dependence ( n = 148) who did not have a primary psychotic disorder on enrolment. Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) meth hetamine use in the previous week was assessed using the Timeline Followback method. Self‐reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis. The risk of psychotic symptoms in the past week was independently associated with meth hetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3–4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9–7.0) the joint risk among participants with a family history of psychosis during weeks when they were using meth hetamine was large (RR = 4.0, 95% CI = 2.0–7.9). There was no significant interaction between a family history of psychosis and meth hetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3–1.8), but there was a small non‐significant excess risk due to the interaction (0.20 95% CI = −1.63 to 2.03). Among people dependent on meth hetamine, the relative risk of psychotic symptoms during weeks of meth hetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JAD.2015.03.041
Abstract: This study examines the effects of malondialdehyde (MDA) and uric acid on insulin resistance and atherogenicity in subjects with and without mood disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). We included 314 subjects with depression and bipolar depression, with and without the MetS and TUD and computed insulin resistance using the updated homeostasis model assessment (HOMA2IR) and atherogenicity using the atherogenic index of plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL) cholesterol. HOMA2IR is correlated with body mass index (BMI) and uric acid levels, but not with mood disorders and TUD, while the AIP is positively associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid is positively associated with insulin and triglycerides and negatively with HDL cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood disorders and TUD further increase AIP but not insulin resistance. Glucose is positively associated with increasing age, male gender and BMI. The results show that mood disorders, TUD and BMI together with elevated levels of uric acid and MDA independently contribute to increased atherogenic potential, while BMI and uric acid are risk factors for insulin resistance. The findings show that mood disorders and TUD are closely related to an increased atherogenic potential but not to insulin resistance or the MetS. Increased uric acid is a highly significant risk factor for insulin resistance and increased atherogenic potential. MDA, a marker of lipid peroxidation, further contributes to different aspects of the atherogenic potential. Mood disorders and TUD increase triglyceride levels, lower HDL cholesterol and are strongly associated with the atherogenic, but not insulin resistance, component of the MetS.
Publisher: Wiley
Date: 30-05-2017
DOI: 10.1111/DAR.12414
Abstract: Meth hetamine dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of meth hetamine dependence. N-acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N-acetylcysteine also has antioxidant properties that protect against meth hetamine-induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of meth hetamine. This commentary overviews the actions of N-acetylcysteine and evidence for its efficacy in treating addiction with a particular focus on its potential utility for meth hetamine dependence. We conclude that the preliminary evidence indicates a need for full-scale trials to definitively establish whether N-acetylcysteine has a therapeutic benefit and the nature of this benefit, for managing meth hetamine dependence. [McKetin R, Dean O, Baker A. L, Carter G, Turner A, Kelly P. J, Berk M. A potential role for N-acetylcysteine in the management of meth hetamine dependence. Drug Alcohol Rev 2017 :153-159].
Publisher: BMJ
Date: 04-2019
DOI: 10.1136/BMJOPEN-2018-025145
Abstract: Remission rates for mood disorders, including depressive and bipolar disorders, remain relatively low despite available treatments, and many patients fail to respond adequately to these interventions. Evidence suggests that personality disorder may play a role in poor outcomes. Although personality disorders are common in patients with mood disorders, it remains unknown whether personality disorder affects treatment outcomes in mood disorders. We aim to review currently available evidence regarding the role of personality disorder on pharmacological interventions in randomised controlled trials for adults with mood disorders. A systematic search of Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com, PubMed via PubMed, EMBASE via embase.com, PsycINFO via Ebsco and CINAHL Complete via Ebsco databases will be conducted to identify randomised controlled trials that have investigated pharmacological interventions in participants aged 18 years or older for mood disorders (ie, depressive disorders and bipolar spectrum disorders) and have also included assessment of personality disorder. One reviewer will screen studies against the predetermined eligibility criteria, and a second reviewer will confirm eligible studies. Data will be extracted by two independent reviewers. Methodological quality and risk of bias will be assessed using the Cochrane Risk of Bias tool. A systematic review, and if sufficient evidence is identified, a meta-analysis will be completed. Meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. A random effects model will be employed and statistical heterogeneity will be evaluated using the I 2 statistic. Prespecified subgroup analyses will be completed. As this systematic review will use published data, ethics permission will not be required. The outcomes of this systematic review will be published in a relevant scientific journal and presented at a research conference. CRD42018089279.
Publisher: SAGE Publications
Date: 15-03-2021
Abstract: Effective treatment of depression is a key target for suicide prevention strategies. However, only around one-third of young people with suicide risk respond to evidence-based treatments. Understanding the trajectory of suicidal ideation, as a marker of suicide risk, over the course of evidence-based treatment for depression might provide insight into more targeted and effective treatments. This is a secondary analysis of data from the multicentre Youth Depression Alleviation–Combined Treatment trial. A total of 153 young people aged 15–25 years diagnosed with major depressive disorder were randomly assigned in this double-blind, placebo-controlled trial to either cognitive behavioural therapy plus fluoxetine or cognitive behavioural therapy plus placebo. Participants were assessed for depression and suicidal ideation at baseline and at weeks 4, 8 and 12. Using group-based trajectory modelling, we identified two distinct depression trajectories. The first (Improving 54.9% n = 83) comprised those who experienced a consistent decline in depression symptoms. The second (Persisting 45.1% n = 70) comprised those who, despite treatment, still had clinically significant levels of depression by the end of treatment. For suicidal ideation, we identified four distinct trajectories: Non-clinical (15.5% n = 20), Low Improving (47.1% n = 75), High Improving (24.8% n = 38) and High Persisting (12.7% n = 20). Treatment allocation was not significantly associated with trajectory membership for either depression or suicidal ideation. Understanding the course of depression and suicidal ideation during treatment has important implications for managing suicide risk. The findings suggest that there is an identifiable group of young people for whom enhanced psychological and/or pharmacological intervention might be required to ensure a better treatment response. Specific interventions for those with suicidal ideation may also be prudent from the outset. The Youth Depression Alleviation–Combined Treatment trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612001281886).
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/BDI.13035
Abstract: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg To develop the MDcpg The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response. The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg
Publisher: Physicians Postgraduate Press, Inc
Date: 14-12-2010
Publisher: Public Library of Science (PLoS)
Date: 15-09-2022
DOI: 10.1371/JOURNAL.PONE.0274271
Abstract: Both albuminuria and depression are associated with cardiovascular disease, reflecting low-grade systemic inflammation and endothelial dysfunction. They share risk factors including weight, blood pressure, smoking and blood glucose levels. This longitudinal study aimed to examine bidirectional associations between depression symptoms, indexed by the Hospital Anxiety and Depression scale (HADS), and the inflammation marker albuminuria. 2909 persons provided urine s les in both the second (HUNT2, 1995–97) and third wave (HUNT3, 2006–2008) of the Trøndelag Health Survey, Norway. We used a generalized linear regression model (GLM) and ANOVA to assess the association between albuminuria levels (exposure HUNT2) with depression symptoms (outcome in HUNT3) and between depression symptoms (exposure HUNT2) with albuminuria (outcome HUNT3). Depression symptoms were measured with the HADS Depression Scale, analyzed utilising the full 7 items version and analyses restricted to the first 4 items (HADS-D and HADS-4). We accounted for confounders including baseline in idual levels of the exposure variables. In this 10-years follow-up study, we found no statistical evidence for an association between baseline depression symptoms and subsequent albuminuria, nor between baseline albuminuria and subsequent depression symptoms. For albuminuria, only 0.04% was explained by prior depression, and for depression, only 0.007% was explained by previous albuminuria levels. The results were essentially the same for the shorter HADS-4 measure. There does not appear to be a longitudinal association between albuminuria and depression measured by the HADS.
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/BDI.13036
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.NEUBIOREV.2018.04.002
Abstract: Disruptions of bioenergetic signaling and neurogenesis are hallmarks of depression physiology and are often the product of dysregulation of the inflammatory, stress-response, and metabolic systems. These systems are extensively interrelated at the physiological level, yet the bulk of the literature to date addresses pathophysiological mechanisms in isolation. A more integrated understanding of the etiology, progression, and treatment response profiles of depression is possible through wider consideration of relevant preclinical and clinical studies that examine the result of disruptions in these systems. Here, we review recent data demonstrating the critical effects of bioenergetic disruption on neuroplasticity and the development and progression of depressive illness. We further highlight the interactive and dynamic nature of the inflammatory and stress response systems and how disruption of these systems influences bioenergetic signaling pathways critical to treatment outcomes. In so doing, we underscore the pressing need to reconsider the implications of treatment resistance and present a framework for developing novel, personalized treatment approaches for depression.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.JAD.2010.04.001
Abstract: The validity of schizoaffective disorder (SA) diagnosis has for long been a matter of controversy and its delineation from bipolar I disorders (BD) has often been questioned. However, most studies have been conducted in chronic s les and have therefore been biased towards patients with poorer outcome, which may have h ered the possibility to identify significant differences between both diagnoses. 108 subjects presenting a first DSM-III-R manic episode with psychotic features were assessed at baseline and 12 months after stabilisation on symptoms and functional characteristics, and patients with BD (n=87) were compared with those with SA bipolar subtype (SAB) (n=21). SAB patients had a higher prevalence of first degree relatives with schizophrenia and a lower premorbid functional level. They had a longer prodromal phase, a longer duration of untreated psychosis and remained symptomatic for a longer period. They also had higher levels of positive symptoms in the acute manic phase however, with two exceptions, the type of psychotic symptoms were similar in both groups. At stabilisation and 12 months after stabilisation, SA patients had higher levels of negative symptoms, with poorer functional level at 12 months. These data suggest SA is a valid diagnosis in the early phase of psychotic disorders considering it defines a subgroup of first episode psychotic mania patients with distinct characteristics compared to BD. While a dimensional approach to diagnosis may be more adapted to this phase of illness, SA disorder offers, in the context of categorical classifications, a useful intermediate category that reflects a clinical reality.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2015
DOI: 10.1038/TP.2014.134
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.PBB.2010.08.013
Abstract: Oxidative stress has been implicated in several psychiatric illnesses, including schizophrenia. Glutathione is the brain's primary antioxidant and decreased levels of brain glutathione are reported in schizophrenia. Prepulse inhibition (PPI) is a measure of sensory gating, and PPI is reduced in schizophrenia. This study aimed to investigate the effects of brain glutathione depletion on PPI regulation. Rats and mice were treated with the glutathione-depleting agent, 2-cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by treatment with hetamine and MK-801. Treatment with CHX caused significant depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI and startle were not altered. However, the disruption of PPI after treatment with hetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was not altered by CHX-treatment, nor was there any effect of CHX treatment in mice. These data show an interaction of glutathione depletion with the effects of hetamine treatment on PPI in rats. This effect could reflect loss of plasticity in PPI regulation caused by the additive effects of CHX-induced glutathione depletion and additional oxidative stress caused by hetamine-induced dopamine release. The significance of these results for schizophrenia is discussed.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JAD.2018.08.011
Abstract: The aim of current study is to assess the cross-sectional association of chronic non-communicable diseases (diabetes mellitus, arthritis, asthma, chronic lung disease, angina, and stroke) with both diagnosed and undiagnosed depression in the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 1, a study of adults in six low- and middle-income countries. A total of 41,810 participants, aged ≥ 18 years, were included. Depression status was assessed by standard methods derived from the World Mental Health Survey (WHH-CIDI). Undiagnosed depression was defined as a depressed person who did not report history of diagnosis/treatment for depression. Associations between depression/undiagnosed depression and chronic diseases, adjusting for country of residence, demographics and chronic diseases risk factors were assessed. Depression was detected in 2508 (6.0%) cases, from whom 2098 (87%) were undiagnosed. Diabetes (Odds ratio:1.47[95%CI:1.24,1.75]), arthritis (2.14[1.82,2.52]), asthma (3.36[2.73,4.14]), chronic lung disease (3.74[3.10,4.51]), angina (3.20[2.66,3.85]), and stroke (3.14[2.55,3.86]) were associated with depression (p-values < 0.001). Being older, female, underweight, and having lower education, and lower income were positively associated with depression. The estimated odds ratios were similar for undiagnosed depression. Cross-sectional design of study prevent us to determine whether depression followed exposures in time. About 12% of the participant did not have data for depression status and were excluded from the study. Most depression cases were undiagnosed. Depression/undiagnosed depression were strongly associated with chronic diseases stronger than what has been reported in developed countries.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.YPMED.2016.02.028
Abstract: Depression is widely considered to be an independent and robust predictor of Coronary Heart Disease (CHD), however is seldom considered in the context of formal risk assessment. We assessed whether the addition of depression to the Framingham Risk Equation (FRE) improved accuracy for predicting 10-year CHD in a s le of women. A prospective, longitudinal design comprising an age-stratified, population-based s le of Australian women collected between 1993 and 2011 (n=862). Clinical depressive disorder was assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-I/NP), using retrospective age-of-onset data. A composite measure of CHD included non-fatal myocardial infarction, unstable angina coronary intervention or cardiac death. Cox proportional-hazards regression models were conducted and overall accuracy assessed using area under receiver operating characteristic (ROC) curve analysis. ROC curve analyses revealed that the addition of baseline depression status to the FRE model improved its overall accuracy (AUC:0.77, Specificity:0.70, Sensitivity:0.75) when compared to the original FRE model (AUC:0.75, Specificity:0.73, Sensitivity:0.67). However, when calibrated against the original model, the predicted number of events generated by the augmented version marginally over-estimated the true number observed. The addition of a depression variable to the FRE equation improves the overall accuracy of the model for predicting 10-year CHD events in women, however may over-estimate the number of events that actually occur. This model now requires validation in larger s les as it could form a new CHD risk equation for women.
