ORCID Profile
0000-0002-4792-6068
Current Organisations
Queensland Centre for Mental Health Research
,
Aarhus University
,
University of Queensland
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Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.PSYNEUEN.2006.12.006
Abstract: Developmental vitamin D (DVD) deficiency alters brain development and behaviour in the rat. The aim of this study was to vary levels of vitamin D deficiency during gestation and examine the effects on developmental milestones and behaviour in adult offspring. By manipulating the withdrawal and reintroduction of vitamin D in the diet of female Sprague-Dawley rats, their offspring were subjected to four different prenatal vitamin D conditions: (a) control (normal vitamin D throughout gestation) (b) early-DVD deficiency (c) late-DVD deficiency and (d) full-DVD deficiency. We show that the standard measure for vitamin D status, 25(OH)D(3), can be significantly manipulated within 7 days by dietary intervention. We also show that levels of the active form of this vitamin, 1,25(OH)(2)D(3), replete within the same time frame as 25(OH)D(3) but are slower to deplete. Developmental milestones remained normal across all four dietary groups. Concerning the adult behavioural phenotype, both full- and late-DVD deficiency were associated with MK-801-induced hyperlocomotion. Overall, these data suggest that vitamin D deficiency restricted to late gestation only is sufficient to disrupt adult brain functioning in the rat. These findings suggest there may be a therapeutic window for maternal dietary intervention in the DVD model of psychosis.
Publisher: Cambridge University Press (CUP)
Date: 2013
DOI: 10.1016/J.EURPSY.2011.09.004
Abstract: Delusional-like experiences (DLE) have been associated with low income, suggesting that more broadly defined socio-economic disadvantage may be associated with these experiences. We had the opportunity to explore the association between DLE and both in idual- and area-level measures of socio-economic disadvantage. Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. The Composite International Diagnostic Interview was used to identify DLE, common psychiatric disorders, and physical disorders. In idual-level and area-level socio-economic disadvantage measures were available based on variables including income, educational attainment, employment status, and housing. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors. Of the 8773 subjects, 8.4% ( n = 776) positively endorsed one or more DLE. DLE screen items were more likely to be endorsed by those who were (a) younger, (b) never married, or widowed, separated or orced status, (c) migrants, or (d) living in rented houses. There were significant associations between socio-economic disadvantage and increased DLE endorsement, and this was found for both in idual-level and area-level measures of socio-economic disadvantage. In general, the associations remained significant after adjusting for a range of potential confounding factors and in planned sensitivity analyses. DLE are associated with socio-economic disadvantage in the general population. We speculate that the link between socio-economic disadvantage and DLE may be mediated by psychosocial stress and general psychological distress.
Publisher: Cold Spring Harbor Laboratory
Date: 15-11-2022
DOI: 10.1101/2022.11.09.22281216
Abstract: The complement system, including complement components 3 and 4 (C3, C4), traditionally has been linked to innate immunity. More recently, complement components have also been implicated in brain development and the risk of schizophrenia. Based on a large, population-based case-cohort study, we measured the blood concentrations of C3 and C4 in 68,768 neonates. We found a strong correlation between the concentrations of C3 and C4 (phenotypic correlation = 0.65, P -value 1.0×10 −100 , genetic correlation = 0.38, P -value = 1.9×10 −35 ). A genome-wide association study (GWAS) for C4 protein concentration identified 36 independent loci, 30 of which were in or near the major histocompatibility complex on chromosome 6 (which includes the C4 gene), while six loci were found on six other chromosomes. A GWAS for C3 identified 15 independent loci, seven of which were located in the C3 gene on chromosome 19, and eight loci on five other chromosomes. We found no association between (a) measured neonatal C3 and C4 concentrations, imputed C4 haplotypes, or predicted C4 gene expression, with (b) schizophrenia (SCZ), bipolar disorder (BIP), depression (DEP), autism spectrum disorder, attention deficit hyperactivity disorder or anorexia nervosa diagnosed in later life. Mendelian randomisation (MR) suggested a small positive association between higher C4 protein concentration and an increased risk of SCZ, BIP, and DEP, but these findings did not persist in more stringent analyses. Evidence from MR supported causal relationships between C4 concentration and several autoimmune disorders: systemic lupus erythematosus (SLE, OR and 95% confidence interval, 0.37, 0.34 – 0.42) type-1 diabetes (T1D, 0.54, 0.50 - 0.58) multiple sclerosis (MS, 0.68, 0.63 - 0.74) rheumatoid arthritis (0.85, 0.80 - 0.91) and Crohn’s disease (1.26, 1.19 - 1.34). A phenome-wide association study (PheWAS) in UK Biobank confirmed that the genetic correlates of C4 concentration were associated a range of autoimmune disorders including coeliac disease, thyrotoxicosis, hypothyroidism, T1D, sarcoidosis, psoriasis, SLE and ankylosing spondylitis. We found no evidence of associations between C3 versus mental or autoimmune disorders based on either MR or PheWAS. In general, our results do not support the hypothesis that C4 is causally associated with the risk of SCZ (nor several other mental disorders). We provide new evidence to support the hypothesis that higher C4 concentration is associated with lower risks of autoimmune disorders.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Cold Spring Harbor Laboratory
Date: 21-04-2021
DOI: 10.1101/2021.04.20.440585
Abstract: Genome-wide association studies (GWAS) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age-of-onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Here we present LT-FH++, an extension of the liability threshold model conditioned on family history (LT-FH), that jointly accounts for age-of-onset and sex, as well as family history. Using simulations, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields large power gains over both LT-FH and genome-wide association study by proxy (GWAX). We applied our method to four psychiatric disorders available in the iPSYCH data, and to mortality in the UK Biobank, finding 20 genome-wide significant associations with LT-FH++, compared to 10 for LT-FH and 8 for a standard case-control GWAS. As more genetic data with linked electronic health records become available to researchers, we expect methods that account for additional health information, such as LT-FH++, to become even more beneficial.
Publisher: Oxford University Press (OUP)
Date: 08-2013
Publisher: Oxford University Press (OUP)
Date: 05-08-2020
Publisher: SAGE Publications
Date: 08-1996
DOI: 10.3109/00048679609065020
Abstract: Objective: To review the clinical features, neurobiological correlates and treatment of pathological laughing and crying. Method: Selective literature review. Results: Attacks of involuntary, irresistible laughing or crying have long been recognised as sequelae of brain damage. There is controversy about the clinical features of these attacks, the stimuli that provoke them and their relation to affective disorder. The pathophysiology of pathological laughing and crying is still unclear. It can occur in the presence of focal as well as diffuse brain disease. Treatment with antidepressant medications has been found to be of benefit in patients with cerebrovascular disease and multiple sclerosis. Conclusions: Clinicians should remain vigilant for these symptoms, and offer effective treatments, such as antidepressants, where indicated. Further research is needed to delineate the underlying neurobiological correlates of pathological laughing and crying. The efficacy of both pharmacological and non-pharmacological interventions requires critical evaluation.
Publisher: Wiley
Date: 05-2003
DOI: 10.1034/J.1600-0447.2003.00053.X
Abstract: The aim of this study was to systematically examine ancient Roman and Greek texts to identify descriptions of schizophrenia and related disorders. Material from Greek and Roman literature dating from the 5th Century BC to the beginning of the 2nd Century AD was systematically reviewed for symptoms of mental illness. DSM IV criteria were applied in order to identify material related to schizophrenia and related disorders. The general public had an awareness of psychotic disorders, because the symptoms were described in works of fiction and in historical accounts of malingering. There were isolated instances of text related to psychotic symptoms in the residents of ancient Rome and Greece, but no written material describing a condition that would meet modern diagnostic criteria for schizophrenia. In contrast to many other psychiatric disorders that are represented in ancient Greek and Roman literature, there were no descriptions of in iduals with schizophrenia in the material assessed in this review.
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: 08-2006
DOI: 10.1016/J.NEUROIMAGE.2006.03.003
Abstract: MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 in iduals with schizophrenia compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were nonlinearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal-thalamic circuitry in schizophrenia.
Publisher: Elsevier BV
Date: 1993
DOI: 10.1016/0006-3223(93)90282-I
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a lethal virus that causes COVID-19 (Coronavirus disease 2019), the respiratory illness that has caused the COVID-19 pandemic. Even though multiple pharmacological trials are ongoing, there is no proof that any treatment will effectively cure or prevent COVID-19. Currently, COVID-19-infected patients are being managed with non-specific medications to suppress the symptoms and other associated co-morbidities. Nitric oxide is a bio-signaling molecule that has been shown to be effective for treating several viral infections in humans. Household Natural foods rich in nitrites and nitrates (NO donors) have been scientifically proven to have therapeutic benefits against immune-related respiratory tract infections. It was understood that NO could inhibit the early stage of SARS CoV-2 invasion into the human cell. Fruits and vegetables containing nitrites and nitrates have been revised and are now thought to be potential anti-CoV agents for effective control of other associated systemic disorders. The purpose of this review is to highlight some key facts about the treatment and prevention of COVID-19 infection with foods rich in nitric oxide and its donors. PRACTICAL APPLICATIONS: Improving the body's immune system is the early step to be considered as a preventive measure to stop the spreading of COVID-19 infection. Emerging research continues to mount that dietary nitrates/nitrites from plant foods are being healthy as well as keep us away from infectious diseases. They are now incorporated into low-risk adjuvant therapy for various infections and systemic disorders. This concept portrays the regular consuming foods such as fruits and vegetables that are rich in nitric oxide which have the potential to promote health, improve general well-being, and reduce the risk associated with the highly contagious diseases. Hence, we recommend adding nitrates and nitrites-containing food to the regular diet to improve the self-immunity as well as to fight against COVID-19 disease.
Publisher: Elsevier BV
Date: 05-2004
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.PNPBP.2004.05.045
Abstract: The authors evaluated the efficacy of cholinergic drugs in the treatment of neuroleptic-induced tar e dyskinesia (TD) by a systematic review of the literature on the following agents: choline, lecithin, physostigmine, tacrine, 7-methoxyacridine, ipidacrine, galantamine, donepezil, rivastigmine, eptastigmine, metrifonate, arecoline, RS 86, xanomeline, cevimeline, deanol, and meclofenoxate. All relevant randomized controlled trials, without any language or year limitations, were obtained from the Cochrane Schizophrenia Group's Register of Trials. Trials were classified according to their methodological quality. For binary and continuous data, relative risks (RR) and weighted or standardized mean differences (SMD) were calculated, respectively. Eleven trials with a total of 261 randomized patients were included in the meta-analysis. Cholinergic drugs showed a minor trend for improvement of tar e dyskinesia symptoms, but results were not statistically significant (RR 0.84, 95% confidence interval (CI) 0.68 to 1.04, p=0.11). Despite an extensive search of the literature, eligible data for the meta-analysis were few and no results reached statistical significance. In conclusion, we found no evidence to support administration of the old cholinergic agents lecithin, deanol, and meclofenoxate to patients with tar e dyskinesia. In addition, two trials were found on novel cholinergic Alzheimer drugs in tar e dyskinesia, one of which was ongoing. Further investigation of the clinical effects of novel cholinergic agents in tar e dyskinesia is warranted.
Publisher: American Medical Association (AMA)
Date: 2007
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.SCHRES.2018.05.013
Abstract: Cross-sectional studies have suggested inhalant use is associated with psychosis. This association was examined in a longitudinal study accounting for other substance use and potential confounders. We used a prospective s le (N = 6542) from the Northern Finland Birth Cohort 1986. Self-report questionnaires on substance use and psychotic experiences were completed when the cohort members were 15-16 years old. Inhalant use was categorized into four groups (never, once, 2-4 times, 5 times or more). Subsequent psychosis diagnoses (ICD-10) until age 30 years were obtained from national registers. Cox regression analysis was used to examine the association between adolescent inhalant use and risk of psychosis. During the observation period 124 in iduals were diagnosed with incident psychosis. Overall, there were 225 (3.4%) subjects with any inhalant use, 18 (8.0%) of whom were diagnosed with psychosis during the follow up. Of non-inhalant users (n = 6317) 106 (1.7%) were diagnosed with psychosis. Compared to non-users, those using inhalants had increased risk of incident psychosis with most frequent inhalant use associated with the greatest risk (unadjusted HR = 9.46 3.86-23.20). After adjusting for baseline psychotic experiences, other substance use, comorbid mental disorder and parental substance abuse, the increased risk of psychosis persisted (HR = 3.06 1.05-8.95). Furthermore, a dose-response effect between inhalant use and risk of psychosis was identified (OR = 2.34 1.83-2.99). Inhalant use in adolescence was independently associated with incident psychosis. The adverse health outcomes associated with adolescent inhalant use provide compelling reasons for implementation of policies to reduce the use of volatile substances in adolescents.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.SCHRES.2005.10.012
Abstract: We previously demonstrated that olfactory cultures from in iduals with schizophrenia had increased cell proliferation compared to cultures from healthy controls. The aims of this study were to (a) replicate this observation in a new group of in iduals with schizophrenia, (b) examine the specificity of these findings by including in iduals with bipolar I disorder and (c) explore gene expression differences that may underlie cell cycle differences in these diseases. Compared to controls (n = 10), there was significantly more mitosis in schizophrenia patient cultures (n = 8) and significantly more cell death in the bipolar I disorder patient cultures (n = 8). Microarray data showed alterations to the cell cycle and phosphatidylinositol signalling pathways in schizophrenia and bipolar I disorder, respectively. Whilst caution is required in the interpretation of the array results, the study provides evidence indicating that cell proliferation and cell death in olfactory neuroepithelial cultures is differentially altered in schizophrenia and bipolar disorder.
Publisher: Cambridge University Press (CUP)
Date: 23-11-2005
DOI: 10.1017/S0033291705006392
Abstract: Background. Apart from in iduals with clinical psychosis, community surveys have shown that many otherwise well in iduals endorse items designed to identify psychosis. The aim of this study was to characterize the demographic correlates of in iduals who endorse psychosis screening items in a large general community s le. Method. The National Survey of Mental Health and Wellbeing interviewed 10641 in iduals living in private dwellings in Australia. As part of a diagnostic interview (the CIDI), respondents were asked between three and six items originally designed to screen for potential psychosis. We examined the impact of selected demographic variables on endorsement of these items including sex, age, marital status, migrant status, urban/rural status, employment, education, and socio-economic status. Results. An estimated 11·7% of the Australian population endorsed at least one psychosis-screening item. Significantly higher endorsement was associated with younger age, migrants from non-English-speaking backgrounds, those who had never married or who were orced/separated or unemployed, those living in urban regions and those from the lowest socio-economic levels. Conclusions. Many of the correlates of endorsement of psychosis-screen items are also associated with psychosis. Unravelling the factors that contribute to this broader non-clinical phenotype will aid our understanding of psychosis.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.BIOPSYCH.2013.01.020
Abstract: Evidence from genetic association studies implicate genes involved in neural migration associated with schizophrenia risk. Neural stem rogenitor cell cultures (neurosphere-derived cells) from olfactory mucosa of schizophrenia patients have significantly dysregulated expression of genes in focal adhesion kinase (FAK) signaling, a key pathway regulating cell adhesion and migration. The aim of this study was to investigate whether olfactory neurosphere-derived cells from schizophrenia patients have altered cell adhesion, cell motility, and focal adhesion dynamics. Olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects were used. Cells were assayed for cell adhesion and cell motility and analyzed for integrins and FAK proteins. Focal adhesions were counted and measured in fixed cells, and time-lapse imaging was used to assess cell motility and focal adhesion dynamics. Patient-derived cells were less adhesive and more motile than cells derived from healthy control subjects, and their motility was reduced to control cell levels by integrin-blocking antibodies and by inhibition of FAK. Vinculin-stained focal adhesion complexes were significantly smaller and fewer in patient cells. Time-lapse imaging of cells expressing FAK tagged with green fluorescent protein revealed that the disassembly of focal adhesions was significantly faster in patient cells. The evidence for altered motility and focal adhesion dynamics in patient-derived cells is consistent with dysregulated gene expression in the FAK signaling pathway in these cells. Alterations in cell adhesion dynamics and cell motility could bias the trajectory of brain development in schizophrenia.
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJOPEN-2019-032580
Abstract: Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of in iduals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. A total of 20 689 participants were recruited through the Australian Department of Human Services and a media c aign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA s le (75%) were sent a saliva kit in the mail. 95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the s le report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the s le report responding well to the first antidepressant they were prescribed. A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2019
Publisher: Wiley
Date: 2005
DOI: 10.1111/J.1600-0447.2004.00467.X
Abstract: Science needs to constantly match research models against the data. With respect to the epidemiology of schizophrenia, the widely held belief that the incidence of schizophrenia shows little variation may no longer be supported by the data. The aims of this paper are (i) to explore data-vs.-belief mismatch with respect to the incidence of schizophrenia, and (ii) to speculate on the causes and consequences of such discrepancies. Based on a recently published systematic review of the incidence of schizophrenia, the distribution of incidence rates around the world was examined. In order to examine if the incidence of schizophrenia differed by sex, male vs. female risk ratios were generated. The distribution of incidence rates for schizophrenia is asymmetrical with many high rates skewing the distribution. Based on the central 80% of rates, the incidence of schizophrenia varies in a five-fold range (between 7.7 and 43.0 per 100,000). Males have a significantly higher incidence of schizophrenia compared with females (median male to female risk ratio = 1.4), and this difference could not be accounted for by diagnostic criteria or age range. The beliefs that (i) the incidence of schizophrenia does not vary between sites and (ii) males and females are equally affected, may have persisted because of an unspoken deeper belief that schizophrenia is an egalitarian and exceptional disorder. Our ability to generate productive hypotheses about the aetiology of schizophrenia rests on an accurate appraisal of the data. Beliefs not supported by data should be identified and relabelled as myths.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2019
DOI: 10.1007/S00127-019-01756-0
Abstract: In iduals with schizophrenia have been reported to have low employment rates. We examined the associations of schizophrenia with employment, income, and status of cohabitation from a work life course perspective. Nationwide cohort study including all in iduals (n = 2,390,127) born in Denmark between 1955 and 1991, who were alive at their 25th birthday. Diagnosis of schizophrenia (yes/no) between ages 15 and 25 was used as an exposure. Employment status, annual wage or self-employment earnings, level of education, and cohabitant status from the age of 25-61 (years 1980-2016) were used as outcomes. Schizophrenia diagnosis between ages 15 and 25 (n = 9448) was associated with higher odds of not being employed (at the age of 30: OR 39.4, 95% CI 36.5-42.6), having no secondary or higher education (7.4, 7.0-7.8), and living alone (7.6, 7.2-8.1). These odds ratios were two-to-three times lower and decreasing over time for those in iduals who did not receive treatment in a psychiatric inpatient or outpatient clinic for schizophrenia after the age of 25. Between ages 25-61, in iduals with schizophrenia have cumulative earning of $224,000, which is 14% of the amount that the in iduals who have not been diagnosed with schizophrenia earn. In iduals with schizophrenia are at high risk of being outside the labour market and living alone throughout their entire life, resulting in an enormous societal loss in earnings. In iduals with less chronic course of schizophrenia had a gradual but substantial improvement throughout their work life.
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: Elsevier BV
Date: 05-2015
Publisher: SAGE Publications
Date: 2008
DOI: 10.1080/00048670802050595
Abstract: Objective: Several large population-based studies have reported that otherwise-well in iduals endorse items related to delusion-like experiences. The aim of the present study was to examine selected correlates of delusion-like experiences in a s le of non-psychotic in iduals. Method: Subjects (n=310) were screened with the Diagnostic Interview for Psychosis in order to exclude psychotic disorders. Delusion-like experiences were assessed with the Peters Delusional Inventory (PDI). Non-parametric statistics were used to assess the relationship between total PDI score and a range of demographic (age, sex, migrant status, paternal age), physical (minor physical anomalies) symptom-related variables (hallucinations, awareness of thought disorder) and family history of mental illness. Results: The median (range) PDI score was 4 (0–26), while one-third of the subjects endorsed seven or more items. The presence of a family history of any psychiatric condition was significantly correlated with a higher PDI score. PDI score was significantly positively correlated with endorsement of hallucinations and awareness of thought disorder. PDI was not significantly associated with sex, family history of schizophrenia, paternal age, migrant status nor scores related to minor physical anomalies. There was a trend level association between younger age and higher PDI score. Conclusion: Delusion-like experiences are relatively common in non-psychotic in iduals. The association with a family history of mental disorders provides clues to the mechanisms underlying the profile of delusion-like experience.
Publisher: Wiley
Date: 14-07-2017
DOI: 10.1016/J.IJDEVNEU.2017.07.002
Abstract: Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat brain.
Publisher: Wiley
Date: 03-2001
DOI: 10.1034/J.1600-0447.2001.00114.X
Abstract: The aims of this study were to examine working memory in the acute subacute phase of schizophrenia and mania and to examine correlations between working memory and specific symptom domains. Visuospatial working memory and symptom profiles were assessed in three groups (schizophrenia group, n= 19 mania, n= 12 controls, n= 19) on two occasions separated by 4 weeks. Both patient groups had significant deficits on working memory compared to the well controls and the schizophrenia and mania groups were equally impaired. All groups showed equivalent improvement over time. In the patient groups, impaired working memory was significantly correlated with the presence of both negative symptoms and positive thought disorder. Impaired working memory is found in both schizophrenia and mania during the acute subacute phases. Further research is required in order to clarify the neurocognitive mechanisms linking impaired working memory with both negative symptoms and positive thought disorder.
Publisher: Springer Science and Business Media LLC
Date: 12-2020
DOI: 10.1186/S13229-020-00399-2
Abstract: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which are more common in males. The ‘prenatal sex steroid’ hypothesis links excessive sex-steroid exposure during foetal life with the behavioural differences observed in ASD. However, the reason why sex steroid exposure may be excessive remains unclear. Epidemiological studies have identified several environmental risk factors associated with ASD, including developmental vitamin D (DVD) deficiency. We have demonstrated in an animal model that DVD-deficiency is associated with a hyper-inflammatory response in placentas from male but not female foetuses. Vitamin D also regulates the expression of several steroidogenic enzymes in vitro. Therefore using this animal model, we have examined whether DVD-deficiency leads to increased sex-steroid levels in both the maternal and foetal compartments. Female rats are fed a vitamin D deficient diet from 6 weeks before mating until tissue collection at embryonic day 18. We examined the levels of testosterone, androstenedione and corticosterone in maternal plasma, foetal brains and amniotic fluid. We further examined gene expressions of steroidogenic enzymes and DNA methylation of aromatase promoters in foetal brains as a potential molecular mechanism regulating testosterone expression. We show that DVD-deficiency increases testosterone levels in maternal blood. We also show elevated levels of testosterone and androstenedione in the amniotic fluid of female but not male DVD-deficient foetuses. Testosterone levels were also elevated in DVD-deficient male brains. Vitamin D, like other steroid-related hormones, regulates gene expression via methylation. Therefore we examined whether the significant elevation in testosterone in male brains was due to such a potential gene-silencing mechanism. We show that the promoter of aromatase was hyper-methylated compared to male controls. A reduction in aromatase, in addition to causing excessive testosterone, could also lead to a reduction in estradiol which was not examined here. This study is the first to show how an epidemiologically established environmental risk factor for ASD may selectively elevate testosterone in male embryonic brains. These findings provide further mechanistic support for the prenatal sex steroid theory of ASD.