Publisher: Cambridge University Press (CUP)
Date: 23-12-2021
DOI: 10.1017/NEU.2021.44
Abstract: This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum s les were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults ( n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12 placebo 2.06 ± 1.35 pg/ml minocycline 1.77 ± 0.79 pg/ml p = 0.317), LBP (week 12 placebo 3.74 ± 0.95 µg/ml minocycline 3.93 ± 1.33 µg/ml p = 0.525) or BDNF (week 12 placebo 24.28 ± 6.69 ng/ml minocycline 26.56 ± 5.45 ng/ml p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA p = 0.021) and quality of life (Q-LES-Q-SF p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger s le size.
Publisher: SAGE Publications
Date: 16-09-2022
DOI: 10.1177/00048674221123481
Abstract: The objective of this study was to characterise the prevalence and/or severity of psychological distress (namely, depression and anxiety symptoms) in siblings of people with mental illness (MI) and to examine correlates of distress in siblings of people with MI. Studies comparing distress in in iduals with and without a sibling with MI were eligible. Studies reporting on correlates of distress in siblings were also eligible. A search of MEDLINE Complete, PsycINFO and Embase was conducted up until 17 March 2022. Fifteen studies comprising 2304 siblings and 2263 comparison in iduals were included. Meta-analyses indicated in iduals with a sibling with MI experience significantly greater depressive symptoms (Hedges’s g = 0.53, 95% CI = [0.32, 0.73], siblings n = 1962, comparison in iduals n = 2248) and anxiety symptoms (Hedges’s g = 0.40, 95% CI = [0.19, 0.61], siblings n = 653, comparison in iduals n = 533) than those without. The sibling relationship, siblings’ locus of control, interpersonal functioning and their appraisal of the impacts of MI were identified as important and potentially modifiable correlates. In iduals with a sibling with MI experience greater depressive and anxiety symptoms than those without and would likely benefit from support. Future studies are required to elucidate the mechanisms underlying distress in siblings.
Publisher: Informa UK Limited
Date: 03-08-2020
DOI: 10.1080/15622975.2018.1492734
Abstract: To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disorder (BD) on cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of differential expression in in iduals with BD. To use the GES to identify new drugs for BD using Connectivity Map (CMap).
Publisher: Korean College of Neuropsychopharmacology
Date: 31-08-2023
DOI: 10.9758/CPN.22.981
Publisher: Springer Science and Business Media LLC
Date: 09-02-2016
Publisher: IEEE
Date: 08-2016
Publisher: Springer Science and Business Media LLC
Date: 11-07-2013
Publisher: Wiley
Date: 09-2007
DOI: 10.1111/J.1399-5618.2007.00536.X
Abstract: Unipolar and bipolar depression differ neurobiologically and in clinical presentation. Existing depression rating instruments, used in bipolar depression, fail to capture the necessary phenomenological nuances, as they are based on and skewed towards the characteristics of unipolar depression. Both clinically and in research there is a growing need for a new observer-rated scale that is specifically designed to assess bipolar depression. An instrument reflecting the characteristics of bipolar depression was drafted by the authors, and administered to 122 participants aged 18-65 (44 males and 78 females) with a diagnosis of DSM-IV bipolar disorder, who were currently experiencing symptoms of depression. The Bipolar Depression Rating Scale (BDRS) was administered together with the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). The BDRS has strong internal consistency (Cronbach's alpha = 0.917), and robust correlation coefficients with the MADRS (r = 0.906) and HAM-D (r = 0.744), and the mixed subscale correlated with the YMRS (r = 0.757). Exploratory factor analysis showed a three-factor solution gave the best account of the data. These factors corresponded to depression (somatic), depression (psychological) and mixed symptom clusters. This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JAD.2015.11.048
Abstract: Previous research has demonstrated deficits in bone mineral density (BMD) among in iduals with depression. While reduced BMD is a known risk for fracture, a direct link between depression and fracture risk is yet to be confirmed. A population-based s le of women participating in the Geelong Osteoporosis Study was studied using both nested case-control and retrospective cohort study designs. A lifetime history of depression was identified using a semi-structured clinical interview (SCID-I/NP). Incident fractures were identified from radiological reports and BMD was measured at the femoral neck using dual energy absorptiometry. Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. Among 179 cases with incident fracture and 914 controls, depression was associated with increased odds of fracture (adjusted odds ratio (OR) 1.57, 95%CI 1.04-2.38) further adjustment for psychotropic medication use appeared to attenuate this association (adjusted OR 1.52, 95%CI 0.98-2.36). Among 165 women with a history of depression at baseline and 693 who had no history of depression, depression was associated with a 68% increased risk of incident fracture (adjusted hazard ratio (HR) 1.68, 95%CI 1.02-2.76), with further adjustment for psychotropic medication use also appearing to attenuate this association (adjusted HR 1.58, 95%CI 0.95-2.61). Potential limitations include recall bias, unrecognised confounding and generalizability. This study provides both cross-sectional and longitudinal evidence to suggest that clinical depression is a risk factor for radiologically-confirmed incident fracture, independent of a number of known risk factors. If there is indeed a clinically meaningful co-morbidity between mental and bone health, potentially worsened by psychotropic medications, the issue of screening at-risk populations needs to become a priority.
Publisher: Informa UK Limited
Date: 29-11-2019
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.JAD.2011.06.005
Abstract: Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 in iduals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (p<0.001). Improvements in functioning and quality of life were similarly evident. These open label data demonstrate a robust decrement in depression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.CPR.2017.01.002
Abstract: Current adjunctive psychosocial interventions for bipolar disorder (BD) aim to impact illness course via information sharing/skill development. This focus on clinical outcomes contrasts with the emergent recovery paradigm, which prioritises adaptation to serious mental illness and movement towards personally meaningful goals. The aim of this review is to encourage innovation in the psychological management of BD by considering three recovery-oriented trends in the literature. First, the importance of quality of life as a target of recovery-oriented clinical work is considered. Second, the recent staging approach to BD is described, and we outline implications for psychosocial interventions tailored to stage. Finally, we review evidence suggesting that mindfulness-based psychosocial interventions have potential across early, middle and late stages of BD. It is concluded that the humanistic emphasis of the recovery paradigm provides a timely stimulus for development of a next generation of psychosocial treatments for people with BD.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.PNPBP.2008.06.004
Abstract: Dietary factors influence BDNF in animal studies, but there is no comparable data in clinical populations. We examined the effect of a dietary intervention on BDNF serum levels in 67 DSM-IV schizophrenic outpatients (51 males and 16 females). Two groups were assessed in a cross-sectional study: one on a hypocaloric diet (HD) and the other not on a hypocaloric diet. Weight, height and BMI data were collected concurrently with 5-ml blood s ling of each subject. BDNF levels were measured with a sandwich-ELISA. The blood s le was obtained a minimum of one month after the exposure to dietary intervention. Serum BDNF levels were significantly higher in patients on the HD (p=0.023). Additional research examining the interaction among patterns of nutritional food behavior and underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.JPSYCHORES.2008.09.005
Abstract: Depression occurs commonly in coronary artery disease (CAD) and is associated with substantial disability. Modifiable cognitive determinants of depression in this population have not been identified. We investigated the impact of potentially modifiable illness beliefs about CAD on depressive symptomatology. We also examined the association between these beliefs and health-related quality of life (HRQOL) and socio-demographic variations in illness beliefs. A prospective study of 193 recently hospitalized CAD patients was conducted. Data were collected from medical records and by self-report 3 and 9 months post-discharge. Socio-demographic differences were analysed with independent s le t-tests. Predictive models were tested in a series of hierarchical linear regression equations that controlled for known clinical, psychosocial, and demographic correlates of outcome. Negative illness beliefs, particularly those associated with the consequences of CAD, were significantly predictive of higher levels of depressive symptomatology at 3 and 9 months. Positive illness perceptions were significantly associated with better HRQOL outcomes. Older and less socially advantaged patients demonstrated more negative illness beliefs. Illness beliefs are significantly associated with depressive symptomatology and HRQOL in CAD patients. These beliefs can be easily identified and constitute a meaningful and clinically accessible avenue for improving psychological morbidity and HRQOL in CAD patients. Older and more socially vulnerable patients may require heightened monitoring of their illness beliefs. Research needs to translate these and other predictive findings into interventions.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.JAD.2007.08.012
Abstract: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, observational study of participants with bipolar I or schizoaffective disorder examining clinical, functional, and economic outcomes associated with naturalistic treatment. Participants prescribed mood stabilisers were assessed using various measures, including the Young Mania Rating Scale (YMRS), 21-item Hamilton Depression Rating scale (HAMD21), Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), and the EuroQol instrument (EQ-5D). 240 participants were recruited from two sites. On average, participants were 41.8+/-12.7 years of age (mean+/-SD), 58.3% were female, and 73.3% had a diagnosis of bipolar I disorder at study entry. The majority of participants were moderately ill, with an average CGI-BP Overall score of 3.8+/-1.3. Most participants had subthreshold mania and depression symptoms, indicated by HAMD21 Total 13.4+/-8.6, CGI-BP Depression 3.2+/-1.3, YMRS Total 8.2+/-8.5 and CGI-BP Mania 3.0+/-1.6 average scores. For bipolar participants, 94.6% of hospitalisations for psychiatric treatment in the past 3 months were single admissions (vs. 65.2% for schizoaffective participants, p=.002). Bipolar participants rated their overall health state higher (EQ-5D scores: 68.2+/-18.8 vs. 61.6+/-22.7, p=.023), had a higher mean weekly wage ($500-$999, 21.3% vs. 6.3%), lower unemployment (22.2% vs. 48.4%), and higher romantic relationship status (47.1% vs. 26.6%). The observational design and small s le size may have limited the causal relationships and generalisability within the current findings. Participants were characterised by social and occupational dysfunction at entry, but schizoaffective participants appeared to be more severely affected. Effective treatment is required to address both clinical and functional impairment.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.JNEB.2019.03.006
Abstract: Poor diet is a leading cause of death and disease globally. This epidemic requires effective and accessible interventions to stop the increasing number of diet-related deaths and the health and economic impacts of diet-related disease. Online interventions provide flexibility and accessibility. With the ubiquitous use of smartphones, they can be intertwined with daily activities such as shopping and eating. The aim of this review is to determine what features and behavior change techniques employed in online dietary interventions for adult populations promoting dietary behavior change. The researchers conducted a systematic search of Cumulative Index of Nursing and Allied Health, Cochrane Library, Global Health, MEDLINE, PsychINFO, and psychological and behavioral sciences electronic bibliography databases, and specialist electronic health (e-health) journals from database inception to January, 2018. Studies were included if they were randomized controlled trials of online dietary interventions with active comparator conditions in adult populations, and with reported dietary change measures. A quality score was applied to each study calculated by a developed scoring system. The review analyzed intervention dietary change measures, attrition (nonuse and dropout), engagement (metrics and intensity of use), adherence (defined as compliance to the treatment protocol), behavior change techniques employed to achieve dietary change, and techniques employed in successful (those who achieved significant results in the targeted dietary behavior) vs unsuccessful interventions as reported by the studies. A total of 21 studies composed of a total of 7,455 adults and reporting on 19 different e-health interventions were included from 1,237 records. These studies targeted dietary change as measured by reduced energy intake (5) or changes in specific dietary components (15) and overall diet quality (4). Dietary change was a behavior target in general healthy populations (12) and for managing diseases such as obesity and cardiovascular disease (7), or for improving quality of life for those with chronic conditions (1). Improvements in dietary behavior were seen in 14 of the 19 interventions reported. The results suggest that online interventions can be successful in achieving dietary behavior change across a range of defined populations. However, disparate reporting of engagement and limited reporting of nonuse attrition rates limited the analysis of which behavior change techniques were most effective in achieving this change. The results of this review support the potential of online and smartphone dietary interventions as a method to achieve change in diet in defined populations. However, further work needs to be done in examining how users engage with interventions, and thus which behavior change techniques are most effective.
Publisher: SAGE Publications
Date: 31-08-2017
Abstract: While risk factors for depression are increasingly known, there is no widely utilised depression risk index. Our objective was to develop a method for a flexible, modular, Risk Index for Depression using structural equation models of key determinants identified from previous published research that blended machine-learning with traditional statistical techniques. Demographic, clinical and laboratory variables from the National Health and Nutrition Examination Study (2009–2010, N = 5546) were utilised. Data were split 50:50 into training:validation datasets. Generalised structural equation models, using logistic regression, were developed with a binary outcome depression measure (Patient Health Questionnaire-9 score ⩾ 10) and previously identified determinants of depression: demographics, lifestyle-environs, diet, biomarkers and somatic symptoms. Indicative goodness-of-fit statistics and Areas Under the Receiver Operator Characteristic Curves were calculated and probit regression checked model consistency. The generalised structural equation model was built from a systematic process. Relative importance of the depression determinants were diet (odds ratio: 4.09 95% confidence interval: [2.01, 8.35]), lifestyle-environs (odds ratio: 2.15 95% CI: [1.57, 2.94]), somatic symptoms (odds ratio: 2.10 95% CI: [1.58, 2.80]), demographics (odds ratio:1.46 95% CI: [0.72, 2.95]) and biomarkers (odds ratio:1.39 95% CI: [1.00, 1.93]). The relationships between demographics and lifestyle-environs and depression indicated a potential indirect path via somatic symptoms and biomarkers. The path from diet was direct to depression. The Areas under the Receiver Operator Characteristic Curves were good (logistic:training = 0.850, validation = 0.813 probit:training = 0.849, validation = 0.809). The novel Risk Index for Depression modular methodology developed has the flexibility to add/remove direct/indirect risk determinants paths to depression using a structural equation model on datasets that take account of a wide range of known risks. Risk Index for Depression shows promise for future clinical use by providing indications of main determinant(s) associated with a patient’s predisposition to depression and has the ability to be translated for the development of risk indices for other affective disorders
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: SAGE Publications
Date: 11-07-2017
Abstract: Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children’s Communication Checklist–Second Edition and the Repetitive Behavior Scale–Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. A total of 102 children were randomised into the study, and 98 (79 male, 19 female age range: 3.1–9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat s le. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.
Publisher: Royal College of Psychiatrists
Date: 05-2010
DOI: 10.1192/BJP.BP.108.058263
Abstract: Psychosocial interventions have the potential to enhance relapse prevention in bipolar disorder. To evaluate a manualised group-based intervention for people with bipolar disorder in a naturalistic setting. Eighty-four participants were randomised to receive the group-based intervention (a 12-week programme plus three booster sessions) or treatment as usual, and followed up with monthly telephone interviews (for 9 months post-intervention) and face-to-face interviews (at baseline, 3 months and 12 months). Participants who received the group-based intervention were significantly less likely to have a relapse of any type and spent less time unwell. There was a reduced rate of relapse in the treatment group for pooled relapses of any type (hazard ratio 0.43, 95% CI 0.20–0.95 t 343 = −2.09, P = 0.04). This study suggests that the group-based intervention reduces relapse risk in bipolar disorder.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2013
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.NEULET.2013.03.059
Abstract: To determine if oxidative stress and inflammation are linked with major depressive disorder, nicotine dependence and both disorders combined. This study comprised 150 smokers and 191 never smokers. The instruments were: a socio-demographic questionnaire, diagnoses of mood disorder and nicotine dependence according to DSM-IV, (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Laboratory assessments included: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde (MDA), total reactive antioxidant potential (TRAP), advanced oxidation protein products (AOPP), fibrinogen concentrations, homocysteine, erythrocytes sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were assayed from blood specimens. Statistically significant differences were found among depressed smokers who had more severe depressive symptoms, a higher risk of alcohol consumption, more suicide attempts, and more disability for work than non-depressed never smokers. Depressed smokers had significantly higher levels of NOx, fibrinogen, hs-CRP, AOPP, ESR and lower levels of TRAP compared to non-depressed never smokers. Depressed smokers had significant levels of oxidative stress and inflammatory biomarkers after adjusting for gender, age, years of education, disability for work, and laboratory measures. The levels of NOx, lipid hydroperoxides, AOPP, and fibrinogen were substantially higher, whereas levels of TRAP were lower in depressed smokers compared to non-depressed never smokers. (1) Depressed smokers exhibited altered concentrations of NOx, lipid hydroperoxides, AOPP, TRAP, and fibrinogen. (2) Depressed smokers were more unable to work, showed more severe depressive symptoms and attempted suicide more frequently.
Publisher: SAGE Publications
Date: 08-01-2020
Abstract: The drugs commonly used to treat bipolar disorder have limited efficacy and drug discovery is h ered by the paucity of knowledge of the pathophysiology of this disease. This study aims to explore the role of microRNAs in bipolar disorder and understand the molecular mechanisms of action of commonly used bipolar disorder drugs. The transcriptional effects of bipolar disorder drug combination (lithium, valproate, lamotrigine and quetiapine) in cultured human neuronal cells were studied using next generation sequencing. Differential expression of genes ( n=20) and microRNAs ( n=6) was assessed and the differentially expressed microRNAs were confirmed with TaqMan MicroRNA Assays. The expression of the differentially expressed microRNAs were inhibited to determine bipolar disorder drug effects on their target genes ( n=8). Independent s les t-test was used for normally distributed data and Kruskal-Wallis/Mann-Whitney U test was used for data not distributed normally. Significance levels were set at p .05. We found that bipolar disorder drugs tended to increase the expression of miR-128 and miR-378 ( p .05). Putative target genes of these microRNAs targeted pathways including those identified as “neuron projection development” and “axonogenesis”. Many of the target genes are inhibitors of neurite outgrowth and neurogenesis and were downregulated following bipolar disorder drug combination treatment (all p .05). The bipolar disorder drug combination tended to decrease the expression of the target genes ( NOVA1, GRIN3A, and VIM), however this effect could be reversed by the application of microRNA inhibitors. We conclude that at a transcriptional level, bipolar disorder drugs affect several genes in concert that would increase neurite outgrowth and neurogenesis and hence neural plasticity, and that this effect is mediated (at least in part) by modulation of the expression of these two key microRNAs.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.NEUBIOREV.2017.11.011
Abstract: Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways.
Publisher: Informa UK Limited
Date: 08-12-2020
Publisher: Frontiers Media SA
Date: 10-02-2022
DOI: 10.3389/FPSYT.2021.774858
Abstract: The COVID-19 pandemic has afforded the opportunity for some to improve lifestyle behaviours, while for others it has presented key challenges. Adverse changes in global lifestyle behaviours, including physical activity, sleep, and screen time can affect proximal mental health and in turn distal cardiovascular outcomes. We investigated differences in physical activity, sleep, and screen time in parents and children during early stages of the COVID-19 pandemic in Australia compared to pre-COVID-19 national data and estimated associations between these movement behaviours with parent and child mental health. Cross-sectional baseline data from the COVID-19 Pandemic Adjustment Study (CPAS N = 2,365) were compared to nationally representative pre-pandemic data from the Longitudinal Study of Australian Children (LSAC N = 9,438). Participants were parents of children aged ≤ 18 years, residing in Australia. Parents provided self-report measures of mental health, physical activity and sleep quality, and reported on child mental health, physical activity and screen time. Children in CPAS had significantly more sleep problems and more weekend screen time. Their parents had significantly poorer sleep quality, despite increased weekly physical activity. Children's sleep problems were significantly associated with increased mental health problems, after accounting for socioeconomic status, physical activity, and screen time. Poorer parent sleep quality and lower levels of physical activity were significantly associated with poorer mental health. Monitoring this cohort over time will be important to examine whether changes in movement behaviour are enduring or naturally improve with the easing of restrictions and whether these changes have lasting effects on either parent or child mental health, and in turn, future risk for CVD.
Publisher: SAGE Publications
Date: 21-03-2021
Abstract: The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymeth hetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the ‘Clinical Memorandum on Psychedelics’ recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymeth hetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to in iduals and detrimental to the field.
Publisher: American Psychological Association (APA)
Date: 2014
DOI: 10.1037/A0036543
Abstract: Although a great deal of literature supports the negative relationship between postinjury health outcomes and compensation, it has not fully examined the relative influence of the erse factors that underlie compensable status. In particular, this study sought to understand the relative influence that attributions of responsibility for accidents have on mental and physical health outcomes. Using a structural equation modeling approach, we assessed the strength of relationships between demographic and accident circumstance variables, and postinjury mental and physical health for 934 road-trauma survivors compensated under a single no-fault insurance system. Analysis of direct and indirect effects demonstrated that although a range of standard demographic and accident circumstance variables influenced health outcomes, by far the greatest effect was generated from perceptions of responsibility for the accident. People who reported lower levels of responsibility for their accident showed significantly poorer mental and physical health outcomes. Perceptions of responsibility for accidents are strongly associated with postaccident mental and physical health outcomes within compensable road trauma populations. Future studies should control for attributions of responsibility when assessing the effect of compensation, or any other variable, on health outcomes among injured populations. Mechanisms underlying the effect of attributions of responsibility on outcomes, particularly in relation to its association with self-blame, warrant further exploration.