Publisher: Public Library of Science (PLoS)
Date: 29-09-2017
Publisher: American Medical Association (AMA)
Date: 05-2016
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.BIOPSYCH.2006.02.033
Abstract: Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2018
Publisher: American Psychiatric Association Publishing
Date: 10-2016
Publisher: Elsevier BV
Date: 03-2001
Publisher: Cambridge University Press (CUP)
Date: 2020
DOI: 10.1017/S2045796020000517
Abstract: Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across in iduals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment. IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys ( n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment. The lifetime prevalence of IED in all countries was 0.8% ( s.e. : 0.0). The two subtypes involving anger attacks that harmed people (‘hurt people only’ and ‘destroy property and hurt people’), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with ( v . those without) comorbid disorders, and among those who perpetrated more violent assaults. The most common IED behavioural subtypes in these general population s les are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.
Publisher: SAGE Publications
Date: 29-09-2016
Publisher: Public Library of Science (PLoS)
Date: 11-06-2008
Publisher: Cambridge University Press (CUP)
Date: 2020
DOI: 10.1017/S2045796020000633
Abstract: Epidemiological studies indicate that in iduals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a erse range of population-based surveys. The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women. Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4 range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs. Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
Publisher: Springer Science and Business Media LLC
Date: 08-2008
DOI: 10.1038/454824B
Publisher: Elsevier BV
Date: 02-1999
DOI: 10.1016/S0920-9964(98)00139-X
Abstract: Data from the Northern Hemisphere support an excess of winter-spring births of in iduals who later develop schizophrenia when compared with the general population. The data from the Southern Hemisphere have been less consistent. This paper will present a systematic review and meta-analysis of relevant data from the Southern Hemisphere. To identify relevant studies we searched electronic databases, reviewed citations from target publications and wrote letters to published authors in the field. The counts for observed and expected births were assessed in four planned comparisons. In the absence of significant heterogeneity, the data were combined using Mantel-Haenzel odds ratio in a fixed effect model. Twelve studies were identified. Published and unpublished data from eight of these were able to be included in the analyses. For the two seasonal comparisons (n = 20,017), small but non-significant excesses were found in the first comparison (winter versus other seasons OR = 1.04, 0.99-1.08) and for the second comparison (winter and spring versus other seasons OR = 1.03, 0.99-1.07). For the two quarterly comparisons (n = 14,799), there was a small but non-significant excess found in the third comparison (third quarter versus other quarters OR = 1.03, 0.98-1.09), and a small but non-significant deficit in the fourth comparison (third and fourth quarter versus other quarters OR = 0.99, 0.95-1.04). Assuming that season of birth acts as a proxy marker for fluctuating non-genetic risk-modifying factors for schizophrenia, this review suggests that in the Southern Hemisphere these factors may be weaker, less prevalent, less regular, and/or may be modified by other confounding or modifying variables.
Publisher: SAGE Publications
Date: 20-08-2016
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.DRUGALCDEP.2021.109158
Abstract: We examined prevalence and factors associated with receiving perceived helpful alcohol use disorder (AUD) treatment, and persistence in help-seeking after earlier unhelpful treatment. Data came from 27 community epidemiologic surveys of adults in 24 countries using the World Health Organization World Mental Health surveys (n = 93,843). Participants with a lifetime history of treated AUD were asked if they ever received helpful AUD treatment, and how many professionals they had talked to up to and including the first time they received helpful treatment (or how many ever, if they had not received helpful treatment). 11.8% of respondents with lifetime AUD reported ever obtaining treatment (n = 9378) of these, 44% reported that treatment was helpful. The probability of obtaining helpful treatment from the first professional seen was 21.8% the conditional probability of subsequent professionals being helpful after earlier unhelpful treatment tended to decrease as more professionals were seen. The cumulative probability of receiving helpful treatment at least once increased from 21.8% after the first professional to 79.7% after the seventh professional seen, following earlier unhelpful treatment. However, the cumulative probability of persisting with up to seven professionals in the face of prior treatments being unhelpful was only 13.2%. Fewer than half of people with AUDs who sought treatment found treatment helpful the most important factor was persistence in seeking further treatment if a previous professional had not helped. Future research should examine how to increase the likelihood that AUD treatment is found to be helpful on any given contact.
Publisher: Cambridge University Press (CUP)
Date: 12-2020
DOI: 10.1017/THG.2020.83
Abstract: The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years ( N = 876 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair s les to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this s le indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Publisher: Elsevier BV
Date: 12-2009
Publisher: American Medical Association (AMA)
Date: 05-2002
DOI: 10.1001/ARCHPSYC.59.5.458
Abstract: The aim of this study was to examine minor physical anomalies and quantitative measures of the head and face in patients with psychosis vs healthy controls. Based on a comprehensive prevalence study of psychosis, we recruited 310 in iduals with psychosis and 303 controls. From this s le, we matched 180 case-control pairs for age and sex. In idual minor physical anomalies and quantitative measures related to head size and facial height and depth were compared within the matched pairs. Based on all subjects, we examined the specificity of the findings by comparing craniofacial summary scores in patients with nonaffective or affective psychosis and controls. The odds of having a psychotic disorder were increased in those with wider skull bases (odds ratio [OR], 1.40 95% confidence interval [CI], 1.02-1.17), smaller lower-facial heights (glabella to subnasal) (OR, 0.57 95% CI, 0.44-0.75), protruding ears (OR, 1.72 95% CI, 1.05-2.82), and shorter (OR, 2.29 95% CI, 1.37-3.82) and wider (OR, 2.28 95% CI, 1.43-3.65) palates. Compared with controls, those with psychotic disorder had skulls that were more brachycephalic. These differences were found to distinguish patients with nonaffective and affective psychoses from controls. Several of the features that differentiate patients from controls relate to the development of the neuro-basicranial complex and the adjacent temporal and frontal lobes. Future research should examine both the temporal lobe and the middle cranial fossa to reconcile our anthropomorphic findings and the literature showing smaller temporal lobes in patients with schizophrenia. Closer attention to the skull base may provide clues to the nature and timing of altered brain development in patients with psychosis.
Publisher: Elsevier BV
Date: 08-2003
Publisher: Elsevier BV
Date: 04-2004
Publisher: Public Library of Science (PLoS)
Date: 09-08-2013
Publisher: Springer Science and Business Media LLC
Date: 19-11-2016
Publisher: BMJ
Date: 03-2018
DOI: 10.1136/BMJOPEN-2017-018959
Abstract: The Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin S le (BLTS). Twins and their non-twin siblings from Queensland, Australia mostly from European ancestry. Data were collected between 2009 and 2016 on 2773 participants (age range 18–38, 57.8% female, 372 complete monozygotic pairs, 493 dizygotic pairs, 640 non-twin siblings, 403 singleton twins). A structured clinical assessment (Composite International Diagnostic Interview) was used to collect lifetime prevalence of diagnostic statistical manual (4th edition) (DSM-IV) diagnoses of major depressive disorder, (hypo)mania, social anxiety, cannabis use disorder, alcohol use disorder, panic disorder and psychotic symptoms. Here, we further describe the comorbidities and ages of onset for these mental disorders. Notably, two-thirds of the s le reported one or more lifetime mental disorder. In addition, the 19Up study assessed general health, drug use, work activity, education level, personality, migraine/headaches, suicidal thoughts, attention deficit hyperactivity disorder (ADHD) symptomatology, sleep–wake patterns, romantic preferences, friendships, familial environment, stress, anorexia and bulimia as well as baldness, acne, asthma, endometriosis, joint flexibility and internet use. The overlap with previous waves of the BLTS means that 84% of the 19Up participants are genotyped, 36% imaged using multimodal MRI and most have been assessed for psychological symptoms at up to four time points. Furthermore, IQ is available for 57%, parental report of ADHD symptomatology for 100% and electroencephalography for 30%. The 19Up study complements a phenotypically rich, longitudinal collection of environmental and psychological risk factors. Future publications will explore hypotheses related to disease onset and development across the waves of the cohort. A follow-up study at 25+years is ongoing.
Publisher: Springer Science and Business Media LLC
Date: 06-2004
DOI: 10.1007/S00127-004-0819-4
Abstract: While much attention has been given to the prediction of violent offending behaviour amongst people with psychotic disorders, less attention has been given to the fact that these same in iduals are often the victims of violence. In this paper, we examine victimisation amongst participants in a prevalence study of psychosis, and describe demographic and clinical correlates of victimisation. METHOD The study was based on the Australian National Survey of Mental Health and Wellbeing--Low Prevalence (Psychotic) Disorders. The participants were asked if they had been a victim of violence in the previous year. The association between selected demographic and clinical variables and being a victim of violence was examined using logistic regression. Of the 962 in iduals with psychosis, 172 reported being a victim of violence in the past 12 months (17.9 %). The odds of being a victim were increased in those who: (a) were female, (b) were homeless, (c) had a lifetime history of substance abuse, (d) had been arrested in the previous 12 months, (e) had poorer social and occupational function, and (f) had higher scores on the disorganisation summary score. Clinicians should remain mindful that one out of every six in iduals with a psychotic disorder reports being a victim of violence in the previous year. Models of care that address issues related to symptom relief, accommodation, and exposure to high-crime areas may reduce the rates of victimisation amongst those with psychotic disorders.
Publisher: Public Library of Science (PLoS)
Date: 31-05-2005
Publisher: SAGE Publications
Date: 28-10-2021
DOI: 10.1177/00048674211054740
Abstract: Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in diagnostic criteria and in the overall study design. The aim of this study was to systematically review and, where appropriate, meta-analyse estimates related to the pairwise comorbidity between mood disorders and substance-related disorders, after sorting these estimates by various study designs. We searched PubMed (MEDLINE), Embase, CINAHL and Web of Science for publications between 1980 and 2017 regardless of geographical location and language. We meta-analysed estimates from original articles in 4 broadly defined mood and 35 substance-related disorders. After multiple eligibility steps, we included 120 studies for quantitative analysis. In general, regardless of variations in diagnosis type, temporal order or use of adjustments, there was substantial comorbidity between mood and substance-related disorders. We found a sixfold elevated risk between broadly defined mood disorder and drug dependence (odds ratio = 5.7) and fivefold risk between depression and cannabis dependence (odds ratio = 4.9) while the highest pooled estimate, based on period prevalence risk, was found between broadly defined dysthymic disorder and drug dependence (odds ratio = 11.3). Based on 56 separate meta-analyses, all pooled odds ratios were above 1, and 46 were significantly greater than 1 (i.e. the 95% confidence intervals did not include 1). This review found robust and consistent evidence of an increased risk of comorbidity between many combinations of mood and substance-related disorders. We also identified a number of under-researched mood and substance-related disorders, suitable for future scrutiny. This review reinforces the need for clinicians to remain vigilant in order to promptly identify and treat these common types of comorbidity.
Publisher: Springer Science and Business Media LLC
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 13-12-2018
DOI: 10.1038/S41467-018-07708-7
Abstract: Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study ( n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. In iduals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale. Effects of specific locales vary substantially within the most densely populated city of Denmark, with hazard ratios ranging from 0.26 to 9.26 for environment and from 0.20 to 5.95 for gene-by-environment. These findings indicate the critical synergism of gene and environment on the etiology of schizophrenia and demonstrate the potential of incorporating geolocation in genetic studies.
Publisher: Public Library of Science (PLoS)
Date: 24-10-2013
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.SCHRES.2006.03.016
Abstract: The aim of this study was to investigate whether there is an increased susceptibility to apoptosis in cultured fibroblasts from patients with schizophrenia. Dermal fibroblasts were collected and cultured from three groups: patients with schizophrenia, patients with non-schizophrenic psychosis, and healthy comparison subjects. Susceptibility to apoptosis was measured at the level of degradation product (proportion of cells in the sub-G0 cell cycle fraction in which apoptotic bodies accumulate), pro-apoptotic effector (activated caspase-3), and molecular regulators (P53, Bax and Bcl-2). Cell lines were studied under both basal culture and cycloheximide (an apoptotic inducer) exposure conditions. Consistent with increased susceptibility to apoptosis, the proportion of sub-G0 cells under basal conditions was significantly larger in the schizophrenia group, compared to the non-schizophrenic psychosis group. However when apoptosis was stimulated with cycloheximide, the schizophrenia group showed an attenuated caspase-3 response. The pattern of correlations between regulators, caspase-3 and the proportion of sub-G0 cells was different in the schizophrenia group, consistent with group-specific apoptotic pathway dysregulation. The study demonstrated anomalous apoptotic mechanisms in schizophrenia, which appear not to affect non-schizophrenia psychosis patients. The detection of these anomalies in fibroblasts suggests that altered apoptosis may be observable in all somatic cell types in schizophrenia.
Publisher: Elsevier
Date: 2017
Publisher: Elsevier BV
Date: 10-2017
Publisher: Korean College of Neuropsychopharmacology
Date: 31-05-2019
Publisher: American Medical Association (AMA)
Date: 10-2017
Publisher: Springer Science and Business Media LLC
Date: 10-11-2017
DOI: 10.1038/S41598-017-11852-3
Abstract: Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-in idual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1016/S0920-9964(99)00021-3
Abstract: This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tar e dyskinesia (TD) and, where appropriate, to combine the data for meta-analysis. Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Meta-analysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the in idual trials identified tended to have small s le sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and erse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2018
Publisher: Elsevier BV
Date: 10-2020
Publisher: Emerald
Date: 11-07-2016
DOI: 10.1108/JACPR-11-2015-0196
Abstract: – Whilst overt bullying has received considerable attention for its negative impact on the emotional well-being of children and adolescents, peer problems such as excessive teasing and social exclusion have received less consideration. The purpose of this paper is to examine the prevalence, demographic, and clinical correlates of frequent peer problems in children and adolescents who participated in the Australian National Survey of Mental Health and Well-Being. – Participants were a nationally representative s le of 2,107 children (aged 6-12 years), and 1,490 adolescents (aged 13-17 years). Frequent peer problems (excessive teasing or social exclusion) were measured by parental report for children, and self and parental report for adolescents. Associations with a number of mental health problems were examined, including being in the clinical range for internalising and externalising symptoms, having major depressive disorder, attention deficit hyperactivity disorder or conduct disorder, low self-esteem, experiencing suicidal ideation and behaviour, or using marijuana and alcohol. – One in 30 children and one in 20 adolescents experienced frequent peer problems. Parents less commonly identified frequent peer problems than were self-reported by their adolescent children. Frequent peer problems were strongly associated with all mental health problems except alcohol and marijuana use. – Frequent peer problems are associated with a greatly increased risk of mental health problems. Identifying those children and adolescents with frequent peer problems provides opportunity for assessment and intervention of emotional and behavioural problems.
Publisher: AMPCo
Date: 02-2013
DOI: 10.5694/MJA11.11592
Abstract: • The recommended level for serum 25-hydroxyvitamin D (25(OH)D) in infants, children, adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10-20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring. • Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation, assuming minimal sun exposure. • Risk factors for low vitamin D are: lack of skin exposure to sunlight, dark skin, southerly latitude, conditions affecting vitamin D metabolism and storage (including obesity) and, for infants, being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor. • Targeted measurement of 25(OH)D levels is recommended for infants, children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit. • Vitamin D deficiency can be treated with daily low-dose vitamin D supplements, although barriers to adherence have been identified. High-dose intermittent vitamin D can be used in children and adolescents. Treatment should be paired with health education and advice about sensible sun exposure. Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D₃ daily for at least the first year of life. • There is increasing evidence of an association between low vitamin D and a range of non-bone health outcomes, however there is a lack of data from robust randomised controlled trials of vitamin D supplementation.
Publisher: American Medical Association (AMA)
Date: 10-2007
DOI: 10.1001/ARCHPSYC.64.10.1123
Abstract: Despite improvements in mental health services in recent decades, it is unclear whether the risk of mortality in schizophrenia has changed over time. To explore the distribution of standardized mortality ratios (SMRs) for people with schizophrenia. Broad search terms were used in MEDLINE, PsychINFO, Web of Science, and Google Scholar to identify all studies that investigated mortality in schizophrenia, published between January 1, 1980, and January 31, 2006. References were also identified from review articles, reference lists, and communication with authors. Population-based studies that reported primary data on deaths in people with schizophrenia. Operationalized criteria were used to extract key study features and mortality data. We examined the distribution of SMRs and pooled selected estimates using random-effects meta-analysis. We identified 37 articles drawn from 25 different nations. The median SMR for all persons for all-cause mortality was 2.58 (10%-90% quantile, 1.18-5.76), with a corresponding random-effects pooled SMR of 2.50 (95% confidence interval, 2.18-2.43). No sex difference was detected. Suicide was associated with the highest SMR (12.86) however, most of the major causes-of-death categories were found to be elevated in people with schizophrenia. The SMRs for all-cause mortality have increased during recent decades (P = .03). With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention.
Publisher: Cambridge University Press (CUP)
Date: 2020
DOI: 10.1017/S204579602000075X
Abstract: To identify and synthesise the literature on the cost of mental disorders. Systematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980–May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses (2) diagnosis of at least one mental disorder (3) study population based on the general population (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783). In total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: con . This is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.
Publisher: American Medical Association (AMA)
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 31-07-2017
Publisher: American Medical Association (AMA)
Date: 03-2017
Publisher: Springer Science and Business Media LLC
Date: 28-05-2013
DOI: 10.1038/MP.2013.69
Publisher: SAGE Publications
Date: 04-1997
DOI: 10.3109/00048679709073828
Abstract: Objective: As part of a randomised double-blind study of a new atypical antipsychotic we sought to determine both the levels of visual acuity and the occurrence of toxic side-effects in a group of patients treated for many years on a variety of antipsychotics. Method: Twenty-three inpatients with a DSM-III-R diagnosis of chronic schizophrenia from two separate hospital locations who met the criteria for the double-blind trial were examined for ocular abnormalities at both baseline and at trial completion. Results: At baseline a high prevalence of abnormalities was identified: 19 patients (82.6%) were found to have one or more ocular abnormalities, including lens opacities/cataracts and corneal pigmentation three patients, with delusions related to the sun, were noted to have solar burns a high proportion (almost 70%) of patients had untreated visual acuity problems. No further changes were observed at the follow-up examinations. Conclusions: The possible causes of ocular disturbance in schizophrenia and the reasons for the relatively high ocular morbidity in this group are thought to result from both illness-related factors and the effects of antipsychotic medication. Causality is confounded by a number of issues such as the high prevalence of smoking, poor general health and the variety of antipsychotic medications used in the treatment of psychosis as well as substance abuse. The clinical implications are considered in this paper in relation to the move towards community-based psychiatric services.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.EARLHUMDEV.2015.03.010
Abstract: Many environmental factors have been shown to influence birth weight (BW) and one of these are season of birth. The aim of the present study was to investigate the seasonal variation in BW in Denmark during 1936-1989, and to see if the variation could be explained by sunshine exposure during pregnancy. The study population was selected from the Copenhagen School Health Records Register and included 276 339 children born between 1936 and 1989. Seasonal variation was modeled using a non-stationary sinusoidal model that allowed the underlying trend in BW and the litude and phase of the yearly cycles to change. There was a clear seasonal pattern in BW which, however, changed gradually across the study period. The highest BWs were seen during fall (September - October) from 1936 to 1963, but a new peak gradually grew from the early 1940s during early summer (May - June) and became the highest from 1964 to 1989. The litude of the fall peak started at 25.5 (95%CI 24.6 25.9) grams and gradually disappeared. The litude of the early summer peak gradually arose from nothing to a peak of 18.6 (95%CI 17.7 19.6) grams in the mid 1980s where it started to decrease again. Sunshine did not explain the seasonal variation in BW. There was a clear seasonal pattern in BW in Denmark 1936-1989, which however changed across the study period. Throughout the study period we observed a peak in BW during the fall, but gradually, starting in the early 1940s, an additional early summer peak emerged and became the highest from 1964 and onwards.
Publisher: SAGE Publications
Date: 05-12-2016
Abstract: The objective is to summarise recent findings from the 2010 Australian Survey of High Impact Psychosis (SHIP) and examine their implications for future policy and planning to improve mental health, physical health and other circumstances of people with a psychotic disorder. Survey of High Impact Psychosis collected nationally representative data on 1825 people with psychotic illness. Over 60 papers have been published covering key challenges reported by participants: financial problems, loneliness and social isolation, unemployment, poor physical health, uncontrolled symptoms of mental illness, and lack of stable, suitable housing. Findings are summarised under the rubric of participant-ranked top challenges. The main income source for the majority (85%) of participants was a government benefit. Only one-third was employed, and the most appropriate employment services for this group were under-utilised. High rates of loneliness and social isolation impacted mental and physical health. The rate of cardiometabolic disease was well above the general population rate, and associated risk factors were present from a very young age. Childhood abuse (30.6%), adult violent victimisation (16.4%) and alcohol and substance abuse/dependence (lifetime rates of 50.5% and 54.5%, respectively) complicated the clinical profile. Treatment with medication was suboptimal, with physical health conditions undertreated, a high rate of psychotropic polypharmacy and underutilisation of clozapine in chronic persistent psychotic illness. Only 38.6% received evidence-based psychosocial therapies. In the previous year, 27.4% had changed housing and 12.8% had been homeless, on average for 155 days. Money, social engagement and employment are the most important challenges for people with psychotic illness, as well as good physical and mental health. An integrated approach to recovery is needed to optimise service delivery and augment evidence-based clinical practice with measures to improve physical health and social circumstances. Meeting these challenges has the potential to reduce costs to government and society, as well as promote recovery.
Publisher: Elsevier BV
Date: 12-1999
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.NBD.2012.10.023
Abstract: Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2022
DOI: 10.1186/S13104-022-06077-1
Abstract: We developed an assay to measure the concentration of 25 hydroxyvitamin D 2 and D 3 in protein extracts derived from stored neonatal dried blood spots. During this study, we postulated that these s les had been contaminated with exogenous vitamin D metabolites because of the addition of bovine serum albumin (BSA) as part of an extraction step undertaken 7 years earlier. The aim of the current study was to develop methods in order to adjust for this contamination. We identified between-plate variations in 25 hydroxyvitamin D 2 and D 3 concentrations which suggested the presence of three different BSA batches. Based on repeat extraction (without the addition of BSA) and testing of 395 s les, we developed models to correct for the exogenous 25 hydroxyvitamin D 2 and D 3. The regression models were Diff 25OHD3 = − 8.2 + 1.8* Diff 25OHD2 for low contamination, Diff 25OHD3 = 23.8 + 1.7* Diff 25OHD2 for middle contamination, and Diff 25OHD3 = 14.3 + 3.0* Diff 25OHD2 for high contamination. After these corrections, the three subs les had comparable distributions within the expected range for both 25 hydroxyvitamin D 2 and D 3 .