Publisher: Springer Science and Business Media LLC
Date: 20-10-2020
Publisher: Wiley
Date: 25-10-2010
DOI: 10.1111/J.1365-2753.2010.01570.X
Abstract: A person's beliefs about their illness may contribute to recovery and prognosis. Some degree of acceptance of illness and its impact is necessary to integrate the presence of a chronic disorder into one's lifestyle and adhere to necessary components of illness management however, some in iduals can become 'stuck' and have difficulty adjusting out of the sick role. Inventories exist to measure illness cognitions, attitudes and behaviours as they relate to hypochondria and psychosomatic illness, but there is no extant measure of sick role inertia. We describe the psychometric properties of a new scale, the Illness Cognitions Scale (ICS), a metric of investment in the sick role. The ICS was administered to 97 in iduals with bipolar or schizoaffective disorder, and the psychometric properties of the scale measured. Dimensionality was assessed using Principal Components Analysis with Oblimin rotation. The scale has a strong internal consistency, with a Cronbach's alpha of 0.858. Results of a factor analysis suggested the presence of one main factor, with three other smaller, related sub-factors, capturing aspects of maladaptive illness beliefs. The ICS is a 17-item, internally validated scale measuring difficulty adjusting out of the sick role. The scale predominantly measures a single construct. Further research on external validity of the ICS is required as well as determination of the clinical significance and patient acceptability of the scale.
Publisher: Frontiers Media SA
Date: 19-07-2021
DOI: 10.3389/FNHUM.2021.644921
Abstract: The antidepressant actions of deep brain stimulation (DBS) are associated with progressive neuroadaptations within the mood network, modulated in part, by neurotrophic mechanisms. We investigated the antidepressant-like effects of chronic nucleus accumbens (NAc) DBS and its association with change in glycogen synthase kinase 3 (GSK3) and mammalian target of rapamycin (mTOR) expression in the infralimbic cortex (IL), and the dorsal (dHIP) and ventral (vHIP) subregions of the hippoc us of antidepressant resistant rats. Antidepressant resistance was induced via daily injection of adrenocorticotropic hormone (ACTH 100 μg/day 15 days) and confirmed by non-response to tricyclic antidepressant treatment (imipramine, 10 mg/kg). Portable microdevices provided continuous bilateral NAc DBS (130 Hz, 200 μA, 90 μs) for 7 days. A control sham electrode group was included, together with ACTH- and saline-treated control groups. Home cage monitoring, open field, sucrose preference, and, forced swim behavioral tests were performed. Post-mortem levels of GSK3 and mTOR, total and phosphorylated, were determined with Western blot. As previously reported, ACTH treatment blocked the immobility-reducing effects of imipramine in the forced swim test. In contrast, treatment with either active DBS or sham electrode placement in the NAc significantly reduced forced swim immobility time in ACTH-treated animals. This was associated with increased homecage activity in the DBS and sham groups relative to ACTH and saline groups, however, no differences in locomotor activity were observed in the open field test, nor were any group differences seen for sucrose consumption across groups. The antidepressant-like actions of NAc DBS and sham electrode placements were associated with an increase in levels of IL and vHIP phospho-GSK3β and phospho-mTOR, however, no differences in these protein levels were observed in the dHIP region. These data suggest that early response to electrode placement in the NAc, irrespective of whether active DBS or sham, has antidepressant-like effects in the ACTH-model of antidepressant resistance associated with distal upregulation of phospho-GSK3β and phospho-mTOR in the IL and vHIP regions of the mood network.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JAD.2014.09.035
Abstract: It remains uncertain whether schizoaffective disorder (SAD) is a discrete diagnostic entity, is a variant of either a psychotic mood disorder such as bipolar disorder (BDP) or schizophrenia (SCZ), or exists on a spectral continuum between these disorders. The present study examined whether SCZ, SAD, and BDP differed qualitatively on demographic and clinical variables based on a large Australian dataset. This study examined data from the Australian Survey of High Impact Psychosis (SHIP), in which 1469 of the 1825 participants in who had an ICD-10 diagnosis of SCZ (n=857), SAD (n=293), and BDP (n=319) were assessed across a broad range of variables. When compared to patients with SCZ, those with SAD reported more current delusional and thought disorder symptoms, a greater number of lifetime depression, mania, and positive symptoms, and fewer negative symptoms. Relative to the BPD group, the SAD group were younger, endorsed more current positive, delusional, and thought disorder symptoms, fewer lifetime mania symptoms, more lifetime psychotic, hallucination, and delusional symptoms, and recorded lower premorbid IQ scores. Compared to patients with BPD, those with SCZ were significantly younger, endorsed more current psychotic and hallucination symptoms, fewer lifetime depression and mania symptoms, more lifetime psychotic, hallucination, and delusional symptoms, reported more negative symptoms and had lower premorbid IQ and psychosocial functioning scores. Validated psychometric measures of psychotic or mood symptoms were not used. This pattern of results is consistent with the conceptualisation of a spectrum of disorders, ranging from BDP at one end, to SAD in the middle, and SCZ at the other end.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.PNPBP.2019.109708
Abstract: Major antioxidant responses to increased levels of inflammatory, oxidative and nitrosative stress (ONS) are detailed. In response to increasing levels of nitric oxide, S-nitrosylation of cysteine thiol groups leads to post-transcriptional modification of many cellular proteins and thereby regulates their activity and allows cellular adaptation to increased levels of ONS. S-nitrosylation inhibits the function of nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor-mediated signalling and the activity of several mitogen-activated protein kinases, while activating nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2 or NFE2L2) in turn, the redox-regulated activation of Nrf2 leads to increased levels and/or activity of key enzymes and transporter systems involved in the glutathione system. The Nrf2/Kelch-like ECH-associated protein-1 axis is associated with upregulation of NAD(P)H:quinone oxidoreductase 1, which in turn has anti-inflammatory effects. Increased Nrf2 transcriptional activity also leads to activation of haem oxygenase-1, which is associated with upregulation of bilirubin, biliverdin and biliverdin reductase as well as increased carbon monoxide signalling, anti-inflammatory and antioxidant activity. Associated transcriptional responses, which may be mediated by retrograde signalling owing to elevated hydrogen peroxide, include the unfolded protein response (UPR), mitohormesis and the mitochondrial UPR the UPR also results from increasing levels of mitochondrial and cytosolic reactive oxygen species and reactive nitrogen species leading to nitrosylation, glutathionylation, oxidation and nitration of crucial cysteine and tyrosine causing protein misfolding and the development of endoplasmic reticulum stress. It is shown how these mechanisms co-operate in forming a co-ordinated rapid and prolonged compensatory antioxidant response system.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JAD.2012.07.003
Abstract: In some in iduals, recovery from episodes of mental illness may be impeded by maladaptive illness beliefs and behaviors. For in iduals with chronic illness, acceptance of its presence and consequences is necessary to seek appropriate treatment, adjust their lifestyle, and adhere to recommended management strategies. Some have difficulty adjusting out of the sick role or develop a degree of illness investment. The Illness Cognitions Scale (ICS) is a 17-item validated scale that measures cognitive factors associated with the sick role. We conducted analyses to test the hypothesis that there may be an association between illness cognitions and clinical and functional measures. The ICS was administered to 89 participants at the final study visit of a 24-month observational study involving patients with bipolar I disorder or schizoaffective disorder. Higher scores on the ICS were correlated with more severe depression (p<0.0001), worse general health (p=0.0002), worse functioning (p=0.0001), and worse scores in psychosocial measures including the State Hope Scale (p=0.0082), the Social Provisions Scale (p=0.0054) and the Rosenberg Self-Esteem Scale (p=0.0025). Illness cognitions and behavior may be a neglected factor that could influence treatment outcomes in bipolar disorder. The ICS might be useful for identifying in iduals whose recovery may be facilitated by targeted psychological intervention that addresses these factors.
Publisher: MDPI AG
Date: 06-07-2022
DOI: 10.3390/IJMS23147508
Abstract: There is little understanding of the underlying molecular mechanism(s) involved in the clinical efficacy of antipsychotics for schizophrenia. This study integrated schizophrenia-associated transcriptional perturbations with antipsychotic-induced gene expression profiles to detect potentially relevant therapeutic targets shared by multiple antipsychotics. Human neuronal-like cells (NT2-N) were treated for 24 h with one of the following antipsychotic drugs: amisulpride, aripiprazole, clozapine, risperidone, or vehicle controls. Drug-induced gene expression patterns were compared to schizophrenia-associated transcriptional data in post-mortem brain tissues. Genes regulated by each of four antipsychotic drugs in the reverse direction to schizophrenia were identified as potential therapeutic-relevant genes. A total of 886 genes were reversely expressed between at least one drug treatment (versus vehicle) and schizophrenia (versus healthy control), in which 218 genes were commonly regulated by all four antipsychotic drugs. The most enriched biological pathways include Wnt signaling and action potential regulation. The protein-protein interaction (PPI) networks found two main clusters having schizophrenia expression quantitative trait loci (eQTL) genes such as PDCD10, ANK2, and AKT3, suggesting further investigation on these genes as potential novel treatment targets.
Publisher: American Medical Association (AMA)
Date: 10-2020
Publisher: Wiley
Date: 05-2009
DOI: 10.1111/J.1600-0447.2009.01382.X
Abstract: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of in idual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.COMPPSYCH.2013.12.019
Abstract: A self-report method seeking a binary response for assessing depression is a cost-effective and time-efficient way to obtain a psychiatric history, yet the reliability of this method is largely unknown. The aim of the study was to compare and assess the validity of two methods for identifying a past history of depression in a population-based study. This study examined data collected from 891 men and 1086 women participating in the Geelong Osteoporosis Study. Self-reports of depression were compared with results obtained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). Using the SCID-I/NP, 146 (16.4%) men and 285 (26.2%) women met criteria for a lifetime depression. Of those participants, 61.0% (n=263) self-reported a history of depression. The level of agreement between self-reporting depression and the SCID-I/NP depression module was reasonably high 61% sensitivity, 89.5% specificity and the overall level of agreement (kappa) was 0.5. Results may not be generalizable to other self-report instruments or be suitable for use in clinical s les. The SCID-I/NP remains the gold standard for identifying depression however, given the moderate level of agreement between the self-report questionnaire and SCID-I/NP in our current study, we conclude that simple self-report methods can be used to identify depression with some degree of confidence.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2019
DOI: 10.1007/S00394-019-02090-6
Abstract: Depression clinical trials are increasingly studying biomarkers to predict and monitor response to treatment. Assessment of biomarkers may reveal subsets of patients who are responsive to nutraceutical treatment, which may facilitate a personalized approach to treating depression. This is a post hoc analysis of an 8-week, double-blind, randomized, controlled trial (n = 158) investigating a combination nutraceutical comprising Omega-3 (EPA 1 g/DHA 656 mg), SAMe, zinc, 5-HTP, folinic acid, and co-factors versus placebo for the treatment of Major Depressive Disorder. The study explored levels of polyunsaturated fatty acids, folate, vitamin B12, zinc, homocysteine, and BDNF as possible predictors and correlates of response to nutraceutical supplementation. Concentrations of EPA and DHA in red cell membranes increased in response to treatment and were significantly correlated with a decrease in depressive symptoms during active treatment (p = 0.003 and p = 0.029 respectively). Higher baseline levels of omega-6 fatty acid also correlated with depression reduction in the active treatment group ( p = 0.011). No other biomarkers were associated with a lessening of depressive symptoms. Changes in fatty acid levels resulting from a nutraceutical combination containing EPA and DHA provide a response biomarker in treating depression.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2006
Abstract: Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian cancer patients, but its potential role in ovarian cancer metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary ovarian cancer cells, but not ovarian epithelial or borderline ovarian tumor cells, although these benign cells indeed respond to LPA in cell migration. We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators. G(i) protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), cytosolic phospholipase A(2) and urokinase type plasminogen activator (uPA) are required for LPA-induced cells invasion. TIMP3 may affect two independent downstream targets, vascular endothelial growth factor receptor and p38 MAPK. In vivo, LPA stimulates tumor metastasis in an orthotopic ovarian tumor model, which can be inhibited by a PI3K inhibitor, LY294002. In summary, LPA is likely a key component for promoting ovarian metastasis in vivo. LPA downregulates TIMP3, which may have targets other than metalloproteinases. Our in vivo metastasis mouse model is useful for studying the efficacy of therapeutic regimes of ovarian cancer.
Publisher: Cambridge University Press (CUP)
Date: 16-02-2017
DOI: 10.1017/S0033291717000022
Abstract: When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [ g = 0.508, 95% confidence interval (CI) 0.01–1.01, p = 0.047, I 2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses ( g = 0.734, 95% CI 0.00–1.49, p = 0.051). However, no effects of B vitamins were observed in in idual domains of positive and negative symptoms (both p 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness ( p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.
Publisher: Cambridge University Press (CUP)
Date: 15-04-2020
DOI: 10.1017/S1092852920001091
Abstract: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/13651500510029138
Abstract: Evidence from epidemiological studies has established that depression is a risk factor for the development of cardiovascular disease (CVD) and that the comorbidity of depression with pre-existing CVD worsens the prognosis for sufferers of CVD. Depression has also been associated with other behaviours that impact on CVD, such as medication non-compliance, and an unwillingness to adopt an exercise program, that reduce the likelihood of successful rehabilitation from CVD. Published literature on the current knowledge of the association between depression and CVD is reviewed in this paper.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/BDI.13124
Publisher: Wiley
Date: 18-07-2023
DOI: 10.1111/BDI.13366
Abstract: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized in iduals with BD in North America, Europe, and Australia. Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. In idual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns. This study included 10,351 in iduals from North America ( n = 3985), Europe ( n = 3822), and Australia ( n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60% vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2019
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.COMPPSYCH.2014.05.009
Abstract: The aim of this study was to evaluate the health-related quality of life (HRQoL) in bipolar type I (BD I) and schizoaffective (SQA) patients during a 2-year period in a naturalistic study. This study was based on the data generated by the Bipolar Comprehensive Outcome Study, a prospective, non-interventional, observational study of participants with BD I and SQA disorder. Mixed-Model Repeated Measures Analysis was used to analyze changes in the SF-36 and EQ-5D. Participants exhibited low health status at baseline with SF-36 mean scores of 46.7±10.5 and 36.9±12.9 (best imaginable health=100, normal population≈50) for physical and mental components, respectively. No significant differences were found between the ratings of the BD I and SQA patients on HRQoL. The SF-36 SMC improved significantly over 24 months although SPC scores remained consistent across the study. On the whole, the lowest SMC score was observed among the depressed patients (38.20), followed by the patients with a mixed state (39.01) and the manic patients (39.83). The observational design may have limited the causal relationships and the generalizability within the current findings. HRQoL was significantly impaired in all stages of BD and SQA when compared to the general population. The impairment of HRQoL was most pronounced in the depressed state, followed by the mixed state and then the manic state. The euthymic patients showed the least impairment. In addition, patients showed a global improvement in their mental health satisfaction over the 2 years follow up period.
Publisher: Korean College of Neuropsychopharmacology
Date: 28-12-2014
Publisher: Informa UK Limited
Date: 06-10-2022
DOI: 10.1080/15622975.2022.2112074
Abstract: The primary objectives of these international guidelines were to provide a global audience of clinicians with (a) a series of evidence-based recommendations for the provision of lifestyle-based mental health care in clinical practice for adults with Major Depressive Disorder (MDD) and (b) a series of implementation considerations that may be applicable across a range of settings. Recommendations and associated evidence-based gradings were based on a series of systematic literature searches of published research as well as the clinical expertise of taskforce members. The focus of the guidelines was eight lifestyle domains: physical activity and exercise, smoking cessation, work-directed interventions, mindfulness-based and stress management therapies, diet, sleep, loneliness and social support, and green space interaction. The following electronic bibliographic databases were searched for articles published prior to June 2020: PubMed, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), CINAHL, PsycINFO. Evidence grading was based on the level of evidence specific to MDD and risk of bias, in accordance with the World Federation of Societies for Biological Psychiatry criteria. Nine recommendations were formed. The recommendations with the highest ratings to improve MDD were the use of physical activity and exercise, relaxation techniques, work-directed interventions, sleep, and mindfulness-based therapies (Grade 2). Interventions related to diet and green space were recommended, but with a lower strength of evidence (Grade 3). Recommendations regarding smoking cessation and loneliness and social support were based on expert opinion. Key implementation considerations included the need for input from allied health professionals and support networks to implement this type of approach, the importance of partnering such recommendations with behaviour change support, and the need to deliver interventions using a biopsychosocial-cultural framework. Lifestyle-based interventions are recommended as a foundational component of mental health care in clinical practice for adults with Major Depressive Disorder, where other evidence-based therapies can be added or used in combination. The findings and recommendations of these guidelines support the need for further research to address existing gaps in efficacy and implementation research, especially for emerging lifestyle-based approaches (e.g. green space, loneliness and social support interventions) where data are limited. Further work is also needed to develop innovative approaches for delivery and models of care, and to support the training of health professionals regarding lifestyle-based mental health care.
Publisher: Frontiers Media SA
Date: 05-03-2019
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: IEEE
Date: 07-2013
Publisher: SAGE Publications
Date: 11-12-2020
Abstract: There is accumulating evidence that adjunctive treatment with We systematically reviewed Medline, EmCare, PsycINFO, Embase, CINAHL Complete, China Knowledge Resource Integrated Database and the Cochrane Clinical Trials online registry for randomised control trials of Seven studies, including Evidence supports the notion that
Publisher: Wiley
Date: 23-03-2021
DOI: 10.1111/ADD.15454
Abstract: Past research has found that young smokers are more likely to make quit attempts however, there are conflicting findings regarding age and quit success. This study examined the degree to which smoker age is related to making quit attempts and quit success. Ten waves of the International Tobacco Control Policy Cohort survey (ITC‐4C) collected between 2002 and 2014, with nine wave‐to‐wave transitions with predictors at the first wave predicting quit attempts and success by the next wave. Canada, the United States, the United Kingdom and Australia. Data from 15 874 smokers categorized into four age groups at baseline (18–24, 25–39, 40–54 and 55+ years). Age, quit attempts and success (defined as ≥ 30 days abstinence confirmed, if possible, on a third wave for recent attempts). Older smokers were more likely to smoke daily (χ 2 = 1557.86, r = 0.136, P 0.001) than younger smokers. Daily smokers were less likely to report quit attempts (38.1 versus 58.2%) and to achieve 30 days of abstinence (22.9 versus 34.3%) than non‐daily smokers. Older daily smokers were less likely to make quit attempts [0.61, confidence interval (CI) = 0.54–0.70, P 0.001], even after controlling for indicators of nicotine dependence, country, sex, education, income, relationship status and household composition, than younger smokers. Younger smokers ( 25) were more likely to succeed for at least 30 days of abstinence, but only when compared with those aged 40–54 (OR = 0.83, 95% CI = 0.68–0.99). However, when controlling for heaviness of smoking the age effect disappeared. Significant interactions with age were found between age and intention when predicting quit attempts, and age and heaviness of smoking when predicting quit success. An international cohort study indicates that young smokers are more likely to attempt to quit and appear to have similar levels of success in abstaining from smoking compared with older smokers when controlling for dependence. Quit success in all ages is most predicted by lower levels of nicotine dependence.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2016
Publisher: Wiley
Date: 16-05-2005
DOI: 10.1111/J.1440-1819.2005.01365.X
Abstract: Recent evidence suggests that the prevalence of bipolar disorder is as much as fivefold higher than previously believed, and may amount to nearly 5% of the population, making it almost as common as unipolar major depression. It is, therefore, not unrealistic to assume that primary care or family physicians will frequently encounter bipolar patients in their practice. Such patients may present with a depressive episode, for a variety of medical reasons, for longer-term maintenance after stabilization, and even with an acute manic episode. Whatever the reason, a working knowledge of current trends in the acute and longer-term management of bipolar disorder would be helpful to the primary care physician. In addition, an understanding of important side-effects and drug interactions that occur with drugs used to treat bipolar disorder, which may be encountered in the medical setting, are paramount. This paper will attempt to review existing and emerging therapies in bipolar disorder, as well as their common drug interactions and side-effects.
Publisher: EDITORA SCIENTIFIC
Date: 17-10-2016
Publisher: BMJ
Date: 04-2021
DOI: 10.1136/BMJOPEN-2020-044569
Abstract: Despite available pharmacological and psychological treatments, remission rates for bipolar disorder remain relatively low. Current research implicates the experience of childhood trauma as a potential moderator of poor treatment outcomes among in iduals with bipolar disorder. To date, the evidence reporting the influence of childhood trauma on the treatment outcomes of pharmacological and/or psychological interventions for adolescents and adults with bipolar disorder has not been systematically reviewed. MEDLINE Complete, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials will be searched to identify randomised and nonrandomised studies of pharmacological and/or psychological interventions for bipolar disorder, which also assessed childhood trauma. To be eligible for inclusion, studies must have been conducted with adolescents or adults (≥10 years). Data will be screened and extracted by two independent reviewers. The methodological quality of the included studies will be assessed with the Cochrane Collaboration’s Risk of Bias tool and the Newcastle-Ottawa Scale. If deemed viable, a meta-analysis will be conducted using a random effects model. Heterogeneity of evidence will be estimated with the I² statistics. This systematic review will use only previously published data. Therefore, ethical approval is not required. The results will be written in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, published in peer-reviewed journals and presented at relevant conferences. CRD42020201891.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.GENHOSPPSYCH.2019.10.001
Abstract: Psychological distress is associated with risk markers for cardiovascular disease, including increased arterial stiffness and high blood pressure, but it's unclear when these first manifest. This study aims to investigate the effect of psychosocial stress and depression on arterial stiffness and blood pressure in a cohort study of Australian children followed through to adolescence. Depression and psychosocial stress in 520 young people (265 boys M age = 11.6 y) were assessed via the Children's Depression Inventory and Children's Stress Questionnaire respectively. Carotid-femoral pulse wave velocity was assessed using applanation tonometry, with further assessments of supine brachial blood pressure and percent body fat (dual x-ray absorptiometry). All measures were repeated four years later at age 16-years. We found no cross-sectional or longitudinal evidence that children self-reporting higher levels of psychosocial stress or depressive symptoms had greater arterial stiffness. Children reporting an increase in depressive symptoms had an increase in diastolic blood pressure and mean arterial pressure over time. An effect was also evident for pulse pressure, where higher pulse pressure was found in children with lower psychosocial stress at baseline and in children self-reporting a decrease in stress between baseline and follow-up. Findings from the current study contribute to the scant paediatric literature but only provide limited support for any influence of psychological factors on blood pressure. Depressive symptoms in apparently healthy adolescents may exert some influence on later risk for cardiovascular disease via increases in diastolic blood pressure and mean arterial pressure, but these effects were small.