Publisher: Springer Science and Business Media LLC
Date: 10-07-2019
DOI: 10.1038/S41467-019-11039-6
Abstract: There are established associations between advanced paternal age and offspring risk for psychiatric and developmental disorders. These are commonly attributed to genetic mutations, especially de novo single nucleotide variants (dnSNVs), that accumulate with increasing paternal age. However, the actual magnitude of risk from such mutations in the male germline is unknown. Quantifying this risk would clarify the clinical significance of delayed paternity. Using parent-child trio whole-exome-sequencing data, we estimate the relationship between paternal-age-related dnSNVs and risk for five disorders: autism spectrum disorder (ASD), congenital heart disease, neurodevelopmental disorders with epilepsy, intellectual disability and schizophrenia (SCZ). Using Danish registry data, we investigate whether epidemiologic associations between each disorder and older fatherhood are consistent with the estimated role of dnSNVs. We find that paternal-age-related dnSNVs confer a small amount of risk for these disorders. For ASD and SCZ, epidemiologic associations with delayed paternity reflect factors that may not increase with age.
Publisher: American Medical Association (AMA)
Date: 07-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: Springer Science and Business Media LLC
Date: 06-1996
DOI: 10.1007/BF02247331
Publisher: Elsevier BV
Date: 02-2005
Publisher: Elsevier BV
Date: 06-2003
DOI: 10.1016/S0920-9964(02)00226-8
Abstract: Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study s le consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small s le size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.
Publisher: Elsevier BV
Date: 2000
Publisher: Cambridge University Press (CUP)
Date: 27-11-2017
DOI: 10.1017/S0033291717003336
Abstract: The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data. Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI). Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes). The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.
Publisher: Springer Science and Business Media LLC
Date: 11-2001
Abstract: Urban birth and migrant status have been identified as risk factors for psychosis in North American and European studies. The aim of this study was to explore these variables in an Australian case-control study. Country of birth of subjects and their parents, and place of birth of Australian-born subjects, were examined in in iduals with psychosis drawn from a prevalence study (n = 310) and well controls recruited from the same catchment area (n = 303). Migrant status was associated with a significantly decreased odds of having a psychotic disorder. For those born in Australia, neither migrant status of parents nor urban birth was associated with having a psychotic disorder. The lack of effect for urban birth and second-generation migrant status may help generate candidate environmental risk factors that operate in Europe but not in Australia.
Publisher: Royal College of Psychiatrists
Date: 12-2017
DOI: 10.1192/BJP.BP.117.205955
Abstract: Traumatic events are associated with increased risk of psychotic experiences, but it is unclear whether this association is explained by mental disorders prior to psychotic experience onset. To investigate the associations between traumatic events and subsequent psychotic experience onset after adjusting for post-traumatic stress disorder and other mental disorders. We assessed 29 traumatic event types and psychotic experiences from the World Mental Health surveys and examined the associations of traumatic events with subsequent psychotic experience onset with and without adjustments for mental disorders. Respondents with any traumatic events had three times the odds of other respondents of subsequently developing psychotic experiences (OR=3.1, 95% CI 2.7–3.7), with variability in strength of association across traumatic event types. These associations persisted after adjustment for mental disorders. Exposure to traumatic events predicts subsequent onset of psychotic experiences even after adjusting for comorbid mental disorders.
Publisher: Cold Spring Harbor Laboratory
Date: 06-12-2019
DOI: 10.1101/860767
Abstract: Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identified 143 independent loci in 112 1-Mb regions providing new insights into the physiology of vitamin D and implicating genes involved in (a) lipid and lipoprotein metabolism, (b) dermal tissue properties, and (c) the sulphonation and glucuronidation of 25OHD. Mendelian randomization models found no robust evidence that 25OHD concentration had causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes had (direct or indirect) causal effects on 25OHD concentration, clarifying the relationship between 25OHD status and health.
Publisher: American Medical Association (AMA)
Date: 05-2019
Publisher: Cambridge University Press (CUP)
Date: 02-05-2017
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.SCHRES.2013.05.015
Abstract: Low early life vitamin D status is associated with an increased risk of schizophrenia and psychotic experiences. Here we examine if maternal pregnancy vitamin D concentrations are associated with offspring psychotic experiences as young adults. A community s le of 2047 participants was investigated. Maternal prenatal 25 hydroxyvitamin D (25(OH)D) concentrations were assessed with tandem mass spectroscopy. Psychotic experiences were assessed at age 18years using a semi-structured clinical interview. 177 cohort members reported suspected or definite psychotic experiences, There was no evidence of an association between maternal 25(OH)D concentrations as quartiles (p=0.85 hypothesis test of general association versus no association across the quartiles) or as a continuous variable (p=0.89) versus experience of suspected and definite psychotic experiences at 18years. Within the cohort, only 29 subjects met criteria for a psychotic disorder at age 18. Based on this s le, there was no significant association between maternal 25(OH)D and psychotic disorder at 18years. Maternal vitamin D levels were not associated with risk of psychotic experiences nor psychotic disorders in this birth cohort.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.PSYNEUEN.2006.05.006
Abstract: Developmental vitamin D deficiency (DVD) has been shown to alter the orderly pattern of brain development. Even though the period of vitamin D deficiency is restricted to gestation this is sufficient to induce behavioural abnormalities in the adult offspring consistent with those seen in many animal models of schizophrenia. Given that some of these behavioural alterations could also be an indirect result of either impaired maternal hypothalamic pituitary axis (HPA) function (which in turn could influence maternal care) or the result of a permanent alteration in HPA function in the adult offspring we have examined HPA status in both maternal animals and adult offspring. In this study we have established that HPA function is normal in the maternally vitamin D deficient rat. We replicate the behavioural phenotype of hyperlocomotion whilst establishing that HPA function is also unchanged in the adult male offspring. We conclude that the behavioural alterations induced by DVD deficiency are due to some adverse event in brain development rather than via an alteration in stress response.
Publisher: Elsevier BV
Date: 05-2012
Publisher: Springer Science and Business Media LLC
Date: 19-09-2017
DOI: 10.1038/MP.2017.196
Publisher: Public Library of Science (PLoS)
Date: 06-03-2020
Publisher: Cambridge University Press (CUP)
Date: 06-2008
DOI: 10.1017/S0140525X08004251
Abstract: Crespi & Badcock (C& B) present an appealing and parsimonious synthesis arguing that schizophrenia and autism are differentially regulated by maternal versus paternal genomic imprinting, respectively. We argue that animal models related to schizophrenia and autism provide a useful platform to explore the mechanisms outlined by C& B. We also note that schizophrenia and autism share certain risk factors such as advanced paternal age. Apart from genomic imprinting, copy number variants related to advanced paternal age may also contribute to the differential trajectory of brain development associated with autism and schizophrenia.
Publisher: Elsevier BV
Date: 09-2017
Publisher: American Medical Association (AMA)
Date: 08-12-2020
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.PSYCHRES.2011.12.027
Abstract: We contrasted demographic and clinical characteristics in transethnic schizophrenia populations from Australia (n=821), India (n=520) and Sarawak, Malaysia (n=298) and proposed cultural explanations for identified site differences. From these we aimed to identify candidate variables free from significant cultural confounding that are hence suitable for inclusion in genetic analyses. We observed five phenomena: (1) more in iduals were living alone in Australia than India or Sarawak (2) drug use was lower in India than Australia or Sarawak (3) duration of untreated psychosis (DUP) was longer in India than Australia or Sarawak (4) the rate of schizoaffective disorder was lower in India than Australia or Sarawak and (5) age at psychosis onset (AAO) was older in Sarawak than Australia or India. We suggest that site differences for living arrangements, drug use and DUP are culturally confounded. The schizoaffective site difference likely results from measurement bias. The AAO site difference, however, has no obvious cultural or measurement bias explanation. Therefore, this may be an ideal candidate for use in genetic studies, given that genetic variants affecting AAO have already been proposed.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.SCHRES.2013.02.025
Abstract: The objective of this study is to describe secular trends in the average age of death in patients with schizophrenia and to compare these with the general population. This is a longitudinal linkage study from 1 January 1980 to 31 December 2010 using the Danish Psychiatric Research Register and the Danish Cause of Death Register. Data were analyzed using descriptive statistics and survival analysis. The average age of death in the schizophrenia population (62.2 years 95% CI, 61.9-62.5) was lower compared to the general population (73.4 years 95% CI, 73.4-73.4), P<0.001. In the general population we found, for men, an average increase in the age of death of 0.28 years (95% CI, 0.27-0.28) per calendar year, and for women an increase in age of death of 0.31 years (95% CI, 0.31-0.32) per calendar year (both P<0.001). In contrast, age of death decreased in the schizophrenia population: the change in average age of death for males was 0.04 years (95% CI, -0.09 to 0.00) per calendar year (P<0.05), and the comparable estimate for females was -0.05 years (95% CI, -0.09 to 0.01) per calendar year (P<0.05). A similar pattern existed after acts of self-harm as cause of death were excluded from the analyses. Patients diagnosed with schizophrenia had an increased mortality rate compared with the general population (hazard ratio, 2.05 95% CI, 2.01-2.09). On average, patients with schizophrenia die younger than the general population, independent of intentional self-harm as cause of death.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 11-1995
Publisher: SAGE Publications
Date: 26-02-2015
Abstract: To describe the prevalence and demographic, clinical and functional correlates of childhood trauma in patients attending early psychosis clinics. Participants were recruited from outpatients attending four early psychosis services. Exposure to childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Psychopathology was measured using the Positive and Negative Syndrome Scale and the Depression, Anxiety and Stress Scale. Social and vocational functioning and substance use were also assessed. Over three-quarters of the 100 patients reported exposure to any childhood trauma. Emotional, physical and sexual abuse were reported by 54%, 23% and 28% of patients, respectively, while 49% and 42% of patients reported emotional and physical neglect, respectively. Female participants were significantly more likely to be exposed to emotional and sexual abuse. Exposure to childhood trauma was correlated with positive psychotic symptoms and higher levels of depressive, anxiety and stress symptoms however, it had no impact on social or vocational functioning or recent substance use. Exposure to childhood trauma was common in patients with early psychosis, and associated with increased symptomatology. Existing recommendations that standard clinical assessment of patients with early psychosis should include inquiry into exposure to childhood trauma are supported.
Publisher: Cold Spring Harbor Laboratory
Date: 04-0004
DOI: 10.1101/146670
Abstract: The iPSYCH consortium has established a large Danish population-based Case-Cohort s le (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 s le is nested within the entire Danish population born 1981-2005 including 1,472,762 persons. This paper introduces the iPSYCH2012 s le and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3,540), autism (N=16,146), ADHD (N=18,726), and affective disorder (N=26,380), of which 1928 had bipolar affective disorder. Controls were randomly s led in iduals (N=30,000). Within the s le of 86,189 in iduals, a total of 57,377 in iduals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot s les obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the s le. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each in idual, the iPSYCH2012 s le also includes longitudinal information on health, prescribed medicine, social and socioeconomic information and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 s le is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.BRAINRESBULL.2004.12.007
Abstract: There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2016
DOI: 10.1038/NG.3577
Abstract: The offspring of older fathers have higher risk of psychiatric disorders such as schizophrenia and autism. Paternal-age-related de novo mutations are widely assumed to be the underlying causal mechanism, and, although such mutations must logically make some contribution, there are alternative explanations (for ex le, elevated liability to psychiatric illness may delay fatherhood). We used population genetic models based on empirical observations of key parameters (for ex le, mutation rate, prevalence, and heritability) to assess the genetic relationship between paternal age and risk of psychiatric illness. These models suggest that age-related mutations are unlikely to explain much of the increased risk of psychiatric disorders in children of older fathers. Conversely, a model incorporating a weak correlation between age at first child and liability to psychiatric illness matched epidemiological observations. Our results suggest that genetic risk factors shared by older fathers and their offspring are a credible alternative explanation to de novo mutations for risk to children of older fathers.
Publisher: SAGE Publications
Date: 13-01-2075
Abstract: Antipsychotic drug treatment alters status on key risk factors for cardiovascular disease. The aim of this study was to test whether cardiovascular risk factor associations differ in adults with psychosis and adults from the general community. Data were analysed for those aged 25–64 years from a nationally representative psychosis s le ( n = 1,457) and a national comparator s le ( n = 8,866). The Pearson correlation coefficient was used to estimate the association among tobacco use, body mass index, waist circumference, diastolic and systolic blood pressure and fasting total-, LDL- and HDL-cholesterol, triglycerides and plasma glucose. The robust Levene test was used to test for s le differences in variance. Correlations among cardiovascular risk indicators and between cardiovascular risk indicators and age were often significantly weaker in those with psychosis than in those from the national comparator s le. This was not due to a reduction in variance within the psychosis s le. Risk prediction that synthesizes multivariate risk indicator data needs to be connected to verified cardiovascular morbidity and mortality in those with psychosis to determine if standard risk calculators adequately discriminate those at high, medium and low future risk of cardiovascular morbidity and mortality. Until then the clinical implications of low or absent correlations among cardiovascular risk indicators and their low or absent association with increasing age is unclear but may indicate that risk equations commonly used in the general population may not be applicable for those with treated psychosis.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.SCHRES.2006.03.046
Abstract: There is a relative lack of information about the epidemiology of psychotic disorders in the developing world. The aim of this pragmatic study was to describe the correlates of first-episode psychosis in the central African nation of Zambia. Selected clinical and demographic variables were collected on patients with psychotic disorders presenting for the first time at the only psychiatric hospital in Zambia (Chainama Hills College Hospital, Lusaka). During the study period, 160 subjects were admitted to the hospital with the first episode of a psychotic disorder. The male to female sex ratio was 2.5:1, with the median age of first admission for both sexes being 26 years. Half of the subjects had a duration of untreated psychosis one month or less. Recent alcohol and other drug abuse was common in males (56%). Clinical evidence of HIV/AIDs was found in 9% of those admitted. Approximately one-third of the subjects had attended a traditional healer for their psychotic symptoms prior to admission. Understanding the profile of treated first-episode psychosis in the developing world can help optimize the development of local services. Furthermore, characterizing differences in the epidemiology of psychosis between populations may help generate factors that could influence its cause and course.
Publisher: Public Library of Science (PLoS)
Date: 11-06-2008
Publisher: Royal College of Psychiatrists
Date: 03-1991
Abstract: A common denominator can be found permeating thought disorder at various levels – the lack of executive planning and editing. With data available from aphasiology and neuropsychology, certain features of thought disorder can be reinterpreted as being consistent with dysfunction of the frontal lobe. It is hypothesised that thought disorder may reflect a dysfunction of the cortical–subcortical loops that project into the pre-frontal cortex. The hypothesis predicts that thought-disordered patients will have impaired performance on tests of frontal lobe function, regardless of diagnosis.
Publisher: SAGE Publications
Date: 10-2006
Publisher: Elsevier BV
Date: 28-02-2005
DOI: 10.1016/J.BBR.2004.07.008
Abstract: Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate homeostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 31-01-2018
DOI: 10.1038/S41398-017-0071-9
Abstract: The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For ex le, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function in the associative striatum, rather than the limbic striatum as previously presumed. Furthermore, subjects deemed at high risk of developing schizophrenia show similar presynaptic dopamine abnormalities in the associative striatum. Thus, our view of subcortical dopamine function in schizophrenia continues to evolve as we accommodate this newly acquired information. However, basic research in animal models has been slow to incorporate these clinical findings. For ex le, psychostimulant-induced locomotion, the commonly utilised phenotype for positive symptoms in rodents, is heavily associated with dopaminergic activation in the limbic striatum. This anatomical misalignment has brought into question how we assess positive symptoms in animal models and represents an opportunity for improved translation between basic and clinical research. The current review focuses on the role of subcortical dopamine dysfunction in psychosis and schizophrenia. We present and discuss alternative phenotypes that may provide a more translational approach to assess the neurobiology of positive symptoms in schizophrenia. Incorporation of recent clinical findings is essential if we are to develop meaningful translational animal models.
Publisher: Wiley
Date: 07-2003
DOI: 10.1002/NRC.10081
Publisher: Elsevier BV
Date: 02-2000
DOI: 10.1016/S0920-9964(99)00091-2
Abstract: Northern Hemisphere studies of first admissions for schizophrenia have shown an excess of summer admissions (June, July and August) compared to other times of the year. The within-year fluctuations in first admissions could be related to meteorological factors that fluctuate between seasons (e.g. temperature, photoperiod) and/or social factors (e.g. holidays, religious events). If meteorological factors were primarily responsible for the fluctuation, then Southern Hemisphere studies should find excess first admissions in December, January and February. This paper presents the first season of first admission study of schizophrenia in the Southern Hemisphere. The month and year of first admission for schizophrenia (ICD 8/9) for 4487 male and 3252 female, Australian-born in iduals were extracted from a Queensland mental health register. Spectral analysis showed a strong annual periodicity of first admissions for males with the peak in August (Southern Hemisphere winter) and a trough in the summer months (December to February). The pattern for females also displayed annual periodicity. These results correspond to the Northern Hemisphere reports of excess of schizophrenia first admissions in terms of the month of the year but not the season of excess. Further work is needed in order to clarify the impact of latitude and meteorological factors on the month of first admission for schizophrenia.
Publisher: AMPCo
Date: 10-2016
DOI: 10.5694/MJA16.00179
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.BBR.2005.02.015
Abstract: Based on clues from epidemiology, low prenatal vitamin D has been proposed as a candidate risk factor for schizophrenia. Recent animal experiments have demonstrated that transient prenatal vitamin D deficiency is associated with persistent alterations in brain morphology and neurotrophin expression. In order to explore the utility of the vitamin D animal model of schizophrenia, we examined different types of learning and memory in adult rats exposed to transient prenatal vitamin D deficiency. Compared to control animals, the prenatally deplete animals had a significant impairment of latent inhibition, a feature often associated with schizophrenia. In addition, the deplete group was (a) significantly impaired on hole board habituation and (b) significantly better at maintaining previously learnt rules of brightness discrimination in a Y-chamber. In contrast, the prenatally deplete animals showed no impairment on the spatial learning task in the radial maze, nor on two-way active avoidance learning in the shuttle-box. The results indicate that transient prenatal vitamin D depletion in the rat is associated with subtle and discrete alterations in learning and memory. The behavioural phenotype associated with this animal model may provide insights into the neurobiological correlates of the cognitive impairments of schizophrenia.
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: Springer Science and Business Media LLC
Date: 28-04-2004
Publisher: Cambridge University Press (CUP)
Date: 10-03-2016
Publisher: Elsevier BV
Date: 02-2004
DOI: 10.1016/S0920-9964(03)00130-0
Abstract: While there has been substantial research examining the correlates of comorbid substance abuse in psychotic disorders, it has been difficult to tease apart the relative importance of in idual variables. Multivariate analyses are required, in which the relative contributions of risk factors to specific forms of substance misuse are examined, while taking into account the effects of other important correlates. This study used multivariate correlates of several forms of comorbid substance misuse in a large epidemiological s le of 852 Australians with DSM-III-R-diagnosed psychoses. Multiple substance use was common and equally prevalent in nonaffective and affective psychoses. The most consistent correlate across the substance use disorders was male sex. Younger age groups were more likely to report the use of illegal drugs, while alcohol misuse was not associated with age. Side effects secondary to medication were associated with the misuse of cannabis and multiple substances, but not alcohol. Lower educational attainment was associated with cannabis misuse but not other forms of substance abuse. The profile of substance misuse in psychosis shows clinical and demographic gradients that can inform treatment and preventive research.
Publisher: SAGE Publications
Date: 19-05-2015
Abstract: Compared to the substantial body of research examining links between cannabis use and psychosis, there has been relatively little attention to the role of tobacco as a potential risk factor for psychosis. This study explored the association between age at first tobacco use and psychosis-related outcomes in a birth cohort. This study is based on a large birth cohort (the Mater-University Study of Pregnancy). At approximately 21 years of age, cohort members ( N = 3752) were assessed for three psychosis-related outcomes (International Classification of Diseases non-affective psychosis, the presence of any hallucination and total count of delusional-like experiences) with the Composite International Diagnostic Interview and the Peters Delusional Inventory. Associations between age at first tobacco use and psychosis-related outcomes were examined using logistic regression in a model (a) adjusted for sex and age and (b) in a second model excluding all respondents who had a history of past problematic and current cannabis use. When adjusted for age and sex, those who commenced tobacco at 15 years of age or younger were significantly more likely to (a) have non-affective psychosis, (b) be in the highest quartile of total score of the Peters Delusional Inventory and (c) report hallucinations. After excluding all those with a history of a cannabis use disorder, or who were current (last month) cannabis users, a significant association between age at first tobacco use and the presence of hallucinations persisted. There is an association between age at first tobacco use and subsequent psychosis-related outcomes in young adults. While the findings cannot be used to deduce causality, it adds weight to the hypothesis that early tobacco use may contribute to the risk of developing psychosis-related outcomes.
Publisher: Elsevier BV
Date: 08-1997
DOI: 10.1016/S0920-9964(97)00070-4
Abstract: To compare the performance of schizophrenia, mania and well control groups on tests sensitive to impaired executive ability, and to assess the within-group stability of these measures across the acute and subacute phases of psychoses. Recently admitted patients with schizophrenia (n = 36), mania (n = 18) and a well control group (n = 20) were assessed on two occasions separated by 4 weeks. Tests included: the Controlled Oral Word Association Test, the Stroop Test, the Wisconsin Card Sort Test, and the Trail Making Test. The two patient groups were significantly impaired on the Stroop Test at both time points compared to the control group. Significant group differences were also found for the Trail Making Test at Time 1 and for the Wisconsin Card Sort Test at Time 2. When controlled for practice effect, significant improvements over time were found on the Stroop and Trail Making tests in schizophrenia group and on WCST Categories Achieved in the mania group. Compared to controls, the patient groups were impaired on measures related to executive ability. The pattern of improvement on test scores between the acute and subacute phases differed between patients with schizophrenia versus patients with mania.
Publisher: Elsevier BV
Date: 07-1996
DOI: 10.1016/0920-9964(95)00013-5
Abstract: The aim of this study was to conduct an epidemiological analysis of quantitative dermatoglyphic traits as a marker of prenatal disturbance during the second trimester of life in schizophrenic patients. TFRC (Total Finger Ridge Count) and TABRC (Total a-b Ridge Count) were studied in a s le of 38 schizophrenic patients and 69 healthy in iduals. A significant decrease of the a-b ridge count was found in patients compared to controls, with a significant linear trend across the population distribution (OR linear trend = 1.6 95% CI = 1.0-2.4), indicating that the effect was not confined to a subgroup of cases with values in the lowest range. This finding was replicated in a second, larger s le (OR linear trend = 1.3 95% CI = 1.0-1.8). The suggestion that a-b ridge count is associated with genetic risk for schizophrenia needs to be investigated further. TFRC did not distinguish between patients and controls. The a-b ridge count may be a continuous risk factor for later schizophrenia, pointing towards a disturbance occurring during the second trimester of prenatal life, a period of critical CNS growth.
Publisher: Springer Science and Business Media LLC
Date: 06-03-2006
DOI: 10.1007/S00127-006-0041-7
Abstract: A recent systematic review found that the prevalence of schizophrenia was lower in developing nations compared to developed nations. However, there is a lack of information about the association between economic status and the incidence of schizophrenia. The aim of this study was to examine the association between economic status and the underlying incidence of schizophrenia based on a recently published systematic review of the incidence of schizophrenia. The analyses were based on 167 discrete incidence rates from 52 studies. Nations were ided into three categories according to per capita gross national product. Based on these categories, we compared the incidence rates for schizophrenia when adjusted for within-study variation. The median (and 10-90% quantiles) incidence rates per 100,000 persons for Least Developed Countries (three studies), Emerging Economies (nine studies), and Developed Countries (42 studies) were 20.0 (0.4-35.0), 11.0 (5.0-26.0) and 16.0 (8.0-48.0) respectively. There was no significant difference in incidence rates between these groups. While there is a lack of information on the incidence of schizophrenia in the developing world, there is no evidence to suggest that the incidence of schizophrenia varies by economic status. In light of the evidence that the prevalence of schizophrenia is higher in developed countries, more research is warranted focused on the interaction between economic measures, and the incidence, prevalence and course of schizophrenia.
Publisher: Wiley
Date: 2008
DOI: 10.1002/MPR.240
Publisher: S. Karger AG
Date: 2007
DOI: 10.1159/000108918
Abstract: i Background: /i Animal studies and in vitro experiments indicate that vitamin D is involved in a erse range of neurobiological functions. We had the opportunity to examine the relationship between serum 25-hydroxyvitamin D sub /sub [25(OH)D] levels and performance on various cognitive tasks, based on a large, representative community s le. i Methods: /i Three age groups were available from the population-based NHANES III survey: adolescent group (n = 1,676, age range 12–17 years), adult group (n = 4,747, 20–60 years), elderly group (n = 4,809, 60–90 years). The associations between eight psychometric measures and serum 25(OH)D were assessed. i Results: /i In the adolescent and adult groups, none of the psychometric measures were associated with 25(OH)D levels. In the elderly group there was a significant difference between 25(OH)D quintiles performance on a learning and memory task however, those with the highest quintile of 25(OH)D were most impaired on the task, contrary to the hypotheses. i Conclusion: /i Lower 25(OH)D levels were not associated with impaired performance on various psychometric measures. While it remains to be seen if chronic exposure to low 25(OH)D levels alters brain function in the long term, this cross-sectional study suggests that 25(OH)D levels do not influence neurocognitive performance.
Publisher: American Medical Association (AMA)
Date: 04-2021
Publisher: Wiley
Date: 14-04-2023
DOI: 10.1111/ACPS.13555
Abstract: Register‐based studies of major depressive disorder (MDD) do not capture all prevalent cases, as untreated cases and diagnoses made by general practitioners are not recorded in the registers. We examined the prevalence and agreement of survey‐ and register‐based measures of depression, and explored sociodemographic and health‐related factors that may have influenced this agreement. All 32,407 participants in the 2017 Central Denmark Region How are you? survey were linked to hospital and prescription records. A checklist for depressive symptoms within the last 14 days (Major Depression Inventory MDI) from the survey was compared with register‐based assessment of hospital‐diagnosed MDD and/or prescriptions for antidepressants. We estimated agreement between survey‐based and register‐based measures for depression and used logistic regression models to explore selected associated factors. In total, 5.9% of How are you? survey participants screened positive for current depression on the MDI. Of these, 51.3% (95% confidence interval (CI): 49.0–53.6) filled a prescription for an antidepressant medication during the 10 years prior or 2 years following the administration of the survey, and 14.5% (95% CI: 12.9–16.2) were treated for MDD in a psychiatric hospital‐based setting. When using a higher threshold of the MDI indicating more severe current depression, 22.8% (95% CI: 19.6–26.1) of those who screened positive also received an MDD diagnosis and 63.4% (95% CI: 59.7–67.2) were prescribed antidepressants during this 12‐year period. Among those with current depression, female sex, older age, chronic diseases, hospital‐treated self‐harm, and being permanently outside the workforce were associated with having a register‐based MDD diagnosis or antidepressant prescription. Among those with a register‐based depression record, female sex, younger age, hospital‐treated self‐harm, stress, and severe loneliness were associated with current depression. We found that as few as 15% of in iduals with current depression in the general Danish population were captured by the psychiatric hospital register, while 51% of these in iduals were identifiable in the prescription register. These findings demonstrate that register‐based measures significantly underestimate the true prevalence of depression by identifying only the cases that are most severe.
Publisher: SAGE Publications
Date: 21-12-2016
Abstract: Having sufficient sera concentrations of 25-hydroxyvitamin D is important for a range of health outcomes including cardiometabolic diseases. Clinical studies in people with psychotic disorders suggest that a sizable proportion has suboptimal vitamin D status (i.e. vitamin D deficiency or insufficiency). In iduals with psychosis also have many of the risk factors associated with suboptimal vitamin D status such as smoking, obesity, and reduced physical activity. The aim of this study was to examine the prevalence and socio-demographic and clinical correlates of vitamin D status using a large, population-based s le of adults with psychotic disorders. Data were collected as part of the Survey of High Impact Psychosis, a population-based survey of Australians aged 18-64 years with a psychotic disorder. 25-Hydroxyvitamin D concentration was measured in 463 participants. 25-Hydroxyvitamin D concentration was dichotomised into optimal (above 50 nmol/L) and suboptimal (below 50 nmol/L). The influence of a range of socio-demographic and clinical variables on vitamin D status was examined using logistic regression. Nearly half (43.6%) of the participants had suboptimal vitamin D status. Those with (a) increased physical activity or (b) positive symptoms had significantly reduced odds of having suboptimal vitamin D status. However, there were no significant associations between suboptimal vitamin D status and other psychiatric symptom measures or cardiometabolic risk factors. Many people with psychotic disorders have suboptimal vitamin D status. As part of the routine assessment of physical health status, clinicians should remain mindful of vitamin D status in this vulnerable population and encourage the use of appropriate vitamin D supplements.
Publisher: Wiley
Date: 02-05-2014
Publisher: Oxford University Press (OUP)
Date: 15-09-2006
Publisher: Wiley
Date: 27-01-2022
DOI: 10.1002/EAT.23687
Abstract: Previous literature has established an increased risk of eating disorders among in iduals with other psychiatric disorders and vice versa. However, often studies have focused on eating disorders as a single diagnostic entity and/or investigated selected psychiatric comorbidities. We conducted a comprehensive study, exploring bidirectional associations between different types of eating disorders and broad groups of all other psychiatric disorders, to identify patterns of comorbidity. We included all people born in Denmark 1963–2010. We collected information on eating disorders and considered the risk of subsequent psychiatric disorders using Cox‐proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered prior psychiatric disorders and subsequent eating disorders. An increased risk was seen for almost all disorder pairs of diagnoses evaluated. Following an anorexia nervosa (AN) diagnosis, the median hazard ratio for the different subsequent psychiatric disorders was 3.80 (range 2.48–6.15) following an other eating disorder (OED) diagnosis, it was 3.16 (range 2.05–5.14). After different psychiatric disorder diagnoses, the median hazard ratio was 2.66 for later AN (range 1.21–5.31), and 2.51 for later OED (range 1.25–4.10). Absolute risk of eating disorders was also higher among those with other psychiatric disorders than those without. In this broad examination, we identified bidirectional increases in risk of comorbidity for those with both eating disorder diagnoses and psychiatric disorder diagnoses. Although our findings indicate different patterns of comorbidity between eating disorders, these variations were generally small.
Publisher: Massachusetts Medical Society
Date: 30-04-2020
Publisher: Wiley
Date: 07-05-2022
DOI: 10.1002/WPS.20971
Abstract: Patient‐reported helpfulness of treatment is an important indicator of quality in patient‐centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post‐traumatic stress disorder, bipolar disorder, or alcohol use disorder. Data came from 30 community epidemiological surveys – 17 in high‐income countries (HICs) and 13 in low‐ and middle‐income countries (LMICs) – carried out as part of the World Health Organization (WHO)’s World Mental Health (WMH) Surveys. Respondents were asked whether treatment of each disorder was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Across all surveys and diagnostic categories, 26.1% of patients (N=10,035) reported being helped by the very first professional they saw. Persisting to a second professional after a first unhelpful treatment brought the cumulative probability of receiving helpful treatment to 51.2%. If patients persisted with up through eight professionals, the cumulative probability rose to 90.6%. However, only an estimated 22.8% of patients would have persisted in seeing these many professionals after repeatedly receiving treatments they considered not helpful. Although the proportion of in iduals with disorders who sought treatment was higher and they were more persistent in HICs than LMICs, proportional helpfulness among treated cases was no different between HICs and LMICs. A wide range of predictors of perceived treatment helpfulness were found, some of them consistent across diagnostic categories and others unique to specific disorders. These results provide novel information about patient evaluations of treatment across diagnoses and countries varying in income level, and suggest that a critical issue in improving the quality of care for mental disorders should be fostering persistence in professional help‐seeking if earlier treatments are not helpful.
Publisher: SAGE Publications
Date: 13-06-2012
Abstract: The 2010 Survey of High Impact Psychosis (SHIP) is Australia’s second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data. The survey covered 1.5 million people aged 18–64 years, approximately 10% of Australians in this age group. A two-phase design was used. In phase 1, screening for psychosis took place in public mental health services and non-government organizations supporting people with mental illness. In phase 2, 1825 of those screen-positive for psychosis were randomly selected and interviewed. Data collected included symptomatology, substance use, functioning, service utilization, medication use, education, employment, housing, and physical health including fasting blood s les. The estimated 1-month treated prevalence of psychotic disorders in public treatment services was 3.1 people per 1000 population the 12-month treated prevalence was 4.5 people per 1000. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia/schizoaffective disorder. One-half (49.5%) reported attempting suicide in their lifetime and two-thirds (63.2%) were rated as impaired in their ability to socialize. Over half (54.8%) had metabolic syndrome. The proportion currently smoking was 66.1%. Educational achievement was low. Only 21.5% were currently employed. Key changes in the 12 years since the first survey included: a marked drop in psychiatric inpatient admissions a large increase in the proportion attending community mental health clinics increased use of rehabilitation services and non-government organizations supporting people with mental illness a major shift from typical to atypical antipsychotics and large increases in the proportions with lifetime alcohol or drug abuse/dependence. People with psychotic illness face multiple challenges. An integrated approach to service provision is needed to ensure that their living requirements and needs for social participation are met, in addition to their very considerable mental and physical health needs.
Publisher: John Wiley & Sons, Ltd
Date: 18-07-2007
Publisher: Cambridge University Press (CUP)
Date: 2021
DOI: 10.1017/S2045796021000573
Abstract: Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes. Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries ( n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressive distress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning. Among respondents with 12-month MDD, 94.9% ( s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% ( s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4–1.6) and suicidality (OR = 1.5–2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD. These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in in iduals with MDD.
Publisher: American Medical Association (AMA)
Date: 02-2020
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: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
Publisher: Wiley
Date: 26-05-2023
DOI: 10.1111/ACPS.13565
Abstract: Schizophrenia spectrum disorders (SSD) comprise a group of related mental disorders, which share clinical features and common genetic disposition, but it is unknown if there is a diagnostic transition between these disorders over time. We aimed to study the incidence at the first SSD diagnosis between 2000 and 2018, defined as schizophrenia, schizotypal or schizoaffective disorder, and the early diagnostic transition between these disorders. Using Danish nationwide healthcare registers, we identified all in iduals aged 15–64 years during the period from 2000 to 2018 in Denmark and calculated the yearly incidence rates for the specific SSDs. We studied the diagnostic pathways from the first ever diagnosis of an SSD across the subsequent two treatment courses with an SSD diagnosis to evaluate early diagnostic stability, and explore potential changes over time. Among 21,538 patients, yearly incidence rates per 10,000 in iduals were similar during the observation period for schizophrenia (2000: 1.8 2018: 1.6), lower for schizoaffective disorder (2000: 0.3 2018: 0.1) and increasing for schizotypal disorder (2000: 0.7 2018: 1.3). Among the subgroup of 13,417 in iduals with three separate treatment courses, early diagnostic stability was present among 89.9% which differed between the disorders (schizophrenia: 95.4% schizotypal disorder: 78.0% schizoaffective disorder: 80.5%). Among 1352 (10.1%) experiencing an early diagnostic transition, 398 (3.0%) were diagnosed with schizotypal disorder after a schizophrenia or schizoaffective disorder diagnosis. This study provides comprehensive incidence rates for SSDs. The majority of patients experienced early diagnostic stability, but sizable proportions of people with initial schizophrenia or schizoaffective disorder are subsequently diagnosed with schizotypal disorder.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Springer Science and Business Media LLC
Date: 16-04-2019
Publisher: Wiley
Date: 24-05-2016
DOI: 10.1111/ACPS.12594
Abstract: In the light of the high prevalence of physical comorbidities in people with psychotic illness, there is a need to explore modifiable risk factors that may contribute to this disease burden. The benefits of physical activity to both physical and mental health have been well established. We aimed to examine the prevalence and correlates of physical activity in a national s le of adults living with psychotic illness. Physical activity was assessed in 1801 people using the International Physical Activity Questionnaire. Participants were dichotomised into low and moderate-high physical activity groups and associations between physical activity and a range of sociodemographic, clinical and physical comorbidity variables were examined using logistic regression. More than half the participants were categorised in the moderate-high physical activity group with nearly half of the s le engaged in physical activity every day. There were significant associations between low physical activity and older age, unemployment, educational non-participation, antipsychotic medication use, social dysfunction, self-reported loneliness and obesity. However, there was no significant association between physical activity and sex, psychosis type, illness duration, physical comorbidity or negative symptoms. The findings from this study may inform future interventions designed to increase physical activity in people with psychotic illness.
Publisher: Oxford University Press (OUP)
Date: 16-05-2020
Abstract: Childhood exposure to green space has previously been associated with lower risk of developing schizophrenia later in life. It is unclear whether this association is mediated by genetic liability or whether the 2 risk factors work additively. Here, we investigate possible gene–environment associations with the hazard ratio (HR) of schizophrenia by combining (1) an estimate of childhood exposure to residential-level green space based on the normalized difference vegetation index (NDVI) from Landsat satellite images, with (2) genetic liability estimates based on polygenic risk scores for 19 746 genotyped in iduals from the Danish iPSYCH s le. We used information from the Danish registers of health, residential address, and socioeconomic status to adjust HR estimates for established confounders, ie, parents’ socioeconomic status, and family history of mental illness. The adjusted HRs show that growing up surrounded by the highest compared to the lowest decile of NDVI was associated with a 0.52-fold (95% confidence interval [CI]: 0.40 to 0.66) lower schizophrenia risk, and children with the highest polygenic risk score had a 1.24-fold (95% CI: 1.18 to 1.30) higher schizophrenia risk. We found that NDVI explained 1.45% (95% CI: 1.07 to 1.90) of the variance on the liability scale, while polygenic risk score for schizophrenia explained 1.01% (95% CI: 0.77 to 1.46). Together they explained 2.40% (95% CI: 1.99 to 3.07) with no indication of a gene–environment interaction (P = .29). Our results suggest that risk of schizophrenia is associated additively with green space exposure and genetic liability, and provide no support for an environment-gene interaction between NDVI and schizophrenia.
Publisher: Oxford University Press (OUP)
Date: 02-04-2016
Publisher: Wiley
Date: 2006
DOI: 10.1002/AJHB.20504
Abstract: The association between vitamin D levels and skeletal growth has long been recognized. However, exposure to low levels of vitamin D during early life is also known to alter brain development, and is a candidate risk factor for schizophrenia. This study examines the association between four polymorphisms in the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three anthropometric variables (height, head size, and head shape). Four single-nucleotide polymorphisms (SNPs rs10735810/FokI, rs1544410/BsmI, rs7975232/ApaI, and rs731236/TaqI) in the VDR gene were genotyped in 179 in iduals with schizophrenia and 189 healthy controls. No significant associations were detected between any of the four VDR SNPs and risk of schizophrenia. Patients were slightly but significantly shorter compared to controls. Of the four SNPs, only rs10735810/FokI was associated with any of the anthropometric measures: the M4 isoform of this SNP was significantly associated with larger head size (P = 0.002). In light of the evidence demonstrating a role for vitamin D during brain development, the association between polymorphisms in VDR and brain development warrants closer scrutiny.
Publisher: Elsevier BV
Date: 1997
Publisher: American Medical Association (AMA)
Date: 28-12-2021
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.SCHRES.2008.05.022
Abstract: Recent systematic reviews have compiled estimates related to the incidence, prevalence and mortality associated with schizophrenia. The aims of this study were (a) to model various frequency measures, (b) to examine the consistency of the published versus the modelled estimates, and (c) to explore the relative change in prevalence estimates after adjustments were made to incidence, remission, and mortality estimates. We identified studies that provided matched incidence and prevalence estimates. We applied the DisMod software program to model incidence from observed prevalence estimates and vice versa. The accuracy of the modelled data was compared to the published data using Mann-Whitney Signed Rank tests. Finally, we conducted several 'thought experiments' to explore the impact of changing the incidence, remission, and mortality rates on prevalence estimates. We identified 24 matched-pairs of incidence and prevalence estimates. The distributions of modelled versus published estimates were significantly different. In 20 pairs, DisMod calculated modelled prevalence estimates that were higher than published estimates, while modelled incidence estimates were lower than published estimates in 21 pairs. In the majority of pairs, the difference between published and modelled estimates was greater than 50%. With respect to the 'thought experiments', a 25% reduction in mortality was associated with a 5-7% increase in prevalence, while 25% reduction in incidence or remission rates resulted in 18-23% and 1.2-2.4% decrease in prevalence estimates, respectively. The consistency between published incidence and prevalence estimates of schizophrenia is poor. Models can help interrogate these inconsistencies and provide insights into the dynamics of schizophrenia epidemiology.
Publisher: American Medical Association (AMA)
Date: 07-2018
Publisher: Elsevier
Date: 2017
Publisher: Elsevier BV
Date: 09-2017
Publisher: Elsevier BV
Date: 06-2003
DOI: 10.1016/S0304-3940(03)00303-3
Abstract: There is an accumulation of evidence implicating a role for vitamin D(3) in the developing brain. The receptor for this seco-steroid is expressed in both neurons and glial cells, it induces nerve growth factor (NGF) and it is a potent inhibitor of mitosis and promoter of differentiation in numerous cells. We have therefore assessed the direct effect of vitamin D(3) on mitosis, neurite outgrowth, as well as NGF production as a possible mediator of those effects, in developing neurons. Using cultured embryonic hippoc al cells and explants we found the addition of vitamin D(3) significantly decreases the percentage of cultured hippoc al cells undergoing mitosis in conjunction with increases in both neurite outgrowth and NGF production. The role of vitamin D(3) during brain development warrants closer scrutiny.
Publisher: SAGE Publications
Date: 19-02-2021
Publisher: Cambridge University Press (CUP)
Date: 23-09-2021
DOI: 10.1017/S0033291721003160
Abstract: The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries. Face-to-face interviews with community s les totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents. 3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness. ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population s le from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.
Publisher: Cold Spring Harbor Laboratory
Date: 03-05-2019
DOI: 10.1101/626762
Abstract: Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of in iduals who have been diagnosed with depression, and to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. This paper describes the recruitment and characteristics of the s le. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form, and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA s le were sent a saliva kit in the mail. A total of 20,689 participants, 75% of whom were female, enrolled in the study. The average age of participants was 43 years ± 15 years. 15,807 participants (76% of the participant group) returned saliva kits. The overwhelming majority of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a depressive episode. Rates of comorbidity with other psychiatric disorders were high. Two-thirds of the s le reported having taken more than one type of antidepressant during treatment for their depression. This study was effective in recruiting a large community s le of people with a history of clinical depression, highlighting the willingness of Australians to engage with medical research. A combination of recruitment through health records and media as well as use of an online questionnaire made it feasible to recruit the large s le needed for investigating the genetics of common diseases. It will be a valuable resource for investigating risk factors for depression, treatment response to antidepressants and susceptibility to side effects.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 06-11-2019
DOI: 10.1038/S41380-019-0578-Y
Abstract: Animal studies indicate that early life vitamin D is crucial for proper neurodevelopment. Few studies have examined whether maternal and neonatal vitamin D concentrations influence risk of autism spectrum disorders (ASD). Participants were s led from the Stockholm Youth Cohort, a register-based cohort in Sweden. Concentrations of total 25-hydroxyvitamin D (25OHD) were assessed from maternal and neonatal bios les using a highly sensitive liquid chromatography tandem mass spectrometry method. The maternal s le consisted of 449 ASD cases and 574 controls, the neonatal s le: 1399 ASD cases and 1607 controls and the paired maternal-neonatal s le: 340 ASD cases and 426 controls. Maternal 25OHD was not associated with child ASD in the overall s le. However, in Nordic-born mothers, maternal 25OHD insufficiency (25 − nmol/L) at ~11 weeks gestation was associated with 1.58 times higher odds of ASD (95% CI: 1.00, 2.49) as compared with 25OHD sufficiency (≥50 nmol/L). Neonatal 25OHD 25 nmol/L was associated with 1.33 times higher odds of ASD (95% CI: 1.02, 1.75) as compared with 25OHD ≥ 50 nmol/L. Sibling-matched control analyses indicated these associations were not likely due to familial confounding. Children with both maternal 25OHD and neonatal 25OHD below the median had 1.75 (95% CI: 1.08, 2.86) times the odds of ASD compared with children with maternal and neonatal 25OHD both below the median. Our results are consistent with an increasing body of evidence suggesting that vitamin D concentrations in early life may be associated with increased risk of neurodevelopmental disorders including ASD.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.EURONEURO.2021.04.021
Abstract: Depression is associated with general medical conditions (GMCs), but it is not known if treatment-resistant depression (TRD) affects GMC risk and vice versa. We estimated bidirectional associations between TRD and GMCs (prior and subsequent). All in iduals aged 18-69 years, born and living in Denmark, with a first-time prescription for an antidepressant between 2005 and 2012 were identified in the Danish Prescription Registry (N = 154,513). TRD was defined as at least two shifts in treatment regimes. For prior GMCs, we estimated odds ratios (ORs) using conditional logistic regression comparing TRD patients with matched non-TRD controls adjusted for other GMCs and number of other GMCs. For subsequent GMCs, we used Cox regression to calculate hazard ratios (HRs) in TRD vs. non-TRD patients adjusted for age at first prescription, calendar time, other GMCs and number of other GMCs. Patients with TRD had higher prevalence of prior GMCs related to the immune or neurological systems musculoskeletal disorders (women aOR: 1.35, 95% CI: 1.26-1.46, men aOR: 1.30, 95% CI: 1.19-1.42) and migraine (women aOR: 1.22, 95% CI: 1.09-1.36, men aOR: 1.25, 95% CI: 1.00-1.56). Subsequent GMCs were related to a broader spectrum cardiovascular (women aHR: 1.43, 95% CI: 1.32-1.54, men aHR: 1.31, 95% CI: 1.19-1.43), endocrine (women aHR: 1.52, 95% CI: 1.37-1.67, men aHR: 1.24, 95% CI: 1.07-1.44), and neurological disorders (women aHR: 1.24, 95% CI: 1.13-1.35, men aHR: 1.19, 95% CI: 1.07-1.34). Our study presents a broad overview of comorbid medical conditions in patients with TRD and further studies are needed to explore the associations in detail.