Publisher: SAGE Publications
Date: 11-07-2017
Abstract: We aimed to describe the prevalence and age distribution of personality disorders and their comorbidity with other psychiatric disorders in an age-stratified s le of Australian women aged ⩾25 years. In idual personality disorders (paranoid, schizoid, schizotypal, histrionic, narcissistic, borderline, antisocial, avoidant, dependent, obsessive-compulsive), lifetime mood, anxiety, eating and substance misuse disorders were diagnosed utilising validated semi-structured clinical interviews (Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition and Structured Clinical Interview for DSM-IV Axis II Personality Disorders). The prevalence of personality disorders and Clusters were determined from the study population ( n = 768), and standardised to the Australian population using the 2011 Australian Bureau of Statistics census data. Prevalence by age and the association with mood, anxiety, eating and substance misuse disorders was also examined. The overall prevalence of personality disorders in women was 21.8% (95% confidence interval [CI]: 18.7, 24.9). Cluster C personality disorders (17.5%, 95% CI: 16.0, 18.9) were more common than Cluster A (5.3%, 95% CI: 3.5, 7.0) and Cluster B personality disorders (3.2%, 95% CI: 1.8, 4.6). Of the in idual personality disorders, obsessive-compulsive (10.3%, 95% CI: 8.0, 12.6), avoidant (9.3%, 95% CI: 7.1, 11.5), paranoid (3.9%, 95% CI: 3.1, 4.7) and borderline (2.7%, 95% CI: 1.4, 4.0) were among the most prevalent. The prevalence of other personality disorders was low (⩽1.7%). Being younger (25–34 years) was predictive of having any personality disorder (odds ratio: 2.36, 95% CI: 1.18, 4.74), as was being middle-aged (odds ratio: 2.41, 95% CI: 1.23, 4.72). Among the strongest predictors of having any personality disorder was having a lifetime history of psychiatric disorders (odds ratio: 4.29, 95% CI: 2.90, 6.33). Mood and anxiety disorders were the most common comorbid lifetime psychiatric disorders. Approximately one in five women was identified with a personality disorder, emphasising that personality disorders are relatively common in the population. A more thorough understanding of the distribution of personality disorders and psychiatric comorbidity in the general population is crucial to assist allocation of health care resources to in iduals living with these disorders.
Publisher: SAGE Publications
Date: 03-06-2017
Abstract: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery–Asberg Depression Rating Scale (primary outcome), Clinical Global Impression–Improvement and Clinical Global Impression–Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery–Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression–Improvement score – effect size (95% confidence interval) = −0.62 [−1.8, −0.3], p = 0.02 Quality of Life Enjoyment and Satisfaction Questionnaire score – effect size (confidence interval) = −0.12 [0.0, 0.2], p 0.001 and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score – 0.79 [−4.5, −1.4], p 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [−1.7, −0.4], p = 0.017. While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.
Publisher: Wiley
Date: 18-03-2022
DOI: 10.1111/BDI.13198
Abstract: Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical s les with cross‐sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life‐story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.
Publisher: American Psychological Association (APA)
Date: 10-2021
DOI: 10.1037/CCP0000684
Publisher: Frontiers Media SA
Date: 13-03-2019
Publisher: SAGE Publications
Date: 2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JAD.2015.02.024
Abstract: People in the late stage of bipolar disorder (BD) experience elevated relapse rates and poorer quality of life (QoL) compared with those in the early stages. Existing psychological interventions also appear less effective in this group. To address this need, we developed a new online mindfulness-based intervention targeting quality of life (QoL) in late stage BD. Here, we report on an open pilot trial of ORBIT (online, recovery-focused, bipolar in idual therapy). Inclusion criteria were: self-reported primary diagnosis of BD, six or more episodes of BD, under the care of a medical practitioner, access to the internet, proficient in English, 18-65 years of age. Primary outcome was change (baseline - post-treatment) on the Brief QoL.BD (Michalak and Murray, 2010). Secondary outcomes were depression, anxiety, and stress measured on the DASS scales (Lovibond and Lovibond, 1993). Twenty-six people consented to participate (Age M=46.6 years, SD=12.9, and 75% female). Ten participants were lost to follow-up (38.5% attrition). Statistically significant improvement in QoL was found for the completers, t(15)=2.88, 95% CI:.89-5.98, p=.011, (Cohen׳s dz=.72, partial η(2)=.36), and the intent-to-treat s le t(25)=2.65, 95% CI:.47-3.76, (Cohen׳s dz=.52 partial η(2)=.22). A non-significant trend towards improvement was found on the DASS anxiety scale (p=.06) in both completer and intent-to-treat s les, but change on depression and stress did not approach significance. This was an open trial with no comparison group, so measured improvements may not be due to specific elements of the intervention. Structured diagnostic assessments were not conducted, and interpretation of effectiveness was limited by substantial attrition. Online delivery of mindfulness-based psychological therapy for late stage BD appears feasible and effective, and ORBIT warrants full development. Modifications suggested by the pilot study include increasing the 3 weeks duration of the intervention, adding cautions about the impact of extended meditations, and addition of coaching support/monitoring to optimise engagement.
Publisher: EDITORA SCIENTIFIC
Date: 09-2017
Publisher: SAGE Publications
Date: 29-05-2014
Publisher: Wiley
Date: 20-06-2013
DOI: 10.1111/BDI.12099
Abstract: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists in idualized care. Staging places an in idual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and in idualized intervention approaches. We provide a narrative review of the relevant information. In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk in iduals and early intervention strategies for newly diagnosed in iduals, and the tailored implementation of treatments according to the stage of illness. The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a ersity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible.
Publisher: JMIR Publications Inc.
Date: 11-2022
DOI: 10.2196/36496
Abstract: Internet-delivered psychosocial interventions can overcome barriers to face-to-face psychosocial care, but limited evidence supports their cost-effectiveness for people with bipolar disorders (BDs). This study aimed to conduct within-trial cost-effectiveness and cost-utility analyses of an internet-based intervention for people with BD, MoodSwings 2.0, from an Australian health sector perspective. MoodSwings 2.0 included an economic evaluation alongside an international, parallel, and in idually stratified randomized controlled trial comparing an internet-based discussion forum (control group 1), a discussion forum plus internet-based psychoeducation (group 2), and a discussion forum plus psychoeducation and cognitive behavioral tools (group 3). The trial enrolled adults (aged 21 to 65 years) with a diagnosis of BD assessed by telephone using a structured clinical interview. Health sector costs included intervention delivery and additional health care resources used by participants over the 12-month trial follow-up. Outcomes included depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS the trial primary outcome) and quality-adjusted life years (QALYs) calculated using the short-form 6-dimension instrument derived from the 12-item version of the short-form health survey. Average incremental cost-effectiveness (cost per MADRS score) and cost-utility (cost per QALY) ratios were calculated using estimated mean differences between intervention and control groups from linear mixed effects models in the base case. In total, 304 participants were randomized. Average health sector cost was lowest for group 2 (Aus $9431, SD Aus $8540 Aus $1=US $0.7058) compared with the control group (Aus $15,175, SD Aus $17,206) and group 3 (Aus $15,518, SD Aus $30,523), but none was statistically significantly different. The average QALYs were not significantly different among the groups (group 1: 0.627, SD 0.062 group 2: 0.618, SD 0.094 and group 3: 0.622, SD 0.087). The MADRS scores were previously shown to differ significantly between group 2 and the control group at all follow-up time points (P .05). Group 2 was dominant (lower costs and greater effects) compared with the control group for average incremental cost per point decrease in MADRS score over 12 months (95% CI dominated to Aus $331). Average cost per point change in MADRS score for group 3 versus the control group was dominant (95% CI dominant to Aus $22,585). Group 2 was dominant (95% CI Aus $43,000 to dominant) over the control group based on lower average health sector cost and average QALY benefit of 0.012 (95% CI –0.009 to 0.033). Group 3, compared with the control group, had an average incremental cost-effectiveness ratio of dominant (95% CI dominated to Aus $19,978). Web-based psychoeducation through MoodSwings 2.0 has the potential to be a cost-effective intervention for people with BD. Additional research is needed to understand the lack of effectiveness for the addition of cognitive behavioral tools with the group 3 intervention.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2014
Publisher: SAGE Publications
Date: 21-07-2023
DOI: 10.1177/00048674231187312
Abstract: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD ( n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of in idual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in erse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: SAGE Publications
Date: 23-12-2021
Abstract: Garcinia mangostana Linn. (“mangosteen”) pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia. People diagnosed with schizophrenia or schizoaffective disorder ( Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019. Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74) data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks. Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder.
Publisher: AMPCo
Date: 02-2013
DOI: 10.5694/MJA12.11740
Publisher: Elsevier BV
Date: 04-2015
Publisher: Korean College of Neuropsychopharmacology
Date: 28-08-2023
DOI: 10.9758/CPN.23.1098
Publisher: Research Square Platform LLC
Date: 24-11-2020
DOI: 10.21203/RS.3.RS-48845/V2
Abstract: Background: Anticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based s le of men and women. Methods: Data from 926 men (24-73yr) and 1070 women (21-94yr) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm 2 ) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders. Results: Seventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. In women, BMD tended to be lower at the hip compared to non-users as with the bone quality measure, BUA. No significant associations were observed at the spine or the other bone quality measures, SOS and SI. Conclusion: Our data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.
Publisher: Elsevier BV
Date: 05-2015
Publisher: JMIR Publications Inc.
Date: 08-10-2020
Abstract: nline interventions can be a cost-effective and efficient way to deliver programs to large numbers of people regardless of geographic location. However, attrition in web-based interventions is often an issue. Developing ways to keep participants engaged is important for ensuring validity and limiting potential biases. We developed a web-based dietary intervention as part of The My Food & Mood study which aimed to optimize ways to engage participants with low mood or depressive symptoms to promote dietary behavior change. Different versions of the My Food & Mood program were tested during optimization. Iterations were developed based on user feedback and usage analysis. he purpose of this study was to compare engagement and nonusage attrition across 4 program iterations—which differed by platform format, delivery mode, and activity type—to create an optimized version. ach program version contained modular videos with key activities with respect to implementing behavior change techniques of equivalent levels of required participation and length: version 1.0, desktop program and smartphone app version 2.1, desktop or smartphone program version 2.2, desktop program and version 3.0, smartphone app. Adults with PHQ-8 scores of 5 or greater were recruited online and assigned to 1 of the 4 versions. Participants were asked to use the program for 8 weeks and complete measures at weeks 4 and 8. Engagement data were collected from the web-based platform system logs and customized reports. Cox regression survival analysis examined nonusage attrition and Kruskal-Wallis tests compared engagement across each cohort. total of 614 adults participated. Kruskal-Wallis tests showed significant differences across the 4 cohorts in all engagement measures. The smartphone app (version 3.0) had the greatest engagement as measured by weeks engaged, total usage time, total time key activities, number of active sessions, percentage of activities completed against protocol, goals completed, and percentage of videos watched. Cox regression multivariate survival analysis showed referral from a health practitioner (hazard ratio [HR] 0.344, i P /i =.001) and greater proficiency with computers (HR 0.796, i P /i =.049) reduced the risk of nonusage attrition. Computer confidence was associated with an increased risk of nonusage attrition. y Food & Mood version 3.0, a dietary intervention delivered via smartphone app with self-monitoring tools for diet quality and mood monitoring, was the version with greatest engagement in a population with low mood or depression. The iterative design techniques employed and analysis of feedback from participants resulted in a program that achieved lower rates of nonusage attrition and higher rates of intensity of use.
Publisher: Cambridge University Press (CUP)
Date: 2016
DOI: 10.1016/J.EURPSY.2015.09.460
Abstract: Cognitive deficits have been reported during the early stages of bipolar disorder however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
Publisher: Wiley
Date: 05-10-2020
DOI: 10.1002/HBM.25212
Abstract: Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The s le included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia ( n = 183), affective psychosis ( n = 39), or other psychotic disorders ( n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient s le, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippoc al ( d = −0.25) volumes, and higher caudate ( d = 0.25) and pallidum ( d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia ( d = −0.34) and affective psychosis ( d = −0.42), and early‐onset schizophrenia showed lower hippoc al ( d = −0.24) and higher pallidum ( d = 0.29) volumes. Patients who were currently treated with antipsychotic medication ( n = 193) had significantly lower intracranial volume ( d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early‐onset psychosis.
Publisher: Springer Science and Business Media LLC
Date: 2007
DOI: 10.2165/00023210-200721020-00003
Abstract: Clozapine is an important antipsychotic agent that has a unique profile of clinical benefits, but that has also been associated with several serious and potentially life-threatening safety concerns. In order to minimise the impact of haematological adverse events, health professionals treating patients with clozapine are currently required to register their patients on a centrally administered data network and to conform to strict protocols. The consensus statement documented in this article extends existing protocols by recommending monitoring of patients treated with clozapine for additional adverse effects during treatment. This consensus statement reflects the current practice at five major public psychiatric hospitals in Victoria, Australia, for the monitoring and management of clozapine-related adverse events, and has been implemented at these sites because of emerging safety concerns associating clozapine with cardiovascular and metabolic adverse effects.