Publisher: Wiley
Date: 21-01-2016
DOI: 10.1111/PAI.12530
Abstract: Exposure to low levels of vitamin D in fetal life might affect the developing immune system, and subsequently the risk of childhood eczema. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with the risk of eczema until the age of 4 years. In a population-based prospective cohort study of 3019 mothers and their children, maternal blood s les in mid-gestation and umbilical cord blood s les at birth were used to determine 25-hydroxyvitamin D levels (severely deficient 1 year only), and persistent eczema (age ≤ and >1 year). Data were assessed using the generalized estimating equations and multinomial regression models. Compared with the optimal 25-hydroxyvitamin D group, sufficient, deficient, and severely deficient groups of 25-hydroxyvitamin D level in mid-gestation were not associated with the risk of overall eczema (odds ratios [95% confidence interval]: 1.09 [0.82, 1.43], 1.04 [0.87, 1.25], and 0.94 [0.81, 1.10], p-values for trend >0.05), nor with eczema per year or eczema patterns in children up to the age of 4 years. Similarly, we observed no associations of 25-hydroxyvitamin D groups at birth with any eczema outcome. Our results suggest that levels of 25-hydroxyvitamin D in mid-gestation and at birth are not associated with the risk of overall eczema, eczema per year, or eczema patterns among children until the age of 4 years.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2023
DOI: 10.1038/S41467-023-40330-W
Abstract: The predictive performance of polygenic scores (PGS) is largely dependent on the number of s les available to train the PGS. Increasing the s le size for a specific phenotype is expensive and takes time, but this s le size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to in idually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R 2 increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.SCHRES.2005.07.017
Abstract: The 'season of birth' effect is one of the most consistently replicated associations in schizophrenia epidemiology. In contrast, the association between season of birth and development in the general population is relatively poorly understood. The aim of this study was to explore the impact of season of birth on various anthropometric and neurocognitive variables from birth to age seven in a large, community-based birth cohort. A s le of white singleton infants born after 37 weeks gestation (n = 22,123) was drawn from the US Collaborative Perinatal Project. Anthropometric variables (weight, head circumference, length/height) and various measures of neurocognitive development, were assessed at birth, 8 months, 4 and 7 years of age. Compared to summer/autumn born infants, winter/spring born infants were significantly longer at birth, and at age seven were significantly heavier, taller and had larger head circumference. Winter/spring born infants were achieving significantly higher scores on the Bayley Motor Score at 8 months, the Graham-Ernhart Block Test at age 4, the Wechsler Intelligence Performance and Full Scale scores at age 7, but had significantly lower scores on the Bender-Gestalt Test at age 7 years. Winter/spring birth, while associated with an increased risk of schizophrenia, is generally associated with superior outcomes with respect to physical and cognitive development.
Publisher: Public Library of Science (PLoS)
Date: 04-04-2016
Publisher: SAGE Publications
Date: 2009
DOI: 10.1080/00048670802534333
Abstract: Objective: While birth cohort studies have shown that in iduals who develop non-affective psychosis show subtle deviations in cognitive and behavioural developmental trajectories, there is less evidence about deviations in physical growth in these in iduals. The purpose of the present study was to examine the association between behaviour and growth and maturation from infancy, through childhood and adolescence to early adulthood and the development of non-affective psychosis in young adults. Method: Based on a birth cohort of 3801 young adults, weight and length/height were examined at birth and at years 5, 14 and 21, together with pubertal maturation at year 14. Behavioural measures taken at years 5 and 14 were also examined. Screen-positive non-affective psychosis (SP-NAP) was assessed at year 21 using Composite International Diagnostic Interview, or a self-report checklist. The association between the behavioural and growth measures at birth and at years 5, 14 and 21, and SP-NAP at year 21 was examined using logistic regression. Results: There were 60 subjects in the cohort who were classified as having SP-NAP. In female subjects SP-NAP was significantly associated with being longer with a larger head circumference at birth, and less likely to be associated with being shorter at 21 years, with consistent trend associations for height between. There were no differences for weight. There was no significant association between the variables of interest in male subjects or for the total group. There was also no significant association between pubertal development at age 14 and risk of SP-NAP in either sex. Conclusions: Unlike developmental behavioural problems, which showed continuity from childhood through adolescence, SP-NAP was not associated with marked deviations in growth trajectory for male subjects, but the present data suggests that female subjects with SP-NAP had an altered skeletal growth trajectory.
Publisher: SAGE Publications
Date: 29-04-2013
Abstract: Because comorbidity between mental and physical disorders is commonly found in patients, it would be expected that this pattern would also be reflected at the family level. During a recent population-based survey of common mental disorders, respondents were asked about the presence of selected mental and physical disorders in their relatives. The aim of this research was to describe the within-family co-occurrence of selected common physical and mental disorders in a population-based s le. Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. A modified version of the World Mental Health Survey Initiative of the Composite International Diagnostic Interview (WMH-CIDI 3.0, henceforth CIDI) was used to identify lifetime-ever common psychiatric disorders (anxiety disorders, depression, drug or alcohol disorders). The respondents were asked if any of their relatives had one of a list of psychiatric (anxiety, bipolar disorder, depression, drug or alcohol problem, schizophrenia) or general physical disorders (cancer, heart problems, intellectual disability, memory problems). We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors. Compared to otherwise-well respondents, those who had a CIDI diagnosis of major depressive disorders, anxiety disorders, or drug or alcohol abuse/dependence were significantly more likely to have first-degree relatives with (a) the same diagnosis as the respondent, (b) other mental disorders not identified in the respondent, and (c) a broad range of general physical conditions. In iduals with common mental disorders report greater familial co-occurrence for a range of mental and physical disorders. When eliciting family histories, clinicians should remain mindful that both mental and physical disorders can co-occur within families.
Publisher: SAGE Publications
Date: 02-2003
DOI: 10.1046/J.1440-1614.2003.01106.X
Abstract: Background: Previous research into age of onset in affective disorders has produced conflicting results. This paper examines the influence of heterogeneity on the age-at-firstregistration distribution for the ICD-9 diagnostic group ‘affective psychosis’. Method: For 1979–1991, data for age-at-first-registration for 4985 in iduals diagnosed with affective psychosis (ICD-9 296.x) were extracted from a name-linked mental health register. These data were ided into (i) ‘296.1 only’, a category used to code unipolar depression (males = 700 females = 1321) and (ii) ‘296 other’, all 296 cases other than 296.1 (males = 1280 females = 1684). Inception rates for each 5-year age ision were adjusted for the background population age-structure as a rate per 100 000 population. Results: The age-at-first-registration distribution for affective psychosis has a wide age range, with women outnumbering men. There is a near-linear increase in inception rates for both men and women with 296.1 only, while the bulk of those with affective psychoses (296 other) have an inverted U-shaped age distribution. Males have an earlier modal age-atfirst-registration for 296 other compared to females. Conclusion: The heterogeneity in terms of subtypes and sex in affective psychosis clouds the interpretation of age-at-first-registration. Separating those with unipolar psychotic depression from other subclassifications and differentiating by sex may provide clues to factors that precipitate the onset of affective psychosis.
Publisher: Cambridge University Press (CUP)
Date: 04-07-2016
DOI: 10.1017/THG.2016.50
Abstract: Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable) and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair s les from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism ( r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC .36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger s le but raise the interesting question of the direction of causation between these variables.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.SCHRES.2021.06.004
Abstract: Over the last half century, a body of convergent evidence has accumulated linking disruption of early brain development with an increased risk of mental disorders, including schizophrenia. The orderly cascade of brain development may be disrupted by exposure to suboptimal concentrations of a range of biological substrates and micronutrients. We hypothesized that those exposed to vitamin D deficiency during early life, have an increased risk of neurodevelopmental disorders, including schizophrenia. The hypothesis was based on the link between an increased risk of schizophrenia in (a) those born in winter and spring, when vitamin D deficiency is more prevalent, and (b) the offspring of dark-skinned migrants living in cold climates, who have a markedly increased risk of vitamin D deficiency. In this review, we summarize evidence from analytic epidemiology related to this hypothesis. Two case-control studies based on Danish neonatal dried blood spots have found that neonatal vitamin deficiency is associated with an increased risk of schizophrenia. However, recent genetic analyses have also suggested that common variants linked to schizophrenia may lead to lower vitamin D concentrations (possibly mediated via reduced outdoor activity). We summarize limitations of the current evidence and outline suggestions that can guide future research. Based on currently available data, there is insufficient evidence to support public health recommendations related to this topic. However, we cannot reject the hypothesis that the provision of vitamin D supplementation to pregnant women and/or offspring in groups vulnerable to vitamin D deficiency may subsequently reduce the incidence of schizophrenia in the offspring.
Publisher: American Medical Association (AMA)
Date: 2021
DOI: 10.1001/JAMAPSYCHIATRY.2020.3049
Abstract: Polygenic risk scores (PRS) are predictors of the genetic susceptibilities of in iduals to diseases. All in iduals have DNA risk variants for all common diseases, but genetic susceptibility differences between people reflect the cumulative burden of these. Polygenic risk scores for an in idual are calculated as weighted counts of thousands of risk variants that they carry, where the risk variants and their weights have been identified in genome-wide association studies. Here, we review the underlying basic science of PRS, providing a foundation for understanding the potential clinical utility and limitations of PRS. Polygenic risk scores can be calculated for a wide range of diseases from a saliva or blood s le using genotyping technologies that are inexpensive. While genotyping only needs to be done once for each in idual in their lifetime, the PRS can be recalculated as identification of risk variants improves. On their own, PRS will never be able to establish or definitively predict future diagnoses of common complex conditions because genetic factors only contribute part of the risk, and PRS will only ever capture part of the genetic contributions. Nonetheless, just as clinical medicine uses a multitude of other predictive measures, PRS either on their own or as part of multivariable predictive algorithms could play a role. Utility of PRS in clinical medicine and ethical issues related to their use should be evaluated in the context of realistic expectations of what PRS can and cannot deliver. For different diseases, PRS could have utility in community settings (stratification to better triage people into established screening programs) or could contribute to clinical decision-making for those presenting with symptoms but where formal diagnosis is unclear. In principle, PRS could contribute to treatment choices, but more data are needed to allow development of PRS in this context.
Publisher: Wiley
Date: 22-08-2013
DOI: 10.1111/APPY.12093
Publisher: Wiley
Date: 24-03-2007
DOI: 10.1016/J.IJDEVNEU.2007.03.006
Abstract: Evidence is accumulating that normal levels of vitamin D are important for brain development. Vitamin D acts as an anti-proliferative agent in a wide variety of tissues and developmental vitamin D (DVD) deficiency has been shown to alter brain structure and function. The aim of this study was to investigate the effect of DVD deficiency on neuroprogenitor formation in the neonatal brain. We show that DVD deficiency increased the number of neurospheres formed in cultures from the neonatal subventricular zone. Exogenous vitamin D added to the culture medium reduced neurosphere number in control but not DVD cultures. We show the receptor for vitamin D is concentrated in the subventricular zone and is also present in cultured neurospheres prepared from this region. These results show that vitamin D can regulate cell proliferation in the developing brain. Further studies are warranted to examine the underlying mechanisms for these findings.
Publisher: American Medical Association (AMA)
Date: 02-2021
DOI: 10.1001/JAMAPSYCHIATRY.2020.3042
Abstract: Polygenic risk scores (PRS) are predictors of the genetic susceptibility to diseases, calculated for in iduals as weighted counts of thousands of risk variants in which the risk variants and their weights have been identified in genome-wide association studies. Polygenic risk scores show promise in aiding clinical decision-making in many areas of medical practice. This review evaluates the potential use of PRS in psychiatry. On their own, PRS will never be able to establish or definitively predict a diagnosis of common complex conditions (eg, mental health disorders), because genetic factors only contribute part of the risk and PRS will only ever capture part of the genetic contribution. Combining PRS with other risk factors has potential to improve outcome prediction and aid clinical decision-making (eg, determining follow-up options for in iduals seeking help who are at clinical risk of future illness). Prognostication of adverse physical health outcomes or response to treatment in clinical populations are of great interest for psychiatric practice, but data from larger s les are needed to develop and evaluate PRS. Polygenic risk scores will contribute to risk assessment in clinical psychiatry as it evolves to combine information from molecular, clinical, and lifestyle metrics. The genome-wide genotype data needed to calculate PRS are inexpensive to generate and could become available to psychiatrists as a by-product of practices in other medical specialties. The utility of PRS in clinical psychiatry, as well as ethical issues associated with their use, should be evaluated in the context of realistic expectations of what PRS can and cannot deliver. Clinical psychiatry has lagged behind other fields of health care in its use of new technologies and routine clinical data for research. Now is the time to catch up.
Publisher: Elsevier BV
Date: 1998
Publisher: BMJ
Date: 03-2018
DOI: 10.1136/BMJOPEN-2017-021000
Abstract: Clozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation. A 24-week double-blind placebo-controlled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining % body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants. Ethics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds. ACTRN12617001547336 Pre-results.
Publisher: SAGE Publications
Date: 23-03-2015
Publisher: Royal College of Psychiatrists
Date: 12-1995
Abstract: To assess quarterly fluctuations in schizophrenia births in a southern hemisphere data set, and to compare the quarterly birth distributions of patients born in the northern and southern hemisphere. The month and place of birth of patients with schizophrenia ( n = 9348) were extracted from a mental health register. The quarterly birth distribution of patients with schizophrenia differed significantly from the estimated general population distribution in SH-born patients. The quarterly distribution of patient births differed significantly when the two hemispheres were compared. These data support the hypothesis that there is a risk for schizophrenia that is related to the time of birth, and which fluctuates across the year.
Publisher: CMA Joule Inc.
Date: 27-09-2005
DOI: 10.1503/CMAJ.1050100
Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1016/S0920-9964(01)00259-6
Abstract: Based on the well-described excess of schizophrenia births in winter and spring, we hypothesised that in iduals with schizophrenia (a) would be more likely to be born during periods of decreased perinatal sunshine, and (b) those born during periods of less sunshine would have an earlier age of first registration. We undertook an ecological analysis of long-term trends in perinatal sunshine duration and schizophrenia birth rates based on two mental health registers (Queensland, Australia n=6630 The Netherlands n=24,474). For each of the 480 months between 1931 and 1970, the agreement between slopes of the trends in psychosis and long-term sunshine duration series were assessed. Age at first registration was assessed by quartiles of long-term trends in perinatal sunshine duration. Males and females were assessed separately. Both the Dutch and Australian data showed a statistically significant association between falling long-term trends in sunshine duration around the time of birth and rising schizophrenia birth rates for males only. In both the Dutch and Australian data there were significant associations between earlier age of first registration and reduced long-term trends in sunshine duration around the time of birth for both males and females. A measure of long-term trends in perinatal sunshine duration was associated with two epidemiological features of schizophrenia in two separate data sets. Exposures related to sunshine duration warrant further consideration in schizophrenia research.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.YFRNE.2012.07.001
Abstract: Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimer's disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus.
Publisher: SAGE Publications
Date: 03-1982
DOI: 10.3109/00048678209159469
Abstract: One hundred and seventy-eight subjects completed a questionnaire regarding ECT. The s le comprised three groups of approximately equal size: a group of patients who had received ECT, a group of visitors to ECT-treated psychiatric patients, and a group of visitors to non-ECT-treated psychiatric patients. Misconceptions about ECT were common throughout, particularly in the young, those giving films and television as a source of information and those visiting patients not receiving ECT. Fewer misconceptions occurred among those who were more highly educated or had experience of ECT either personally or via a visited friend or relative. Less fear of the procedure was expressed by those given the treatment and those who had the treatment explained to them by a doctor. Over half of the patient group denied having had ECT explained to them.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.BIOPSYCH.2018.04.012
Abstract: Studies have suggested that poor school achievement is associated with increased risk of schizophrenia however, the possible genetic contribution to this association is unknown. We investigated the possible effect of the polygenic risk score (PRS) for schizophrenia (PRS We conducted a case-cohort study on a Danish population-based s le born from 1987 to 1995 comprising 1470 in iduals with schizophrenia and 7318 subcohort noncases. Genome-wide data, school performance, and family psychiatric and socioeconomic background information were obtained from national registers and neonatal biobanks. PRS Higher PRS The current PRS did not account for the observed association between primary school performance and risk of schizophrenia.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
DOI: 10.1038/S41398-019-0626-Z
Abstract: Schizophrenia has been associated with a range of genetic and environmental risk factors. Here we explored a link between two risk factors that converge on a shared neurobiological pathway. Recent genome-wide association studies (GWAS) have identified risk variants in genes that code for L-type voltage-gated calcium channels (L-VGCCs), while epidemiological studies have found an increased risk of schizophrenia in those with neonatal vitamin D deficiency. The active form of vitamin D (1,25(OH) 2 D) is a secosteroid that rapidly modulates L-VGCCs via non-genomic mechanisms in a range of peripheral tissues, though its non-genomic effects within the brain remain largely unexplored. Here we used calcium imaging, electrophysiology and molecular biology to determine whether 1,25(OH) 2 D non-genomically modulated L-VGCCs in the developing prefrontal cortex, a region widely implicated in schizophrenia pathophysiology. Wide-field Ca 2+ imaging revealed that physiological concentrations of 1,25(OH) 2 D rapidly enhanced activity-dependent somatic Ca 2+ levels in a small subset of neurons in the developing PFC, termed vitamin D-responsive neurons (VDRNs). Somatic nucleated patch recordings revealed a rapid, 1,25(OH) 2 D-evoked increase in high-voltage-activated (HVA) Ca 2+ currents. Enhanced activity-dependent Ca 2+ levels were mediated by L-VGCC but not associated with any changes to Cacna1c (L-VGCC pore-forming subunit) mRNA expression. Since L-VGCC activity is critical to healthy neurodevelopment, these data suggest that suboptimal concentrations of 1,25(OH) 2 D could alter brain maturation through modulation of L-VGCC signalling and as such may provide a parsimonious link between epidemiologic and genetic risk factors for schizophrenia.
Publisher: SAGE Publications
Date: 06-1999
Publisher: Elsevier BV
Date: 08-2008
Publisher: Elsevier BV
Date: 08-2006
Publisher: Elsevier BV
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 23-12-2015
Publisher: Cold Spring Harbor Laboratory
Date: 12-08-2022
DOI: 10.1101/2022.08.11.22278618
Abstract: Proportional hazards models have previously been proposed to analyse time-to-event phenotypes in genome-wide association studies(GWAS). While proportional hazards models have many useful applications, their ability to identify genetic associations under different generative models where ascertainment is present in the analysed data is poorly understood. This includes widely used study designs such as case-control and case-cohort designs (e.g. the iPSYCH study design) where cases are commonly ascertained. Here we examine how recently proposed and computationally efficient Cox regression for GWAS perform under different generative models with and without ascertainment. We also propose the age-dependent liability threshold model (ADuLT), first introduced as the underlying model for the LT-FH++ method, as an alternative approach for time-to-event GWAS. We then benchmark ADuLT with SPACox and standard case-control GWAS using simulated data with varying degrees of ascertainment. We find Cox regression GWAS to underperform when cases are strongly ascertained (cases are overs led by a factor larger than 5), regardless of the generative model used. In contrast, we found ADuLT to be robust to case-control ascertainment, while being much faster to run. We then used the methods to conduct GWAS for four psychiatric disorders, ADHD, Autism, Depression, and Schizophrenia in the iPSYCH case-cohort s le, which has a strong case-ascertainment. Summarising across all four mental disorders, ADuLT found 20 independent genome-wide significant associations, while case-control GWAS found 17 and SPACox found 8, consistent with our simulation results. As more genetic data are being linked to electronic health records, robust GWAS methods that can make use of age-of-onset information have the opportunity to increase power in analyses. We find that ADuLT to be a robust time-to-event GWAS method that performs on par with or better than Cox-regression GWAS, both in simulations and real data analyses of four psychiatric disorders. ADuLT has been implemented in an R package called LTFHPlus, and is available on GitHub.
Publisher: Royal College of Psychiatrists
Date: 07-10-2022
DOI: 10.1192/BJO.2022.583
Abstract: General medical conditions (GMCs) often co-occur with mental and substance use disorders (MSDs). To explore the contribution of GMCs to the burden of disease in people with MSDs, and investigate how this varied by age. A population-based cohort of 6 988 507 persons living in Denmark during 2000–2015 followed for up to 16 years. Danish health registers were used to identify people with MSDs and GMCs. For each MSD, years lived with disability and health loss proportion (HeLP) were estimated for comorbid MSDs and GMCs, using a multiplicative model for disability weights. Those with any MSD lost the equivalent of 43% of healthy life (HeLP = 0.43, 95% CI 0.40–0.44) after including information on GMCs, which was an increase from 25% before including GMCs (HeLP = 0.25, 95% CI 0.23–0.27). Schizophrenia was associated with the highest burden of disease (HeLP = 0.77, 95% CI 0.68–0.85). However, within each disorder, the relative contribution of MSDs and GMCs varied. For ex le, in those diagnosed with schizophrenia, MSDs and GMCs accounted for 86% and 14% of the total health loss in contrast, in those with anxiety disorders, the same proportions were 59% and 41%. In general, HeLP increased with age, and was mainly associated with increasing rates of pulmonary, musculoskeletal and circulatory diseases. In those with mental disorders, the relative contribution of comorbid GMCs to the non-fatal burden of disease increases with age. GMCs contribute substantially to the non-fatal burden of disease in those with MSDs.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2020
DOI: 10.1038/S41467-020-15421-7
Abstract: Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identify 143 independent loci in 112 1-Mb regions, providing insights into the physiology of vitamin D and implicating genes involved in lipid and lipoprotein metabolism, dermal tissue properties, and the sulphonation and glucuronidation of 25OHD. Mendelian randomization models find no robust evidence that 25OHD concentration has causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes have (direct or indirect) causal effects on 25OHD concentration, clarifying the epidemiological relationship between 25OHD status and the health outcomes examined in this study.
Publisher: Elsevier BV
Date: 12-1995
DOI: 10.1016/0920-9964(95)00016-X
Abstract: This study of patients with functional psychoses set out to examine associations between minor physical anomalies (MPAs) and demographic, clinical, CT scan measures, and putative aetiological variables. 157 psychotic patients had minor physical anomalies assessed using a modified Waldrop scale. RDC diagnoses for these patients were: schizophrenia (n = 79), schizoaffective disorder (n = 31), mania (n = 24), major depression (n = 13), unspecified functional psychosis (n = 8), other organic psychosis (n = 2). 63 healthy white controls were also assessed with the modified Waldrop scale. Minor physical anomalies were not associated with any particular diagnosis. For white subjects, patients had significantly more MPAs than well controls. Anomalies of the palate were the most frequent item reported in patients and controls. For males, there was a weak association between the presence of MPAs and positive family history of a major psychiatric disorder. Those with MPAs required more frequent and longer psychiatric admissions, and showed impaired ability on a test sensitive to left parietal system function. Within the patient group, there were no associations between MPAs and gender, age at onset, negative symptoms, premorbid level of functioning, estimated premorbid intelligence, pregnancy and birth complications, and selected CT variables. Minor physical anomalies are found in a range of functional psychoses. There may be overlap between the various genes that predispose to psychiatric illness (especially in males) and those genes that predispose to developmental instability.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S0165-1781(02)00036-7
Abstract: This study was designed to examine whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. Symptom dimension ratings were assigned to 52 outpatients with schizophrenia (ICD-10 criteria), using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. Severity of positive symptoms was uncorrelated with performance on any of the measures examined. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.