Publisher: Public Library of Science (PLoS)
Date: 10-11-2014
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAD.2019.01.054
Abstract: Data from the World Health Organization Study on global AGEing and adult health (SAGE) were used to estimate the prevalence of depression in older adults in six low- and middle-income countries (LMICs), namely China, Ghana, India, Mexico, the Russian Federation, and South Africa, and to examine the relationship between demographic and lifestyle characteristics and depression. A total of 33,421 participants aged ≥ 50 years were included. A set of diagnostic questions from the World Mental Health Survey was used within SAGE to define depression. The crude population prevalence of depression was 7.4% [95%CI: 6.5%-8.3%] ranging from 1.5% in China to 15.2% in India. It was higher in females 8.6% [7.6%-9.6%] compared to males 6.1% [5.0%-7.2%]. The age-standardized prevalence of depression was 7.8% [6.3%-9.6%] in pooled data, 8.9% [6.9%-11.1%] in females and 6.6% [4.6%-9.0%] in males. Greater fruit (0.89[0.84-0.93]) and vegetable intake (0.94 [0.89-1.00]) was associated with a lower prevalence of depression. Furthermore, those who were older, female, underweight, and with lower education and lower wealth, had higher prevalence of depression. The cross-sectional design of this study precluded conclusions on causality. In nationally-representative s les of older adults in six LMICs, an average of one in every 13 participants suffered from depression. The prevalence of depression varied considerably between countries, sexes, and with wealth and educational disadvantage. Increased fruit and vegetable intake appeared to co-occur with significantly lower rates of depression, suggesting diet as a modifiable factor for addressing depression burden.
Publisher: American Psychological Association (APA)
Date: 2014
DOI: 10.1037/REP0000012
Abstract: Perceptions surrounding the underlying causes of accidents and injuries may be a key mechanism influencing postaccident health and functional outcomes among people injured in road crashes. In particular, attributions of responsibility may influence rates of postcrash depressive symptomatology and return-to-work. We studied a large s le of people injured in motor vehicle crashes who were working at their time of accident and needed to take time off as a result of their injuries. Interviews took place at 2 time points, 12 months apart (T1: n = 1,024, T2: n = 303). Comparisons were made between participants' levels of depressive symptoms and rates of return to work based on their assessment of responsibility for their accident. People who did not attribute responsibility to themselves for their accident were 3 times more likely to exhibit symptoms of depression at follow-up than those who attributed responsibility to themselves. People with depressive symptoms were 3.5 times less likely to have returned to work. The effect of attributions of responsibility for accidents on return to work was mediated by the presence of depressive symptoms. Functional and psychological recovery from road trauma is closely associated with the assessment of responsibility for accidents. Findings are discussed in light of established posttrauma cognitive theories, the potential explanatory power of broader, more socially oriented models, and the changing nature of road trauma populations.
Publisher: SAGE Publications
Date: 14-08-2020
Abstract: Early learning services and schools provide unique settings for mental health promotion and early intervention due to the potential for population-level dosage and reach in terms of reducing multiple risk factors and enabling protective factors among young people. Educators play a key role in supporting children and young people’s experiences of, and access to mental health promotion opportunities, and hold unparalleled opportunity in terms of creating mental health–promoting learning environments. In 2018, the Australian National Mental Health in Education Initiative, Be You, was launched. Be You is a multi-million-dollar Australian government–supported initiative, freely available to all 24,000 early learning services, primary and secondary schools throughout Australia. The potential for subsequent population reach is proposed to potentially exceed that of any mental health promotion initiative for children and young people previously observed in Australia. Be You aims to foster mentally healthy learning communities across Australia through building capacity among educators to embed mental health promotion strategies. The Initiative was developed based on a review and integration of previous national mental health promotion frameworks, with an overall alignment to existing state and territory education, social and emotional well-being frameworks, and the Australian Curriculum. In delivering facilitated support from specialised consultants to early learning services and schools participating in the initiative, Be You draws on professional learning principles designed to build capacity in educators and educational systems relating to mental health promotion. It uses an updated, multi-module online platform providing interactive, evidence-based resources. This paper presents the Be You framework, describes the evidence sources used to inform the underlying principles and objectives, discusses the specific components that form the initiative, details the professional learning modules and content, and discusses potential implications for population mental health and prevention efforts.
Publisher: SAGE Publications
Date: 12-05-2023
DOI: 10.1177/10398562231174691
Abstract: The field of early psychosis has undergone considerable expansion over the last few decades and has a strong evidence base of effectiveness. Like all areas of healthcare, however, early psychosis services need to more consistently deliver higher quality care to achieve better outcomes for patients and families. A national clinical research infrastructure is urgently required to enable the sector to deliver the highest quality care and expand and translate evidence more quickly and efficiently. This paper describes the establishment of the Australian Early Psychosis Collaborative Consortium (AEPCC) that aims to achieve this. AEPCC is the first of its kind in Australia (and internationally). It will deliver the required clinical research infrastructure through the implementation of a clinical quality registry, clinical trials and translation network, and lived experience network. AEPCC will provide a critical resource to better understand the state of early psychosis care, and trial new interventions on a scale that has not previously been possible in Australia.
Publisher: Wiley
Date: 19-07-2019
DOI: 10.1111/EIP.12716
Abstract: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans. Ninety participants have been recruited and baseline characteristics are presented. Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.
Publisher: Wiley
Date: 08-01-2012
DOI: 10.1111/J.1751-7893.2011.00336.X
Abstract: There is a scarce literature describing psychological interventions for a young, first-episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population. The study was an open-label design, drawn from a larger pharmacotherapy trial. All participants in the pharmacotherapy trial were offered a manualized psychological intervention in addition to case management. Inclusion in the psychotherapy group was based on participant's choice, and on completion of four or more of the eight modules offered. All clinical files were audited to ensure accuracy of group allocation. Forty young people aged 15 to 25 years old who had experienced a manic episode with psychotic features were recruited into the study, with 20 people in the combined treatment as usual plus psychotherapy group (P+TAU), and an equal number of matched control participants who received treatment as usual (TAU) within the same service. All participants were prescribed antipsychotic and mood-stabilizing medication. Symptomatic, functional and relapse measures were taken both at baseline and at 18-month follow-up. Manic symptoms improved significantly for both groups, with no differences between groups. Depression scores and overall symptom severity were significantly lower in the P + TAU group. No differences were evident between groups with regard to numbers or type of relapse. The P + TAU group had significantly better social and occupational functioning after 18 months. This study suggests that a manualized psychological intervention targeted to a first-episode population can be effective in reducing depression and overall symptom severity, and can improve functional outcome following a first episode of psychotic mania.
Publisher: Wiley
Date: 19-10-2020
DOI: 10.1002/HBM.25249
Abstract: The hippoc us consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta‐Analysis Bipolar Disorder workinggroup, study hippoc al subfield volumetry in BD. T1‐weighted magnetic resonance imaging scans from 4,698 in iduals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed‐effects models and mega‐analysis to investigate differences in hippoc al subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippoc us (Cohen's d = −0.20), cornu ammonis (CA)1 ( d = −0.18), CA2/3 ( d = −0.11), CA4 ( d = −0.19), molecular layer ( d = −0.21), granule cell layer of dentate gyrus ( d = −0.21), hippoc al tail ( d = −0.10), subiculum ( d = −0.15), presubiculum ( d = −0.18), and hippoc al amygdala transition area ( d = −0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non‐users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippoc al subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.
Publisher: Springer Science and Business Media LLC
Date: 10-07-2013
Abstract: Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia. In iduals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score 53 were compared to 53 healthy in iduals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals 50 ms different from preceding interval (pNN50). Pearson’s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)). The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group ( P .05). The mean value of the LF in the depression group was higher than the in control group ( P .05). Furthermore the ratio of LF/HF was higher among the depression group than the control group ( P .05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group ( P .05), particularly supraventricular arrhythmias. Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. In iduals with depression appear to be susceptible to premature atrial and/or ventricular disease.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JAD.2015.03.025
Abstract: Identification of earlier stages of Bipolar Disorder (BD), even prior to the first manic episode, may help develop interventions to prevent or delay the onset of BD. However, reliable and valid instruments are necessary to ascertain such earlier stages of BD. The aim of the current review was to identify instruments that had predictive validity and utility for BD for use in early intervention (EI) settings for the prevention of BD. We undertook a systematic examination of studies that examined participants without BD I or II at baseline and prospectively explored the predictive abilities of instruments for BD onset over a period of 6 months or more. The instruments and the studies were rated with respect to their relative validity and utility predicting onset of BD for prevention or early intervention. Odds ratios and area under the curve (AUC) values were derived when not reported. Six studies were included, identifying five instruments that examined sub-threshold symptoms, family history, temperament and behavioral regulation. Though none of the identified instruments had been examined in high-quality replicated studies for predicting BD, two instruments, namely the Child Behavioral Checklist - Pediatric BD phenotype (CBCL-PBD) and the General Behavioral Inventory - Revised (GBI-R), had greater levels of validity and utility. Non-inclusion of studies and instruments that incidentally identified BD on follow-up limited the breadth of the review. Instruments that test domains such as subthreshold symptoms, behavioral regulation, family history, and temperament hold promise in predicting BD onset.
Publisher: Informa UK Limited
Date: 18-06-2022
DOI: 10.1080/15622975.2021.1925152
Abstract: This study examined cognition-immune interactions, specifically executive function, working memory, peripheral levels of tumour necrosis factor-alpha (TNF-α), and soluble tumour necrosis factor receptors-1 and -2 (sTNFR1 and 2) levels in bipolar disorder (BD) patients in comparison with controls. Thirty-one BD participants and twenty-seven controls participated in the study. The neurocognitive assessment was performed through three of CogState Research Battery BD presented a significantly worse performance in the working memory task ( TNF-α and its receptors might be an important variable in cognitive impairment in BD. Future studies might focus on the development of anti-inflammatory therapeutic targets for cognitive dysfunction in BD.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.PSYNEUEN.2014.02.004
Abstract: Emerging research has suggested that hormone treatments such as selective oestrogen receptor modulators (SERMs) or progestins may be useful in the treatment of mania. The current pilot study compared the use of the SERM tamoxifen and the progestin medroxyprogesterone acetate (MPA), as an adjunct to mood stabiliser medications, for the treatment of mania symptoms in 51 women in a 28-day double blind, placebo controlled study. The primary outcome was the change between baseline and day 28 mania scores as measured by the Clinician Administered Rating Scale for Mania (CARS-M). Adjunctive MPA treatment provided greater and more rapid improvement in mania symptoms compared with adjunctive placebo and tamoxifen treatment. Adjunctive therapy with MPA may be a potentially useful new treatment for persistent mania, leading to a greater and more rapid resolution of symptoms compared with mood stabiliser treatment alone.