Publisher: Wiley
Date: 13-09-2018
DOI: 10.1111/EIP.12380
Abstract: To find factors that are associated with not having psychotic illness in a prospective general population s le, with a special interest in in iduals with parental psychosis. Data from the Northern Finland Birth Cohort 1966 (n = 10 458) and several registers were used to detect in iduals with and without parental psychosis. Altogether, 594 persons had parent(s) with psychosis and 48 of them also had psychosis subsequently. Variables related to pregnancy and birth, family and childhood, health and habits in adolescence, school performance and physical activity were studied to identify determinants of unaffected status among in iduals with and without parental psychosis. In the parental psychosis group, the unaffected persons had more likely a mother who was non-depressed during pregnancy, and who worked outside the home or studied than among those who developed psychosis. Protective factors for psychosis were surprisingly few in this s le. These factors were related to the mother's non-depressed mood and the mother's work outside the home or studies. This could relate to better health and functioning of a mother. This work highlights the need for more research on protective factors for psychosis in order to identify methods for prevention of psychosis.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.PSYCHRES.2017.02.029
Abstract: Disruptive behavior disorders (DBDs), inclusive of oppositional defiant disorder (ODD) and conduct disorder (CD), are associated with outcomes likely to increase risk of mortality. Using Danish National Registers, a total of 1.92 million in iduals including 9495 in iduals with DBDs diagnosed by specialist services were followed from their first birthday to 2013. Those with and without DBDs were compared using mortality rate ratios (MRRs) estimated using Poisson regression and adjusted for calendar period, age, sex, family history of psychiatric disorders, maternal age at time of birth, paternal age at time of birth, parental education status, and parental employment status. Over the course of follow up, which totalled 24.9 million person-years, 5580 cohort members died including 78 in iduals with DBDs. The mortality rate per 10,000 person-years was 9.66 for in iduals with DBDs compared to 2.22 for those with no diagnosis. This corresponded to a fully adjusted MRR of 2.57 (95% confidence interval 2.04-3.20). Comorbid substance use disorder and attention-deficit/hyperactivity disorder resulted in the highest MRR across all categories. These findings demonstrate the excess mortality associated with DBDs.
Publisher: BMJ
Date: 06-02-2019
DOI: 10.1136/BMJ.L94
Abstract: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Systematic analysis. Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Springer Science and Business Media LLC
Date: 24-05-2019
Publisher: Springer Science and Business Media LLC
Date: 22-08-2012
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.SCHRES.2018.09.021
Abstract: Loneliness is an established risk factor for poor cardiometabolic health. People with psychotic disorders experience high rates of both cardiometabolic disease and loneliness, but how these factors are associated is poorly understood. Thus, using data from the second Australian National Survey of Psychosis we examined whether loneliness is associated with the likelihood of cardiometabolic disorder in psychotic illness. Loneliness was assessed using a single-item measure, with a 4-point scale (not lonely lonely occasionally some friends but lonely for company socially isolated and lonely) whilst cardiometabolic status was assessed in terms of the criteria used to determine metabolic syndrome (elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose). Logistic regression was employed to examine whether loneliness was associated with metabolic syndrome status, and its in idual components, with and without adjustment for confounding variables. Increased loneliness was associated with an increased risk of metabolic syndrome in people with psychosis (OR 1.21, 95% CI 1.08-1.36, p < .001) and to the risk of elevated waist circumference (p < .01), elevated triglycerides (p < .05) and reduced high-density lipoprotein cholesterol (p < .05). Notably, these associations largely persisted when controlling for a range of covariates. Feeling lonely is significantly associated with metabolic syndrome, and dyslipidemia specifically, in people with psychotic disorders. These data suggest that the potential benefits of interventions to reduce loneliness in psychosis may extend to cardiovascular as well as psychosocial functioning, and should be explored in future research.
Publisher: Wiley
Date: 24-07-2015
Publisher: Elsevier BV
Date: 2017
Publisher: SAGE Publications
Date: 23-12-2014
Publisher: American Medical Association (AMA)
Date: 03-2014
DOI: 10.1001/JAMAPSYCHIATRY.2013.4081
Abstract: There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes. To determine the association between maternal and paternal age and a comprehensive range of mental health disorders. A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period. Maternal and paternal age at the time of offspring's birth. We examined a broad range of International Classification of Diseases-defined mental disorders, including substance use schizophrenia and related disorders mood disorders neurotic, stress-related, and somatoform disorders eating disorders specific personality disorders and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent. The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For ex le, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation. The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.
Publisher: Cold Spring Harbor Laboratory
Date: 14-11-2019
DOI: 10.1101/841452
Abstract: Principal Component Analysis (PCA) of genetic data is routinely used to infer ancestry and control for population structure in various genetic analyses. However, conducting PCA analyses can be complicated and has several potential pitfalls. These pitfalls include (1) capturing Linkage Disequilibrium (LD) structure instead of population structure, (2) projected PCs that suffer from shrinkage bias, (3) detecting s le outliers, and (4) uneven population sizes. In this work, we explore these potential issues when using PCA, and present efficient solutions to these. Following applications to the UK Biobank and the 1000 Genomes project datasets, we make recommendations for best practices and provide efficient and user-friendly implementations of the proposed solutions in R packages bigsnpr and bigutilsr. For ex le, we find that PC19 to PC40 in the UK Biobank capture complex LD structure rather than population structure. Using our automatic algorithm for removing long-range LD regions, we recover 16 PCs that capture population structure only. Therefore, we recommend using only 16-18 PCs from the UK Biobank to account for population structure confounding. We also show how to use PCA to restrict analyses to in iduals of homogeneous ancestry. Finally, when projecting in idual genotypes onto the PCA computed from the 1000 Genomes project data, we find a shrinkage bias that becomes large for PC5 and beyond. We then demonstrate how to obtain unbiased projections efficiently using bigsnpr. Overall, we believe this work would be of interest for anyone using PCA in their analyses of genetic data, as well as for other omics data.
Publisher: Wiley
Date: 06-2014
DOI: 10.1002/WPS.20130
Publisher: Springer Science and Business Media LLC
Date: 2002
DOI: 10.2165/00003495-200262050-00003
Abstract: Substance misuse in in iduals with schizophrenia is very common, especially in young men, in communities where use is frequent and in people receiving inpatient treatment. Problematic use occurs at very low intake levels, so that most affected people are not physically dependent (with the exception of nicotine). People with schizophrenia and substance misuse have poorer symptomatic and functional outcomes than those with schizophrenia alone. Unless there is routine screening, substance misuse is often missed in assessments. Service systems tend to be separated, with poor inter-communication, and affected patients are often excluded from services because of their comorbidity. However, effective management of these disorders requires a fully integrated approach because of the close inter-relationship of the disorders. Use of atypical antipsychotics may be especially important in this population because of growing evidence (especially on clozapine and risperidone) that nicotine smoking, alcohol misuse and possibly some other substance misuse is reduced. Several pharmacotherapies for substance misuse can be used safely in people with schizophrenia, but the evidence base is small and guidelines for their use are necessarily derived from experience in the general population.
Publisher: Public Library of Science (PLoS)
Date: 18-12-2013
Publisher: Elsevier BV
Date: 2023
Publisher: Springer Science and Business Media LLC
Date: 23-08-2019
DOI: 10.1007/S00127-019-01760-4
Abstract: We investigated if (a) people with lower physical activity have an increased risk of subsequent mental disorders (compared to those with higher physical activity) and (b) people with mental disorders have reduced subsequent physical activity (compared to those without mental disorders). A systematic review of population-based longitudinal studies examining physical activity and mental disorders was conducted. Mental disorders were defined by International Classification of Diseases or Diagnostic and Statistical Manual of Mental Disorders. The results were described in a narrative summary. Twenty-two studies were included. The majority (19) examined mood disorders and physical activity. Only two studies found consistent association between lower physical activity and a reduced risk of subsequent mental disorders. One study found the bidirectional association between physical activity and major depression. Twelve studies found mixed results (i.e., no consistency in direction and significance of the findings), and seven studies found no association between the variables of interest. There is a lack of consistent evidence linking physical activity to be either a risk factor or consequence of mental disorders. CRD42017071737.
Publisher: Elsevier BV
Date: 1992
Publisher: Springer Science and Business Media LLC
Date: 11-1994
Abstract: A pyridinium metabolite (HPP+) of the neuroleptic drug haloperidol has been identified in rats and in the urine of patients. The purpose of this study was to measure the steady-state blood and plasma concentrations and daily urinary excretion of HPP+ in patients treated with haloperidol. HPP+ was measured by HPLC with fluorescence detection. The chromatograms also revealed the presence of a previously unknown pyridinium species, which was identified in urine by liquid chromatography/mass spectrometry/mass spectrometry as 4-(4-chlorophenyl)-1-4-(4-fluorophenyl)-4-hydroxybutylpyridinium (RHPP+). Concentrations of RHPP+ were then measured by HPLC. The steady-state concentrations of HPP+ or RHPP+ in blood and plasma from 34 patients were virtually identical. The plasma concentrations of each metabolite were related to the daily dose of haloperidol and to its plasma concentrations. Nonlinearity in the elimination of RHPP+ was suggested by the increase in the ratio between RHPP+ and HPP+ plasma concentrations with dose or steady-state concentrations of haloperidol. The concentrations of RHPP+ in plasma and urine generally exceeded those of HPP+ the ratio between them in plasma ranged from 0.9 to 14.1. The daily urinary excretion of HPP+ and RHPP+ accounted for 0.40% +/- 0.18% and 2.3% +/- 1.4% of the haloperidol dose, respectively. The renal clearance of each species was 4.5 +/- 2.5 and 11.3 +/- 5.3 L/hr, respectively. The presence of these pyridinium species in humans raises the concern that they may be neurotoxic in a manner similar to the dopaminergic pro-neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Publisher: American Medical Association (AMA)
Date: 11-2019
Publisher: Elsevier BV
Date: 06-1996
DOI: 10.1016/S0140-6736(96)91525-1
Abstract: Mangrove ecosystems have been the focus of global attention for their crucial role in sheltering coastal communities and retarding global climate change by sequestering 'blue carbon'. China is relatively rich in mangrove ersity, with one-third of the ca. 70 true mangrove species and a number of mangrove associate species occurring naturally along the country's coasts. Mangrove ecosystems, however, are widely threatened by intensifying human disturbances and rising sea levels. DNA barcoding technology may help protect mangrove ecosystems by providing rapid species identification. To investigate this potential, 898 plant specimens were collected from 33 major mangrove sites in China. Based on the morphologic diagnosis, the specimens were assigned to 72 species, including all 28 true mangrove species and all 12 mangrove associate species recorded in China. Three chloroplast DNA markers rbcL, trnH-psbA, matK, and one nuclear marker ITS2 were chosen to investigate the utility of using barcoding to identify these species. According to the criteria of barcoding gaps in genetic distance, sequence similarity, and phylogenetic monophyly, we propose that a single marker, ITS2, is sufficient to barcode the species of mangroves and their associates in China. Furthermore, rbcL or trnH-psbA can also be used to gather supplement confirming data. In using these barcodes, we revealed a very low level of genetic variation among geographic locations in the mangrove species, which is an alert to their vulnerability to climate and anthropogenic disturbances. We suggest using ITS2 to barcode mangrove species and terrestrial coastal plants in South China. The DNA barcode sequences we obtained would be valuable in monitoring bio ersity and the restoration of ecosystems, which are essential for mangrove conservation.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 18-11-2020
DOI: 10.1111/DAR.13217
Publisher: SAGE Publications
Date: 03-07-2012
Abstract: To determine the prevalence of cardiometabolic risk factors in Australian adults with a psychotic disorder. Data were collected during the interview phase of the second Australian survey of psychosis, a population-based survey of Australians aged 18 to 64 years with a psychotic disorder. Body mass index, waist circumference and blood pressure were measured. Participants were asked about diagnoses of relevant medical conditions, medications, smoking and physical activity. Fasting blood s les were analysed for glucose, high-density lipoprotein cholesterol, total cholesterol and triglycerides. The prevalence of metabolic syndrome was determined using the harmonized criteria developed by the International Diabetes Federation and other bodies. A total of 1087 men (60%) and 738 women (40%) participated. Their mean age was 38.36 (SD 11.16) years 773 (42%) were aged 18–34 years and 1052 (58%) 35–64 years. Three-quarters were overweight or obese and 82% had abdominal obesity. Almost half were hypertensive. Two-thirds were current smokers and 81% had a lifetime history of smoking. Levels of physical activity were very low. About 30% reported a diagnosis of hypertension or high cholesterol, 20% knew they had diabetes or high blood sugar and 18% had cardiovascular disease. Half of those with self-reported hypertension were taking antihypertensive drugs, and about 40% with hypercholesterolemia or hyperglycaemia were receiving medication for these conditions. Seventy per cent ( N = 1286) of participants provided fasting blood s les. Abnormal levels of high-density lipoprotein cholesterol and triglycerides were each found in almost half of participants and almost one-third had elevated fasting glucose. More than half of participants (54.8%) met criteria for metabolic syndrome. Australians living with psychosis have high rates of cardiometabolic risk factors. There are a number of obvious targets for prevention and treatment, including obesity (especially in women), smoking (more prevalent in men), hypertension, hyperlipidaemia and sedentary lifestyle.
Publisher: Springer Science and Business Media LLC
Date: 08-11-2017
Publisher: Elsevier BV
Date: 07-2008
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.NEUROSCIENCE.2013.01.035
Abstract: There is growing evidence that vitamin D is a neuroactive steroid capable of regulating multiple pathways important for both brain development and mature brain function. In particular, there is evidence from rodent models that prenatal vitamin D deficiency alters the development of dopaminergic pathways and this disruption is associated with altered behavior and neurochemistry in the adult brain. Although the presence of the vitamin D receptor (VDR) has been noted in the human substantia nigra, there is a lack of direct evidence showing that VDR is present in dopaminergic cells. Here we confirm that the VDR is present in the nucleus of tyrosine hydroxylase (TH)-positive neurons in both the human and rat substantia nigra, and it emerges early in development in the rat, between embryonic day 12 (E12) and E15. Consistent evidence based on immunohistochemistry, real-time PCR and western blot confirmed a pattern of increasing VDR expression in the rat midbrain until weaning. The nuclear expression of VDR in TH-positive neurons during critical periods of brain development suggests that alterations in early life vitamin D status may influence the orderly development of dopaminergic neurons.
Publisher: SAGE Publications
Date: 06-10-2022
DOI: 10.1177/00048674221129184
Abstract: The aim of the study was to estimate the annual health care cost by number of comorbid mental and somatic disorders in persons with a mental disorder. All persons living in Denmark between 2004 and 2017 with a hospital diagnosis of a mental disorder were identified. We investigated the cost of different health care services: psychiatric hospitals, somatic hospitals, primary health care (e.g. general practitioners, psychologists and so on) and subsidised prescriptions. Within those with at least one mental disorder, we examined the costs for people with (a) counts of different types of mental disorders (e.g. exactly 1, exactly 2 and so on up to 8 or more) and (b) counts of different types of somatic disorders (e.g. no somatic disorders, exactly 1, exactly 2 and so on up to 15 or more). The estimates are reported in average cost per case and nationwide annual cost in Euro 2017. In total, 447,209 persons (238,659 females and 208,550 males) were diagnosed with at least one mental disorder in the study period. The average annual health care cost per case and nationwide cost was 4471 Euros and 786 million Euro, respectively, for persons with exactly one mental disorder, and 33,273 Euro and 3.6 million Euro for persons with eight or more mental disorders. The annual health care cost was 4613 Euro per case and 386 million Euro for persons without any somatic disorders, while the cost per case was 16,344 Euro and 0.7 million Euro in nationwide cost for persons with 15 or more disorders. The amount and proportion of the different health care costs varied by type of comorbidity and count of disorders. The annual health care cost per case was higher with increasing number of comorbid mental and somatic disorders, while the nationwide annual health care cost was lower with increasing number of comorbid disorders for persons with a mental disorder in Denmark.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Springer Science and Business Media LLC
Date: 04-2007
DOI: 10.1007/S00406-007-0714-6
Abstract: To investigate the impact of parental disorder in the life of adult offspring by evaluating education, current employment and marital status of a s le of offspring of patients with schizophrenia and comparing findings with population rates. A s le of 489 patients with DSM-IV diagnoses of schizophrenia was identified in the public outpatient mental health services of the city of Cuiabá, Brazil. Of these patients, 294 had children, and a total of 828 offspring were identified. Data for 431 offspring aged 18 years or older were collected using a structured questionnaire answered by the patient-parent and a family member. The percentage of age-grade discrepancy for offspring aged 18 and 19 years was 59.2% (95%CI 45.4-73.0), not significantly different from the discrepancy rate for the same age group in the general population, which was 71.1%. Offspring of patients with schizophrenia had a significantly poorer employment situation than the general population (66.7% and 75.6% 95%CI 62.1-71.3). Fewer male offspring were married than males in the general population (54.7% and 66.0% 95%CI 48.2-61.2). Adult offspring of patients with schizophrenia had social adjustment problems that were markedly reflected in employment and marital status.
Publisher: Cambridge University Press (CUP)
Date: 03-12-2015
DOI: 10.1017/THG.2014.70
Abstract: Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population s le may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years standard deviation 0.25). Plasma cytokine measures were available for 400 in iduals (85 MZ, 115 DZ pairs), dried blood spot s le vitamin D measures were available for 378 in iduals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger s le sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2019
DOI: 10.1007/S10519-019-09954-X
Abstract: This study assessed the heritability of 25 hydroxyvitamin D
Publisher: Royal College of Psychiatrists
Date: 04-2007
DOI: 10.1192/BJP.BP.106.026708
Abstract: Surveys have found that otherwise well in iduals report delusional experiences. Previous studies have shown an association between psychotic symptoms and exposure to trauma. To explore the association between trauma and delusional experiences in a community s le. Respondents ( n = 10 641) were assessed for delusional experiences, exposure to various types of traumatic experiences and the presence of post-traumatic stress disorder (PTSD). The endorsement of delusional items was examined in people exposed to traumatic events who did or did not have PTSD. Exposure to any traumatic event but without the development of PTSD was associated with increased endorsement of delusional experiences (relative risk 2.68, 95% CI 2.18–3.30) and there was a significant dose–response relationship between the number of types of traumatic events and endorsement of such experiences (χ 2 =26.74, d.f. =2, P 0.001). A diagnosis of PTSD further increased endorsement of delusional experiences (RR = 9.24, 95% CI 6.95–12.27). The association between PTSD and delusional experiences remained significant after adjusting for factors associated with psychotic symptoms. Further investigation into the pathways between trauma, delusions and psychosis may provide insights into shared aetiological mechanisms underpinning these conditions.
Publisher: Wiley
Date: 25-05-2017
DOI: 10.1111/ACPS.12749
Abstract: While psychotic experiences ( PE s) are known to be associated with a range of mental and general medical disorders, little is known about the association between PE s and measures of disability. We aimed to investigate this question using the World Mental Health surveys. Lifetime occurrences of six types of PE s were assessed along with 21 mental disorders and 14 general medical conditions. Disability was assessed with a modified version of the WHO Disability Assessment Schedule. Descriptive statistics and logistic regression models were used to investigate the association between PE s and high disability scores (top quartile) with various adjustments. Respondents with PE s were more likely to have top quartile scores on global disability than respondents without PE s (19.1% vs. 7.5% χ 2 = 190.1, P 0.001) as well as greater likelihood of cognitive, social, and role impairment. Relationships persisted in each adjusted model. A significant dose–response relationship was also found for the PE type measures with most of these outcomes. Psychotic experiences are associated with disability measures with a dose–response relationship. These results are consistent with the view that PE s are associated with disability regardless of the presence of comorbid mental or general medical disorders.
Publisher: Elsevier BV
Date: 03-2002
Publisher: Wiley
Date: 18-02-2018
DOI: 10.1111/ACPS.12863
Abstract: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective s le (N = 6081) from the Northern Finland Birth Cohort 1986. Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05 1.01-1.08). Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.
Publisher: Hindawi Limited
Date: 22-11-2020
DOI: 10.1002/DA.23113
Publisher: Wiley
Date: 09-03-2018
DOI: 10.1111/ACPS.12865
Publisher: S. Karger AG
Date: 2014
DOI: 10.1159/000356498
Abstract: b i Background: /i /b There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ). b i Method: /i /b Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively. b i Results: /i /b The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92 95% confidence interval, CI: 0.87-0.98 I sup /sup = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80 95% CI: 0.75- 0.86 I sup /sup = 82.8%), and in those with AD (ES = 0.32 95% CI: 0.22-0.46 I sup /sup = 0.0%), PD (ES = 0.83 95% CI: 0.76-0.91 I sup /sup = 80.0%), MS (ES = 0.91 95% CI: 0.87-0.95 I sup /sup = 30.3%) and HD (ES = 0.53 95% CI: 0.42-0.67 I sup /sup = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46 95% CI: 1.08-1.96 I sup /sup = 87.9%). No association was observed between cancer and ALS (ES = 0.97 95% CI: 0.76-1.25 I sup /sup = 0.0%) or SCZ (ES = 0.98 95% CI: 0.90-1.07 I sup /sup = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD lung and prostate cancers in MS and melanoma and prostate cancer in SCZ). b i Conclusion: /i /b Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.
Publisher: Wiley
Date: 21-09-2017
DOI: 10.1002/WPS.20457
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.ARR.2017.12.002
Abstract: Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline.
Publisher: Elsevier BV
Date: 06-2004
Publisher: Wiley
Date: 04-08-2003
Abstract: Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.
Publisher: Elsevier BV
Date: 2000
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.SCHRES.2008.11.002
Abstract: There is an emerging interest in children and adolescents who have hallucinations and other psychotic-like experiences to enable identification of those potentially at risk for schizophrenia in adulthood. This study examines the prevalence, demographic and clinical correlates of hallucinations in the adolescent subgroup of the Australian National Survey of Mental Health and Well-Being. Participants were a nationally representative s le of 1261 adolescents aged 13-17 years. Adolescents completed self-report questionnaires with two questions relating to hallucinations and questions pertaining to depressive symptoms and cannabis use. Parents completed the Child Behavior Checklist (CBCL) and the Diagnostic Interview Schedule for Children (DISC-IV). Hallucinations were reported by 8.4% of adolescents. Those living in blended or sole parent families were more likely to report hallucinations than those living with both biological parents (OR 3.27 95% CI 1.93, 5.54 OR 2.60 95% CI 1.63, 4.13 respectively). Hallucinations were more prevalent in adolescents who scored in the highest decile of the CBCL or had elevated depression symptoms (OR 3.30 95% CI 2.10, 5.20 OR 5.02 95% CI 3.38, 7.45 respectively). Hallucinations were associated with depressive disorder (OR 2.70 95% CI 1.16, 6.28) and were more prevalent in those adolescents who had smoked cannabis more than twice in the month prior to the survey (OR 3.27 95% CI 1.76, 6.08). Hallucinations occur relatively frequently in adolescents and are associated with a range of demographic and clinical correlates. Further research may assist in understanding the variable trajectory of children and adolescents who hallucinate.