Publisher: Cambridge University Press (CUP)
Date: 2016
DOI: 10.1016/J.EURPSY.2016.02.003
Abstract: Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD. This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges’ adjusted g using random effects. Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania ( g = −0.99, 95% CI −2.43 to 0.43, P = 0.171), in depression ( g = 0.17, 95% CI −0.45 to 0.79, P = 0.584), or in euthymia ( g = 0.03, 95% CI −0.39 to 0.46, P = 0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the in iduals, the greater the difference in leptin levels between BD and controls and the higher the BMI, the greater the difference in leptin levels between BD and controls. Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.PNPBP.2011.02.011
Abstract: Obsessive-compulsive disorder (OCD) is a debilitating mental illness which has a significant impact on quality of life. First-line SSRI treatments for OCD typically are of limited benefit to only 40-60% of patients, and are associated with a range of adverse side effects. Current preclinical research investigating nutraceuticals (natural products) for OCD, reveals encouraging novel activity in modulating key pathways suggested to be involved in the pathogenesis of OCD (glutamatergic and serotonergic pathway dysregulation). Emerging clinical evidence also appears to tentatively support certain nutrients and plant-based interventions with known active constituents which modulate these pathways: N-acetlycysteine, myo-inositol, glycine, and milk thistle (Silybum marianum). The serotonin precursor tryptophan is unlikely to be of use in treating OCD while 5-HTP may possibly be a more effective precursor strategy. However, there is currently no clinical evidence to test the efficacy of either of these substances. Currently the balance of clinical evidence does not support the use of St. John's wort (Hypericum perforatum) in OCD. While clinical research in this area is in its infancy, further research into nutraceuticals is warranted in light of the promising preclinical data regarding their mechanisms of action and their favourable side effect profiles in comparison to current SSRI treatments. It is recommended that future clinical trials of nutraceutical treatments for OCD utilize randomized placebo-controlled study designs and considerably larger s le sizes in order to properly test for efficacy.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JAD.2018.08.041
Abstract: There is evidence that substance use disorders and other mental disorders may have shared biological mechanisms. However, the neurobiological basis of this comorbidity remains only partially explained. This review describes the historical evolution of the dual disorders concept and approach, and reviews the existing literature on neurobiological findings specifically regarding comorbid substance use and mood disorders. Searches were conducted using PubMed and Scopus in December 2017. A Boolean search was performed using combinations of "dual diagnosis" or "dual disorder" or "depression" or "bipolar" or "affective disorder" or "mood disorder" and "substance use" or "substance abuse" and "neurobiology" or "functional neuroimaging" or "genetics" or "neurotransmitters" or "neuroendocrinology" in the title or abstract, or as keywords, using no language restriction. 32 studies met the inclusion criteria. We found robust evidence for involvement of the neurotransmitters dopamine, GABA and glutamate and their receptors, as well as by the central corticotrophin-releasing hormone, hypothalamic-pituitary-adrenal axis activation, oxidative stress and inflammation. Recent studies focusing on neuroimaging and genetics have not shown consistent results. Only two search tools were used most identified studies excluded the population of interest (comorbid mood and substance abuse disorders). The neurobiological relevance for the occurrence of comorbid mood and substance abuse disorders has not been fully elucidated. Considering the high levels of in iduals who experience comorbidity in these areas as well as the negative associated outcomes, this is clearly an area that requires further in-depth investigation. Furthermore, findings from this area can help to inform drug abuse prevention and intervention efforts, and especially how they relate to populations with psychiatric symptoms.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 09-2017
Publisher: Cambridge University Press (CUP)
Date: 06-2006
DOI: 10.1111/J.1601-5215.2006.00147.X
Abstract: Since bipolar affective disorder has been recorded, clinicians treating patients with this disorder have noted the cyclic nature of episodes, particularly an increase in mania in the spring and summer months and depression during winter. The aim of this study was to investigate seasonality in symptom onset and service admissions over a period of 10 years in a group of patients ( n = 359) with first-episode (FE) mania ( n = 133), FE schizoaffective disorder ( n = 49) and FE schizophrenia ( n = 177). Patients were recruited if they were between 15 and 28 years of age and if they resided in the geographical mental health service catchment area. The number of patients experiencing symptom onset and service admission over each month and season was recorded. In terms of seasonality of time of service admission, the results indicate a high overall seasonality (particularly in men), which was observed in both the schizoaffective and the bipolar groups. In terms of seasonality of symptom onset, the results indicate that seasonality remains in the male bipolar group, but other groups have no seasonal trend. This provides further evidence that systems mediating the entrainment of biological rhythms to the environment may be more pronounced in BPAD than in schizoaffective disorder and schizophrenia. These results may help facilitate the preparedness of mental heath services for patients at different times of the year.
Publisher: Cambridge University Press (CUP)
Date: 08-09-2023
DOI: 10.1017/NEU.2023.45
Publisher: Cold Spring Harbor Laboratory
Date: 03-05-2022
DOI: 10.1101/2022.05.02.22274560
Abstract: Recent data indicates high prevalence of post-traumatic stress disorder (PTSD) in bipolar disorder (BD). PTSD may play a role in poor treatment outcomes and quality of life for people with BD. Despite this, few studies have examined the pharmacological treatment interventions and outcomes for this comorbidity. This systematic review will bring together currently available evidence regarding the impact of comorbid PTSD on pharmacological treatment outcomes in adults with BD. A systematic search of Embase, MEDLINE Complete, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be conducted to identify randomised and non-randomised studies of pharmacological interventions for adults with diagnosed bipolar disorder and PTSD. Data will be screened and extracted by two independent reviewers. Literature will be searched from the creation of the databases until April 1 2021. Risk of bias will be assessed using the Newcastle-Ottawa Scale and the Cochrane Collaborations Risk of Bias tool. A meta-analysis will be conducted if sufficient evidence is identified in the systematic review. The meta-analysis will employ a random-effects model and be evaluated using the I 2 statistic. This review and meta-analysis will be the first to systematically explore and integrate the available evidence on the impact of PTSD on pharmacological treatments and outcome in those with BD. The results and outcomes of this systematic review will provide directions for future research and be published in relevant scientific journals and presented at research conferences. The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42020182540).
Publisher: Wiley
Date: 11-11-2014
DOI: 10.1111/NHS.12095
Publisher: Oxford University Press (OUP)
Date: 21-01-2008
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.MEDENGPHY.2015.07.003
Abstract: This paper presents the development of an energy harvesting circuit for use with a head-mountable deep brain stimulation (DBS) device. It consists of a circular planar inverted-F antenna (PIFA) and a Schottky diode-based Cockcroft-Walton 4-voltage rectifier. The PIFA has the volume of π × 10(2) × 1.5 mm(3), resonance frequency of 915 MHz, and bandwidth of 16 MHz (909-925 MHz) at a return loss of -10 dB. The rectifier offers maximum efficiency of 78% for the input power of -5 dBm at a 5 kΩ load resistance. The developed rectenna operates efficiently at 915 MHz for the input power within -15 dBm to +5 dBm. For operating a DBS device, the DC voltage of 2 V is recorded from the rectenna terminal at a distance of 55 cm away from a 26.77 dBm transmitter in free space. An in-vitro test of the DBS device is presented.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Public Library of Science (PLoS)
Date: 21-09-2011
Publisher: Cambridge University Press (CUP)
Date: 30-05-2018
DOI: 10.1016/J.EURPSY.2018.05.006
Abstract: Concordant with an increased emphasis on consumer engagement, the Patient Global Impression Scale of Improvement (PGI-I) is commonly used as an outcome measure in studies evaluating the efficacy of treatments in medical and psychiatric conditions with subjective symptom domains. The current study evaluated the agreement between PGI-I and Clinician Global Impression Scale of Improvement (CGI-I) ratings and convergent validity of PGI-I among in iduals with bipolar or major depressive disorders. Data were derived from three double-blind, placebo-controlled, multicentre studies conducted from 2007 to 2015 among adult in iduals (N = 472). Clinicians were asked to rate participants symptoms using the CGI-I as well as severity of depression by the Montgomery-Åsberg Depression (MADRS), quality of life (Q-LES-Q), social and occupational functioning (SOFAS), and functional impairment (LIFE–RIFT). Participants were asked to assess their symptom improvement with the PGI-I. Bland-Altman agreement plots and Intra-class correlations were used to evaluate agreement, and Spearman correlation coefficients were implemented to examine convergent validity. Sub-group analyses for disorder type (bipolar and major depression) were performed. There was high agreement between the PGI-I and CGI-I ratings across follow-up time points (weeks 2, 4, 6, 8, 12, 16, 20, 24, and 28). Similar results were observed in male only and female only data and after adjustment for age and gender. Both PGI-I and CGI-I ratings were robustly positively correlated with MADRS, and LIFE-RIFT and negatively correlated with SOFAS and Q-LES-Q, supporting the convergent validity of the PGI-I. Sub-group analyses for bipolar and major depressive disorder showed similar findings. Our findings support the utility of the PGI-I as a participant rated measure of global improvement among in iduals with bipolar or major depressive disorders.
Publisher: Cambridge University Press (CUP)
Date: 10-2009
DOI: 10.1111/J.1601-5215.2009.00415.X
Abstract: To evaluate the effect of N -acetylcysteine (NAC) on substance use in a double-blind, placebo-controlled trial of NAC in bipolar disorder. It is hypothesised that NAC will be superior to placebo for reducing scores on the Clinical Global Impressions scale for Substance Use (CGI-SU). Participants were randomised to 6-months of treatment with 2 g/day NAC ( n = 38) or placebo ( n = 37). Substance use was assessed at baseline using the Habits instrument. Change in substance use was assessed at regular study visits using the CGI-SU. Amongst the 75 participants 78.7% drank alcohol (any frequency), 45.3% smoked tobacco and 92% consumer caffeine. Other substances were used by fewer than six participants. Caffeine use was significantly lower for NAC-treated participants compared with placebo at week 2 of treatment but not at other study visits. NAC appeared to have little effect on substance use in this population. A larger study on a substance using population will be necessary to determine if NAC may be a useful treatment for substance use.
Publisher: Frontiers Media SA
Date: 09-04-2014
Publisher: Royal College of Psychiatrists
Date: 07-2017
DOI: 10.1192/BJP.BP.116.193789
Abstract: Recent data might subtly recalibrate the risk/benefit ratio of lithium, the prototypical mood stabiliser for bipolar disorder. There are hints that lithium might be associated with a reduction in dementia risk and as noted in this Journal , a surprising reduction in the risk of cancer.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2015
Publisher: SAGE Publications
Date: 23-09-2021
Abstract: Certain nutrient supplements (nutraceuticals) may target neurobiological pathways perturbed in bipolar disorder (BD) such as inflammation, oxidative stress, and mitochondrial dysfunction. Nutraceuticals thus may have a potential role as adjunctive treatments for BD. A search of Embase via embase.com, PubMed via PubMed, Cumulated index to nursing and allied health literature (CINAHL) Complete via EBSCO, and Cochrane Central Register of Controlled Clinical Trials via cochranelibrary.com was conducted to identify published randomized controlled trials assessing the efficacy of nutraceuticals on mood symptomatology in adults with BD. Search terms for BD, nutraceuticals, and clinical trials (total search terms = 75) were used to search from inception to February 20, 2020. The Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials was used to assess the risk of bias. A total of 1,712 studies were identified through the search. After rigorous screening, 22 studies were included in the review. There was large variability across the studies with 15 different nutraceutical agents assessed and as such insufficient homogeneity for a meta-analysis to be conducted ( I 2 50%). Studies revealed promising, albeit conflicting, evidence for omega-3 fatty acids and N-acetylcysteine. Isolated positive results were reported for coenzyme Q10. Given nutraceuticals are tolerable and accessible, they may be useful as potential adjunctive treatments for BD. Nutraceuticals targeting neuroinflammation or mitochondrial activity may have the most potential for the depressive phase. However, further studies are required to determine efficacy.
Publisher: SAGE Publications
Date: 28-03-2018
Publisher: Elsevier BV
Date: 12-2017
Publisher: Public Library of Science (PLoS)
Date: 16-05-2013
Publisher: SPIE-Intl Soc Optical Eng
Date: 25-06-2015
Location: Australia
Start Date: 2019
End Date: 2022
Funder: Marsden Fund
View Funded ActivityStart Date: 03-2018
End Date: 10-2023
Amount: $2,962,655.00
Funder: Australian Research Council
View Funded Activity