Publisher: Cambridge University Press (CUP)
Date: 09-01-2017
DOI: 10.1017/S0033291716003263
Abstract: Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the life-course and whether mental disorders that emerge prior to PEs explain these associations. We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models. Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9–2.6]. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6–20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF). Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.
Publisher: Wiley
Date: 04-08-2008
DOI: 10.1111/J.1600-0447.2008.01214.X
Abstract: Psychotic-like experiences (PLE) in the general community are common. The aims of this study were to examine the prevalence and demographic correlates of PLE in young adults. The s le consisted of 2441 subjects aged 18-23 years. Subjects completed the Composite International Diagnostic Interview (CIDI) and the 21-item Peters Delusional Inventory (PDI). Associations between age, gender, hallucinations and delusions were examined using logistic regression. Both CIDI hallucinations and delusions predicted high scores on the PDI. Younger age was significantly associated with endorsement of CIDI delusions [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.48-0.92) and with PDI total scores (OR = 0.68, 95% CI 0.55-0.83). Women were significantly more likely to endorse items related to hallucinations (OR = 1.49, 95% CI 1.14-1.95) but not delusions. PLE are common in young adults. The mechanisms underpinning the age and gender gradients in PLE may provide clues to the pathogenesis of psychotic disorders.
Publisher: Wiley
Date: 10-2005
DOI: 10.1111/J.1460-9568.2005.04355.X
Abstract: Insulin-like growth factor-I (IGF-I) has multiple effects within the developing nervous system but its role in neurogenesis in the adult nervous system is less clear. The adult olfactory mucosa is a site of continuing neurogenesis that expresses IGF-I, its receptor and its binding proteins. The aim of the present study was to investigate the roles of IGF-I in regulating proliferation and differentiation in the olfactory mucosa. The action of IGF-I was assayed in serum-free culture combined with bromodeoxyuridine-labelling of proliferating cells and immunochemistry for specific cell types. IGF-I and its receptor were expressed by globose basal cells (the neuronal precursor) and by olfactory neurons. IGF-I reduced the numbers of proliferating neuronal precursors, induced their differentiation into neurons and promoted morphological differentiation of neurons. The evidence suggests that IGF-I is an autocrine and/or paracrine signal that induces neuronal precursors to differentiate into olfactory sensory neurons. These effects appear to be similar to the cellular effects of IGF-I in the developing nervous system.
Publisher: Cambridge University Press (CUP)
Date: 29-09-2006
DOI: 10.1017/S0033291705005969
Abstract: Background. We describe the development, reliability and applications of the Diagnostic Interview for Psychoses (DIP), a comprehensive interview schedule for psychotic disorders. Method. The DIP is intended for use by interviewers with a clinical background and was designed to occupy the middle ground between fully structured, lay-administered schedules, and semi-structured, psychiatrist-administered interviews. It encompasses four main domains: ( a ) demographic data ( b ) social functioning and disability ( c ) a diagnostic module comprising symptoms, signs and past history ratings and ( d ) patterns of service utilization and patient-perceived need for services. It generates diagnoses according to several sets of criteria using the OPCRIT computerized diagnostic algorithm and can be administered either on-screen or in a hard-copy format. Results. The DIP proved easy to use and was well accepted in the field. For the diagnostic module, inter-rater reliability was assessed on 20 cases rated by 24 clinicians: good reliability was demonstrated for both ICD-10 and DSM-III-R diagnoses. Seven cases were interviewed 2–11 weeks apart to determine test–retest reliability, with pairwise agreement of 0·8–1·0 for most items. Diagnostic validity was assessed in 10 cases, interviewed with the DIP and using the SCAN as ‘gold standard’: in nine cases clinical diagnoses were in agreement. Conclusions. The DIP is suitable for use in large-scale epidemiological studies of psychotic disorders, as well as in smaller studies where time is at a premium. While the diagnostic module stands on its own, the full DIP schedule, covering demography, social functioning and service utilization makes it a versatile multi-purpose tool.
Publisher: Elsevier BV
Date: 09-2012
Publisher: Wiley
Date: 20-05-2003
DOI: 10.1002/AJMG.B.20059
Abstract: A single nucleotide polymorphism (TNF(-308A)) within the promoter region of the gene encoding tumor necrosis factor (TNF), has been significantly associated with schizophrenia in a study of Italian patients and control subjects Boin et al. [2001: Mol Psychiatry 6:79-82]. We have applied case-control analyses to examine TNF promoter haplotypes (containing TNF(-308) and two additional promoter variants: TNF(-376) and TNF(-238)) in four schizophrenia cohorts drawn from Australian, Indian Fijian, Indigenous Fijian, and Brahmin populations. In addition, we have applied the sibling transmission disequilibrium (STD) test to promoter haplotypes within 81 trios drawn from Australian Caucasian pedigrees with multiple schizophrenia cases, and 86 trios drawn from the Brahmin population of Tamil Nadu province in Southern India. Within each of these cohorts, we found no evidence of recombination between these tightly linked promoter variants, supporting previous studies which demonstrated that only a subset of the eight possible haplotypes exist. Of the four observed haplotypes, we and others have observed only one carries the TNF(-308A) variant allele. We report no significant differences in TNF promoter haplotype frequencies between the patient and control groups within each population, although the Indian Fijian cohort showed a trend towards reduced TNF(-308A) alleles amongst schizophrenia cases (P = 0.07). We found no evidence of bias in TNF promoter haplotype transmission to schizophrenia probands. Very similar results were obtained when only the TNF(-308) polymorphism was considered. Taken together, these data provide no support for the involvement of TNF promoter variants TNF(-308), TNF(-376), and TNF(-238) in schizophrenia susceptibility within four ethnically distinct cohorts.
Publisher: Springer Science and Business Media LLC
Date: 07-2023
Publisher: SAGE Publications
Date: 03-1989
DOI: 10.3109/00048678909062594
Abstract: Recent developments in molecular genetics are examined with particular reference to psychiatry. the new technologies available have allowed significant advances in the understanding of certain illnesses such as familial Alzheimer's disease and Huntington's chorea, and will provide powerful tools to explore many other important psychiatric illnesses. the area of genetic counselling is already characterized by complex ethical issues. We can expect that as the new technologies provide the prospect of positive germ line genetic engineering, these ethical issues will become more complex. It is important that psychiatrists prepare themselves for these future developments and take an active role in leading the debate.
Publisher: Wiley
Date: 21-09-2019
DOI: 10.1111/MCN.12672
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.SCHRES.2016.06.009
Abstract: Hallucinations, once equated with serious mental disorders, are common in adolescents. Given the high prevalence of hallucinations, it is important to determine if they are associated with adverse mental health outcomes in adulthood. This study compared the mental health outcomes of participants (aged 30-33years) in the Mater-University of Queensland Study of Pregnancy (MUSP) who reported hallucinations at (a) 14years only and (b) 14 and 21years versus cohort members without hallucinations. Participants (n=333) were aged between 30 and 33years and (a) reported hallucinations on the Youth Self-Report Questionnaire at 14 and/or the Young Adult Self-Report Questionnaire at 21years and (b) controls (n=321) who did not report hallucinations. Lifetime diagnoses of mental disorders were ascertained by the Structured Clinical Interview for DSM Disorders (DSM IV-TR) administered by clinical psychologists. Suicidal behaviour was measured by self report. Hallucinations at 14years only were not associated with an increased risk of mental disorders in adulthood. Hallucinations reported at both 14 and 21years were associated with lifetime diagnoses of psychotic disorders (OR, 8.84 95% CI: 1.61-48.43 and substance use disorders (OR, 2.34 95% CI: 1.36-4.07) and also strongly associated with lifetime suicide attempts (OR, 7.11 95% CI: 2.68-18.83). Most adolescents who experience hallucinations do not have an increased rate of mental disorder in adulthood however, those with hallucinations that are experienced at more than one point in time are at increased risk of suicidal behaviour and both psychotic and non-psychotic psychopathology.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.BBR.2012.12.001
Abstract: Epidemiological evidence suggests that low levels of vitamin D may predispose people to develop depression and cognitive impairment. While rodent studies have demonstrated that prenatal vitamin D deficiency is associated with altered brain development, there is a lack of research examining adult vitamin D (AVD) deficiency. The aim of this study was to examine the impact of AVD deficiency on behaviour and brain function in the mouse. Ten-week old male C57BL/6J and BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We assessed a broad range of behavioural domains, excitatory and inhibitory neurotransmission in brain tissue, and, in separate groups of mice, locomotor response to d- hetamine and MK-801. Overall, AVD deficiency resulted in hyperlocomotion in a novel open field and reduced GAD65/67 levels in brain tissue. AVD-deficient BALB/c mice had altered behaviour on the elevated plus maze, altered responses to heat, sound and shock, and decreased levels of glutamate and glutamine, and increased levels of GABA and glycine. By contrast C57BL/6J mice had a more subtle phenotype with no further behavioural changes but significant elevations in serine, homovanillic acid and 5-hydroxyindoleacetic acid. Although the behavioural phenotype of AVD did not seem to model a specific disorder, the overall reduction in GAD65/67 levels associated with AVD deficiency may be relevant to a number of neuropsychiatric conditions. This is the first study to show an association between AVD deficiency and prominent changes in behaviour and brain neurochemistry in the mouse.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.MCE.2017.05.035
Abstract: 1,25(OH)
Publisher: Elsevier BV
Date: 06-2016
Publisher: Springer Science and Business Media LLC
Date: 07-04-2017
Publisher: Elsevier BV
Date: 03-2003
Publisher: American Psychiatric Association Publishing
Date: 05-2009
DOI: 10.1176/APPI.AJP.2008.08081182
Abstract: Community surveys have shown that many otherwise well in iduals report delusional-like experiences. The authors examined psychopathology during childhood and adolescence as a predictor of delusional-like experiences in young adulthood. The authors analyzed prospective data from the Mater-University of Queensland Study of Pregnancy, a birth cohort of 3,617 young adults born between 1981 and 1983. Psychopathology was measured at ages 5 and 14 using the Child Behavior Checklist (CBCL) and at age 14 using the Youth Self-Report (YSR). Delusional-like experiences were measured at age 21 using the Peters Delusional Inventory. The association between childhood and adolescent symptoms and later delusional-like experiences was examined using logistic regression. High CBCL scores at ages 5 and 14 predicted high levels of delusional-like experiences at age 21 (odds ratios for the highest versus the other quartiles combined were 1.25 and 1.85, respectively). Those with YSR scores in the highest quartile at age 14 were nearly four times as likely to have high levels of delusional-like experiences at age 21 (odds ratio=3.71). Adolescent-onset psychopathology and continuous psychopathology through both childhood and adolescence strongly predicted delusional-like experiences at age 21. Hallucinations at age 14 were significantly associated with delusional-like experiences at age 21. The general pattern of associations persisted when adjusted for previous drug use or the presence of nonaffective psychoses at age 21. Psychopathology during childhood and adolescence predicts adult delusional-like experiences. Understanding the biological and psychosocial factors that influence this developmental trajectory may provide clues to the pathogenesis of psychotic-like experiences.
Publisher: Springer Science and Business Media LLC
Date: 15-01-2018
DOI: 10.1038/S41467-017-02317-2
Abstract: Health risk factors such as body mass index (BMI) and serum cholesterol are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. We develop and apply a method (called GSMR) that performs a multi-SNP Mendelian randomization analysis using summary-level data from genome-wide association studies to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height, and years of schooling (EduYears) with common diseases (s le sizes of up to 405,072). We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimer’s disease, and bidirectional associations with opposite effects (e.g., higher BMI increases the risk of T2D but the effect of T2D on BMI is negative).
Publisher: American Psychiatric Association Publishing
Date: 04-2014
DOI: 10.1176/APPI.PS.201300096
Abstract: Studies of the demographic and clinical correlates of employment activity have proven useful for identifying employment assistance needs among people with severe and persistent mental illness. However, the results of prior studies remain unclear, and most reviews of prior studies have not differentiated competitive from noncompetitive employment. This study attempted to clarify the relative strength and consistency of correlates of competitive versus noncompetitive employment. Data were drawn from a population-based survey of Australian adults with psychotic disorders between March and December 2010. Demographic, clinical, and employment assistance correlates of competitive and noncompetitive employment were compared. The s le comprised 1,825 participants who agreed to face-to-face interviews. A total of 408 (22.3%) participants were employed in the previous four weeks, 330 (18.1%) in competitive employment and 78 (4.3%) in noncompetitive employment. Those in competitive employment were more likely to be female and aged 18-34, to have a partner, to have received formal vocational training or education after high school, and to have no literacy difficulties. Better global functioning, shorter illness duration, less severe course of illness, and affective versus nonaffective psychosis were associated with a greater likelihood of competitive employment. Those using Australian government employment services were less likely to be in competitive employment, suggesting a service provider preference for noncompetitive employment. Four times as many employees were in competitive employment than in noncompetitive employment. The negative relationship between employment assistance and competitive employment highlights the urgent need to improve the effectiveness of Australian employment services for people with severe mental illnesses.
Publisher: Wiley
Date: 18-02-2022
DOI: 10.1111/ACPS.13410
Abstract: Information on mental disorders over time is critical for documenting changes in population burden, and aiding understanding of potential causal and non‐causal factors. The aim of this study was to provide temporal changes in the sex‐ and age‐specific incidence rates (IR) of mental disorders diagnosed in Danish hospitals during five decades and investigate whether such changes may be attributable to changes in administrative reporting practice. This population‐based cohort study included all people living in Denmark between 1970 and 2016. Mental disorders diagnoses were obtained from the Danish Psychiatric Central Research Register. We estimated the IR of each mental disorder (all persons, and sex‐ and age‐specific IRs) and examined the impact of two administrative changes. Our study included 9 107 157 people, followed for 233.0 million person‐years. During follow‐up, 9.5% were diagnosed with at least one mental disorder. The IR for any mental disorder was 39.0 per 10,000 person‐years. Despite fluctuations, this increased between 1970–84 and 2005–2016, from 28.9 to 63.0 per 10,000 person‐years. Increases were most pronounced for younger age groups. Administrative changes did appear to influence incidence rates. Mental disorder IRs have increased in Denmark since 1970, with age of diagnosis shifting downwards. Both trends were likely impacted by administrative changes, while the latter is likely to be (partly) attributable to earlier detection and increased reporting of child‐onset conditions. Our findings may provide valuable context of the epidemiology of mental disorders across age groups for comparison with other studies and populations.
Publisher: Public Library of Science (PLoS)
Date: 26-04-2012
Publisher: Wiley
Date: 04-2002
DOI: 10.1097/00005537-200204000-00002
Abstract: This is an overview of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheathing glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue s les were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic "lesion" of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added 1 month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called "neurogenesis"). Biopsy of this area and lification of cells in culture gives the scientist a "window to the developing brain," including early diagnosis of schizophrenia. The "Holy Grail" of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.BBR.2012.02.007
Abstract: Evidence from epidemiology suggests that developmental vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in rats is associated with altered brain morphology and enhanced hyperlocomotion in response to MK-801 and hetamine. The aim of this study was to determine if similar phenotypes were associated with DVD deficiency in two strains of mice (C57BL/6J, 129/X1SvJ). Brains from neonatal (P0) and adult (P70) mice were imaged using MRI and the volumes of the cerebrum, hippoc us, striatum, septum, cortex and ventricles measured, as well as the widths of white matter tracts. Locomotor sensitivity to 5mg/kg d- hetamine, 0.5mg/kg MK-801 or saline was examined in a separate group of mice in an open field. DVD deficiency altered brain morphology in C57BL6/J mice, such that C57BL/6J female DVD-deficient neonatal mice had a smaller hippoc us compared to female controls. In addition, adult C57BL/6J male DVD-deficient mice had smaller lateral ventricles compared to controls, which may have been compressed by the enlarged striatum seen in these DVD-deficient mice. However, in contrast to the behavioural phenotypes found in DVD-deficient rats, there was no significant effect of maternal diet on hetamine or MK-801-induced locomotion in either strain. These data indicate that not only species, but also strain of mouse, moderates the impact of DVD deficiency on neuroanatomical and behavioural phenotypes in rodent animal models.
Publisher: Cold Spring Harbor Laboratory
Date: 14-06-2022
DOI: 10.1101/2022.06.08.22276164
Abstract: The vitamin D binding protein (DBP), encoded by the group-specific component ( GC ) gene, is a much-studied component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates, we identified 26 independent loci, 17 of which were in or close to the GC gene, with fine-mapping identifying 2 loci on chromosomes 12 and 17 (missense variants within SH2B3 and GSDMA, respectively). When adjusted for key GC haplotypes, we found 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses found evidence consistent with a unidirectional, causal effect of higher DBP concentration and (a) higher 25 hydroxyvitamin D (25OHD) concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study in an external dataset confirmed that higher DBP concentration was associated with higher 25OHD concentration and a reduced risk of vitamin D deficiency. Our study provides new insights into the influence of DBP on vitamin D status and a range of health outcomes.
Publisher: Springer Science and Business Media LLC
Date: 07-2014
Publisher: Cold Spring Harbor Laboratory
Date: 27-11-2020
DOI: 10.1101/2020.11.27.401141
Abstract: The accuracy of polygenic risk scores (PRSs) to predict complex diseases increases with the training s le size. PRSs are generally derived based on summary statistics from large meta-analyses of multiple genome-wide association studies (GWAS). However, it is now common for researchers to have access to large in idual-level data as well, such as the UK biobank data. To the best of our knowledge, it has not yet been explored how to best combine both types of data (summary statistics and in idual-level data) to optimize polygenic prediction. The most widely used approach to combine data is the meta-analysis of GWAS summary statistics (Meta-GWAS), but we show that it does not always provide the most accurate PRS. Through simulations and using twelve real case-control and quantitative traits from both iPSYCH and UK Biobank along with external GWAS summary statistics, we compare Meta-GWAS with two alternative data-combining approaches, stacked clumping and thresholding (SCT) and Meta-PRS. We find that, when large in idual-level data is available, the linear combination of PRSs (Meta-PRS) is both a simple alternative to Meta-GWAS and often more accurate.
Publisher: BMJ
Date: 2012
Publisher: American Medical Association (AMA)
Date: 03-2019
Publisher: Springer Science and Business Media LLC
Date: 15-10-2007
Publisher: Elsevier BV
Date: 09-2014
Publisher: Elsevier BV
Date: 2000
Publisher: Springer Science and Business Media LLC
Date: 15-02-2023
DOI: 10.1038/S41467-023-36392-5
Abstract: The vitamin D binding protein (DBP), encoded by the group-specific component ( GC ) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA , respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.
Publisher: SAGE Publications
Date: 06-06-2023
DOI: 10.1177/14034948231178076
Abstract: We provide an overview of nationwide environmental data available for Denmark and its linkage potentials to in idual-level records with the aim of promoting research on the potential impact of the local surrounding environment on human health. Researchers in Denmark have unique opportunities for conducting large population-based studies treating the entire Danish population as one big, open and dynamic cohort based on nationally complete population and health registries. So far, most research in this area has utilised in idual- and family-level information to study the clustering of disease in families, comorbidities, risk of, and prognosis after, disease onset, and social gradients in disease risk. Linking environmental data in time and space to in iduals enables novel possibilities for studying the health effects of the social, built and physical environment. We describe the possible linkage between in iduals and their local surrounding environment to establish the exposome – that is, the total environmental exposure of an in idual over their life course. The currently available nationwide longitudinal environmental data in Denmark constitutes a valuable and globally rare asset that can help explore the impact of the exposome on human health.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Elsevier BV
Date: 08-2023
Publisher: American Medical Association (AMA)
Date: 10-11-2020
Publisher: Elsevier BV
Date: 08-2015
Publisher: SAGE Publications
Date: 09-12-2019
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.BBR.2012.12.029
Abstract: Evidence from epidemiological studies suggest that low levels of vitamin D during early life alter brain development and may increase the risk of various adverse health outcomes, including schizophrenia. The aim of this experiment was to examine the effect of developmental vitamin D (DVD) deficiency on attentional processing using the 5-choice serial reaction time task (5C-SRT) and the 5-choice continuous performance test (5C-CPT), which specifically assesses sustained attention and vigilance in rodents. DVD-deficient and control rats were exposed to a series of target and non-target trials within each operant testing session. A number of measures were recorded including hit, miss, false alarm and correct rejection, as well as premature and perseverative responses. Performance on 5C-CPT was also assessed after administration of the atypical antipsychotic, clozapine. The adult offspring of DVD-deficient rats had higher levels of impulsivity, as demonstrated by a significant increase in premature responses. On the 5C-SRT and target trials of the 5C-CPT, accuracy was not significantly affected by prenatal diet however DVD-deficient rats made 50% fewer correct rejections compared to controls on non-target trials of the 5C-CPT. Thus, control rats were able to discriminate between target and non-target trials, whereas DVD-deficient rats were unable to make this discrimination. Clozapine reduced the occurrence of false alarms in DVD-deficient rats to a level comparable to control values. Taken together these data suggest DVD-deficient rats have increased impulsivity as well as a lack of inhibitory control, and these features may be informative in terms of modeling the cognitive deficits observed in schizophrenia.
Publisher: American Psychiatric Association Publishing
Date: 08-2016
Publisher: Wiley
Date: 23-01-2006
DOI: 10.1111/J.1600-0447.2005.00742.X
Abstract: The aim of this study was to examine the association between latitude and the incidence and prevalence of schizophrenia based on two recently published systematic reviews. The analyses were based on 353 incidence rates (from 68 studies) and 258 prevalence estimates (from 94 studies). Exact latitude values were used for cities, and geocentroid values for other sites. Based on three equal latitude bands, we compared the frequency measures of schizophrenia for persons, males and females when adjusted for within-study variation. Prevalence estimates from sites in the high-latitude band were significantly higher when compared with lower bands for persons, males and females. Incidence rates were positively associated with absolute latitude for males, but neither for females nor persons. Variables that have latitude gradients warrant closer inspection in schizophrenia epidemiology.
Publisher: American Medical Association (AMA)
Date: 09-2018
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 2000
Publisher: American Medical Association (AMA)
Date: 02-2018
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.SCHRES.2007.11.024
Abstract: Delayed neuromotor development carries an increased risk of developing schizophrenia, and some authors have assumed that risk factors for schizophrenia such as delayed development are also prognostic indicators for patients with established illness. In those who do develop schizophrenia, it is not clear if these same early developmental markers influence the outcome of illness. Our aim was to examine the association between infant developmental milestones and a range of outcomes in patients with schizophrenia. Our s le was drawn from Northern Finland 1966 Birth Cohort and included 109 subjects for whom prospectively collected information on age of learning to stand, walk and talk was available and who had developed schizophrenia by the age 35 years. By utilizing national registers we examined outcomes related to service utilization, educational achievement, and occupational status. Age of illness onset was also analyzed. Based on the diagnostic interview, a subgroup of 59 cases was assessed in clinical examinations on functioning and quality of life. Contrary to a widespread assumption within the field of schizophrenia research, later attainment of developmental milestones was not associated with poor outcome. We conclude that risk factors for schizophrenia are not necessarily prognostic factors.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.PSYCHRES.2019.01.079
Abstract: Few studies have compared the content and appraisal of hallucinatory experiences (HE) by people with psychosis and those without. This study compared the characteristics of HE, and their appraisals, in in iduals with psychotic disorder, non-psychotic mental disorder and no disorder in the general population. Participants (n = 253) aged between 30-33 years who reported HE were recruited from a birth cohort and assessed for lifetime diagnoses of mental disorders. They were allocated to groups based on their diagnosis and their HE were rated to assess their form, content and associated appraisals. Compared to those with no mental disorder, participants with a psychotic disorder had almost twelve times the odds of appraising their HE as distressing and dangerous and nine times the odds of experiencing recurrent HE. Those with a non-psychotic disorder had more than twice the odds of recurrent HE compared to those with no disorder. Overall, HE showed more similarities than differences across the diagnostic groups. Negative appraisals of HE and their recurrence differentiated clinical from non-clinical populations. Screening for HE and assessment of their associated appraisals is essential in those seeking care for mental health difficulties. Interventions aimed at modifying maladaptive appraisals can assist in reducing hallucination related distress.
Publisher: Cambridge University Press (CUP)
Date: 02-01-2014
DOI: 10.1017/S0033291713002973
Abstract: There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities. The 2010 Australian national psychosis survey used a two-phase design to draw a representative s le of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants. The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s .d. s below the population mean current cognitive ability (measured with a digit symbol coding task) was 1.6 s .d .s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence. Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.
Publisher: Elsevier BV
Date: 05-2003
DOI: 10.1016/S0306-4522(03)00040-X
Abstract: Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain.
Publisher: Public Library of Science (PLoS)
Date: 21-08-2013
Publisher: Wiley
Date: 28-01-2016
DOI: 10.1111/CEA.12645
Abstract: Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma. We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children. We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood s les in mid-gestation and umbilical cord blood s les at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6. Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)]. Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2014
DOI: 10.1038/TP.2014.60
Publisher: Cambridge University Press (CUP)
Date: 30-01-2019
DOI: 10.1017/S0007114518003604
Abstract: Environmental factors such as sunshine hours, temperature and UV radiation (UVR) are known to influence seasonal fluctuations in vitamin D concentrations. However, currently there is poor understanding regarding the environmental factors or in idual characteristics that best predict neonatal 25-hydroxyvitamin D (25(OH)D) concentrations. The aims of this study were to (1) identify environmental and in idual determinants of 25(OH)D concentrations in newborns and (2) investigate whether environmental factors and in idual characteristics could be used as proxy measures for neonatal 25(OH)D concentrations. 25-Hydroxyvitamin D 3 (25(OH)D 3 ) was measured from neonatal dried blood spots (DBS) of 1182 in iduals born between 1993 and 2002. Monthly aggregated data on daily number of sunshine hours, temperature and UVR, available from 1993, were retrieved from the Danish Meteorological Institute. The in idual predictors were obtained from the Danish National Birth register, and Statistics Denmark. The optimal model to predict 25(OH)D 3 concentrations from neonatal DBS was the one including the following variables: UVR, temperature, maternal education, maternal smoking during pregnancy, gestational age at birth and parity. This model explained 30 % of the variation of 25(OH)D 3 in the neonatal DBS. Ambient UVR in the month before the birth month was the best single-item predictor of neonatal 25(OH)D 3 , accounting for 24 % of its variance. Although this prediction model cannot substitute for actual blood measurements, it might prove useful in cohort studies ranking in iduals in groups according to 25(OH)D 3 status.
Publisher: Elsevier BV
Date: 10-2001
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.NEUROIMAGE.2020.116514
Abstract: Low vitamin D level during pregnancy has been associated with adverse neurodevelopmental outcomes such as autism spectrum disorders (ASD) in children. However, the underlying neurobiological mechanism remains largely unknown. This study investigated the association between gestational 25-hydroxyvitamin D [25(OH)D] concentration and brain morphology in 2597 children at the age of 10 years in the population-based Generation R Study. We studied both 25(OH)D in maternal venous blood in mid-gestation and in umbilical cord blood at delivery, in relation to brain volumetric measures and surface-based cortical metrics including cortical thickness, surface area, and gyrification using linear regression. We found exposure to higher maternal 25(OH)D concentrations in mid-gestation was associated with a larger cerebellar volume in children (b = 0.02, 95%CI 0.001 to 0.04), however this association did not remain after correction for multiple comparisons. In addition, children exposed to persistently deficient (i.e., <25 nmol/L) 25(OH)D concentration from mid-gestation to delivery showed less cerebral gray matter and white matter volumes, as well as smaller surface area and less gyrification at 10 years than those with persistently sufficient (i.e., ≥50 nmol/L) 25(OH)D concentration. These results suggest temporal relationships between gestational vitamin D concentration and brain morphological development in children.
Publisher: American Medical Association (AMA)
Date: 05-2022
Publisher: Springer Science and Business Media LLC
Date: 26-05-2016
DOI: 10.1038/SREP26688
Abstract: Evidence has indicated that the incidence of colorectal cancer (CRC) among schizophrenia is lower than normal. To explore this potential protective effect, we employed an innovative strategy combining association study with allele-specific expression (ASE) analysis in MCC gene. We first genotyped four polymorphisms within MCC in 312 CRC patients, 270 schizophrenia patients and 270 controls. Using the MassArray technique, we performed ASE measurements in a second s le series consisting of 50 sporadic CRC patients, 50 schizophrenia patients and 52 controls. Rs2227947 showed significant differences between schizophrenia cases and controls, and haplotype analysis reported some significant discrepancies among these three subject groups. ASE values of rs2227948 and rs2227947 presented consistently differences between CRC (or schizophrenia) patients and controls. Of the three groups, highest frequencies of ASE in MCC were concordantly found in CRC group, whereas lowest frequencies of ASE were observed in schizophrenia group. Similar trends were confirmed in both haplotype frequencies and ASE frequencies (i.e. CRC control schizophrenia). We provide a first indication that MCC might confer alterative genetic susceptibility to CRC in in iduals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression.
Publisher: Wiley
Date: 15-09-2023
DOI: 10.1002/WPS.21110
Publisher: SAGE Publications
Date: 2004
DOI: 10.1111/J.1440-1614.2004.01301.X
Abstract: Deficits in olfactory identification have been demonstrated in patients with schizophrenia. This study examined the interaction between smoking and olfactory identification in patients with psychotic disorders versus well controls. Olfactory identification was assessed in three groups of subjects using the University of Pennsylvania Smell Identification Test (UPSIT). Sixteen patients with affective psychoses, 22 patients with nonaffective psychoses, and 21 well controls were tested. There was a significant interaction between diagnostic classification (patient or control) and smoking. Patients who were smokers scored higher on the UPSIT than non-smokers, while controls who were smokers scored lower than non-smokers. Smoking may have a 'normalising' effect on olfactory identification in some patients with psychosis. Further studies are needed to examine the relationship between psychosis, olfactory identification and the effects of nicotine.
Publisher: Springer Science and Business Media LLC
Date: 25-05-2022
DOI: 10.1038/S44184-022-00001-Y
Abstract: The aim of the study was to undertake a detailed analysis of healthcare cost, public transfer payments, and income loss associated with a broad range of mental disorders in Denmark. Based on all persons living in Denmark, we identified those with a hospital diagnosis of one of 18 types of mental disorders and 10 age- and sex-matched controls per case. For each mental disorder, the outcomes were nationwide totals, cost per case, and cost per capita, investigated by sex, age strata, and the number of years after diagnosis. We found a substantial annual income loss of 5 billion Euros and excess healthcare cost of 1 billion Euros for persons with any mental disorder. Each mental disorder was associated with an income loss, excess healthcare cost, and excess public transfer payments compared to matched controls. An interactive data visualisation site with summary data is available at ost .
Publisher: Wiley
Date: 10-12-2020
DOI: 10.1111/NYAS.14535
Publisher: SAGE Publications
Date: 20-06-2012
Abstract: Participation in mainstream education and employment facilitates both the recovery and the social inclusion of people with psychotic disorders. As part of the second Australian survey of psychosis, we assessed labour force activity and participation in formal education among working age adults with psychotic disorders. Data were drawn from a large national community prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas during March to December 2010. Current and past year labour force activity, current employment, past year participation in formal education and vocational training, and key clinical and demographic characteristics were examined in a s le of 1825 participants. Only 22.4% of people with psychotic disorders were found to be employed (either full-time or part-time) in the month prior to the survey. In the previous 12 months, 32.7% were employed at some time. Of those in competitive employment, the majority worked part-time (63.9%), while a quarter worked 38 or more hours per week (23.4%). In terms of educational attainment, 18.4% reported difficulties with reading or writing, while 31.9% completed high school, which represents 12 years of formal education. The proportion currently employed has remained stable at 22% since the last national survey in 1997. Policy makers and service providers could do more to ensure people with psychotic disorders obtain access to more effective forms of assistance with respect to both their continuing education and employment. More effective vocational and educational interventions for people with psychotic disorders appear to be urgently needed.
Publisher: Elsevier BV
Date: 08-1996
DOI: 10.1016/S0952-3278(96)90153-2
Abstract: The neurodevelopmental hypothesis of schizophrenia implicates abnormal or disrupted neural growth during embryogenesis. It is postulated here that stress-inducing agents acting upon a compromised cellular system resulting from abnormal plasma membrane lipids could effect the neuronal abnormalities observed in schizophrenia. The heat stress response is induced by exposure to hyperthermia as well as a variety of other agents. The response to these agents includes the cessation of most transcriptional and translational activities, accompanied by the induction of a highly specific set of proteins. A concomitant reduction in metabolic activity including cell cycle delays is also observed. Much of the enormous literature on the heat stress response concentrates on protein and DNA interactions, especially with regard to transcriptional control. However, a variety of lipids are intrinsically involved in the heat stress response. This paper will provide a brief introduction to the heat shock proteins and will explore the roles that lipids play in the heat shock response.
Publisher: SAGE Publications
Date: 13-05-2021
DOI: 10.1177/00048674211009615
Abstract: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that in iduals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.
Publisher: American Medical Association (AMA)
Date: 07-2015
Publisher: Elsevier BV
Date: 2015
Publisher: Wiley
Date: 03-2007
Abstract: An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. To explore a possible link between maternal vitamin D deficiency and these brain disorders, we examined the impact of prenatal hypovitaminosis D on protein expression in the adult rat brain. Vitamin D-deficient female rats were mated with vitamin D normal males. Pregnant females were kept vitamin D-deficient until birth whereupon they were returned to a control diet. At week 10, protein expression in the progeny's prefrontal cortex and hippoc us was compared with control animals using silver staining 2-D gels associated with MS and newly devised data mining software. Developmental vitamin D (DVD) deficiency caused a dysregulation of 36 brain proteins involved in several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, PTMs, synaptic plasticity and neurotransmission. A computational analysis of these data revealed that (i) nearly half of the molecules dysregulated in our animal model have also been shown to be misexpressed in either schizophrenia and/or multiple sclerosis and (ii) an impaired synaptic network may be a consequence of mitochondrial dysfunction.
Publisher: Oxford University Press (OUP)
Date: 30-03-2009
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.SCHRES.2014.07.011
Abstract: Child abuse has been associated with risk of mental illness, including schizophrenia and other psychotic disorders and, among those with mental illness, with a more severe clinical profile. Using an extensively characterised and epidemiologically representative s le of 1825 Australians with a psychotic illness aged 18-64 years and in contact with mental health services, we estimated the proportion of in iduals with psychotic disorders who self-reported child abuse and examined its relationship with clinical and other characteristics. The prevalence of child abuse in this nationally representative s le of people with psychotic illness was 30.6%. Women were almost three times more likely to report child abuse compared to males (OR, 2.8, 95% CI 2.3-3.4). When adjusted for age at interview and socio-economic status, there was no significant relationship between self-reported child abuse and type of psychosis or course of illness. Participants with child abuse were significantly more likely to have subjective thought disorder, lifetime suicide attempt and premorbid personality disorder (females only) and anxiety (males only). Our findings demonstrate that child abuse is relatively common across the range of psychotic disorders, with an elevated risk for women in particular, compounding the already high burden associated with psychotic illness. Clinicians need to inquire routinely about child abuse in order to develop appropriate treatment plans tailored to in idual needs.
Publisher: Public Library of Science (PLoS)
Date: 25-07-2012
Publisher: Elsevier BV
Date: 03-2013
Publisher: Elsevier BV
Date: 12-1994
DOI: 10.1016/0920-9964(94)90002-7
Abstract: The dates of birth of patients who were admitted with schizophrenia to public hospitals in Queensland between the years 1972 and 1988 were examined for associations between risk of schizophrenia and influenza epidemics. The hypothesis that infants born between four and six months after an influenza epidemic onset have increased risk of schizophrenia was examined for the 1954, 1957 and 1959 epidemics. After the 1954 epidemic there was a significant excess of male schizophrenia births four months after the onset of the epidemic. In 1957, there was a significant excess of female schizophrenia births in the fifth month after the onset of the epidemic. The 1959 epidemic was not associated with any significant excess.
Publisher: American Medical Association (AMA)
Date: 03-06-2020
Publisher: Elsevier BV
Date: 04-2017
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.BRAINRESBULL.2005.10.014
Abstract: Animal experiments have shown that Vitamin D plays a role in both brain development and adult brain function. The adult Vitamin D receptor null mutant mouse (VDR -/-) is reported to be less active and more anxious than wild-type litter mate controls and to have poor swimming ability. However, an "anxious" behavioural phenotype is inferred from differences in locomotor behaviour. This is a general problem in behavioural phenotyping where a neurological phenotype is inferred from changes in locomotion which will be affected by non-neurological factors, such as muscle fatigue. In this study of VDR -/-, we conducted a detailed examination of one form of motor behaviour, swimming, compared to wildtype littermate controls. Swimming was assessed using a forced swim test, a laneway swimming test and a watermaze test using a visible platform. Post-swimming activity was assessed by comparing grooming and rearing behaviour before, and 5 min after, the forced swimming test. We replicated previous findings in which VDR -/- mice demonstrate more sinking episodes than wildtype controls in the forced swim test but they were similar to controls in the time taken to swim a 1m laneway, and in the time taken to reach a visible platform in the watermaze. Thus, the VDR -/- mice were able to swim but were not able to float. Grooming and rearing behaviour of the VDR -/- mice was similar to wildtype controls before the forced swim but the VDR -/- were much less active after the swim compared with wildtype mice which displayed high levels of grooming and rearing. We conclude that VDR -/- mice have muscular and motor impairments that do not affect their ability to swim but significantly alters the ability to float as well as their post-swimming activity. Differences in muscle strength may confound tests of activity that are used to infer an "anxious" phenotype.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2018
Publisher: Elsevier BV
Date: 05-2004
Publisher: Cambridge University Press (CUP)
Date: 29-06-2017
DOI: 10.1017/S0033291717001696
Abstract: Studies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case–control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia. Data were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis. Those with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01–1.40], but not at birth (OR 1.09, 95% CI 0.95–1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18–2.02 overall p = 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97–1.78 overall p = 0.148). While results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JSBMB.2014.11.004
Abstract: Over the last decade a convergent body of evidence has emerged from epidemiology, animal experiments and clinical trials which links low vitamin D status with a range of adverse neuropsychiatric outcomes. This research demonstrates that the timing of exposure to low vitamin D influences the nature of brain phenotypes, as exposures during gestation versus adulthood result in different phenotypes. With respect to early life exposures, there is robust evidence from rodent experiments indicating that transient developmental vitamin D (DVD) deficiency is associated with changes in brain structure, neurochemistry, gene and protein expression and behavior. In particular, DVD deficiency is associated with alterations in the dopaminergic neurotransmitter systems. In contrast, recently published animal experiments indicate that adult vitamin D (AVD) deficiency is associated with more subtle neurochemical and behavioral phenotypes. This paper explores key issues that need to be addressed in future research. There is a need to define the timing and duration of the 'critical window' during which low vitamin D status is associated with differential and adverse brain outcomes. We discuss the role for 'two-hit hypotheses', which propose that adult vitamin D deficiency leaves the brain more vulnerable to secondary adverse exposures, and thus may exacerbate disease progression. Finally, we explore the evidence implicating a role for vitamin D in rapid, non-genomic mechanisms that may involve L-type calcium channels and brain function. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.SCHRES.2018.11.003
Abstract: People with schizophrenia have an increased risk of premature mortality compared to the general population. We aimed to quantify which types of causes of death contributed to the excess mortality, and to examine whether there has been an increase in the excess mortality among persons with schizophrenia in the period 1995 to 2015. We used a cohort design including the entire Danish population. We calculated life years lost of the cohort members compared to a set reference-age at 95 years old. Using a decomposition model we examined differences of cause-specific death among those with schizophrenia and the general population, including calendar trends during the last two decades. In the general population, as well as in persons with schizophrenia, we found improvements in life years lost during the last two decades. Men with schizophrenia lost 13.5 years more than the general population (women 11.4 years). Compared to the general population, a large improvement in life years lost with respect to suicide and accidents was found in those with schizophrenia, but, this improvement was offset by an increasing number of life years lost in deaths from diseases and medical conditions. Our findings highlight the urgent need for focused treatment of general medical conditions in those with schizophrenia. Without such an investment, it is probable that the life years lost among persons with schizophrenia (compared to the general population) will continue to worsen in future decades.
Publisher: Elsevier BV
Date: 2000
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.PSYNEUEN.2017.09.003
Abstract: Vitamin D deficiency is prevalent in adults throughout the world. Epidemiological studies have shown significant associations between vitamin D deficiency and an increased risk of various neuropsychiatric and neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease and cognitive impairment. However, studies based on observational epidemiology cannot address questions of causality they cannot determine if vitamin D deficiency is a causal factor leading to the adverse health outcome. The main aim of this study was to determine if AVD deficiency would exacerbate the effects of a secondary exposure, in this case social stress, in BALB/c mice and in the more resilient C57BL/6 mice. Ten-week old male BALB/c and C57BL/6 mice were fed a control or vitamin D deficient diet for 10 weeks, and the mice were further separated into one of two groups for social treatment, either Separated (SEP) or Social Defeat (DEF). SEP mice were placed two per cage with a perforated Plexiglas ider, whereas the DEF mice underwent 10days of social defeat prior to behavioural testing. We found that AVD-deficient mice were more vulnerable to the effects of social stress using a social avoidance test, and this was dependent on strain. These results support the hypothesis that vitamin D deficiency may exacerbate behavioural outcomes in mice vulnerable to stress, a finding that can help guide future studies. Importantly, these discoveries support the epidemiological link between vitamin D deficiency and neuropsychiatric and neurodegenerative disorders and has provided clues that can guide future studies related to unravelling the mechanisms of action linking adult vitamin D deficiency and adverse brain related outcomes.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2018
DOI: 10.1038/S41598-018-35418-Z
Abstract: Clues from the epidemiology of schizophrenia, such as the increased risk in those born in winter/spring, have led to the hypothesis that prenatal vitamin D deficiency may increase the risk of later schizophrenia. We wish to explore this hypothesis in a large Danish case-control study (n = 2602). The concentration of 25 hydroxyvitamin D (25OHD) was assessed from neonatal dried blood s les. Incidence rate ratios (IRR) were calculated when examined for quintiles of 25OHD concentration. In addition, we examined statistical models that combined 25OHD concentration and the schizophrenia polygenic risk score (PRS) in a s le that combined the new s le with a previous study (total n = 3464 s les assayed and genotyped between 2008-2013). Compared to the reference (fourth) quintile, those in the lowest quintile ( .4 nmol/L) had a significantly increased risk of schizophrenia (IRR = 1.44, 95%CI: 1.12–1.85). None of the other quintile comparisons were significantly different. There was no significant interaction between 25OHD and the PRS. Neonatal vitamin D deficiency was associated with an increased risk for schizophrenia in later life. These findings could have important public health implications related to the primary prevention of schizophrenia.
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.BBR.2006.07.015
Abstract: Transient prenatal vitamin D deficiency produces hyperlocomotion in the adult rat. The aim of this study was to examine the effects of acute restraint on the behaviour of DVD and control rats in the open field. Rats were conceived and born to developmentally vitamin D (DVD) deficient or replete (control) dams and, at 8 weeks of age, were monitored for 30 min in an open field using automated video tracking software. Half of the rats were restrained within a towel for 5 min immediately before the open field test. The remainder received minimal handling prior to the open field test. Repeating previous findings, DVD deficient animals had enhanced locomotion during the first 10 min of the open field test compared to control rats. By contrast, there were no differences in locomotor activity after acute restraint stress. The time rats spent in the corners and side of the open field was affected by prenatal diet. DVD rats spent less time in the corners and more time in the side than control rats across the whole 30 min test. This difference was not seen in rats with acute restraint stress. The time spent in the centre was not altered by prenatal diet or acute restraint. Thus, transient prenatal vitamin D deficiency induces a transient spontaneous hyperlocomotion in adulthood that is modulated by acute restraint stress.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0920-9964(02)00435-8
Abstract: Evidence from epidemiology suggests that low maternal vitamin D may be a risk factor for schizophrenia. Based on sera taken during the third trimester, we compared the level of 25 hydroxyvitamin D3 in mothers of in iduals with schizophrenia or schizoaffective disorders versus mothers of unaffected controls. For each case, we selected two controls matched on race, gender and date of birth of the offspring. There was no significant difference in third trimester maternal vitamin D in the entire s le (cases = 26, controls = 51). Within the subgroup of black in iduals (n = 21), there was a trend level difference in the predicted direction. Maternal vitamin D does not operate as a continuous graded risk factor for schizophrenia, however, the results in the black subgroup raise the possibility that below a certain critical threshold, low levels of maternal vitamin D may be associated with an increased risk of schizophrenia.
Publisher: Informa UK Limited
Date: 2003
DOI: 10.1080/07853890310010005
Abstract: The neurodevelopmental hypothesis (NDH) of schizophrenia suggests that a disruption of brain development during early life underlies the later emergence of psychosis during adulthood. The aim of this review is to chart the challenges and subsequent refinements to this hypothesis, with particular reference to the static versus progressive nature of the putative neurobiological processes underlying the NDH. A non-systematic literature review was undertaken, with an emphasis on major review papers relevant to the NDH. Weaknesses in the explanatory power of the NDH have led to a new generation of more refined hypotheses in recent years. In particular, recent versions of the hypothesis have incorporated evidence from structural neuroimaging which suggests changes in brain volumes after the onset of schizophrenia. More detailed models that incorporate progressive neurobiological processes have replaced early versions of the NDH, which were based on a 'static encephalopathy'. In addition, recent models have suggested that two or more 'hits' are required over the lifespan rather than only one early-life event. Animal models are providing important insights into the sequelae of disturbed early brain development. The NDH has provided great impetus to the schizophrenia research community. Recent versions of the hypothesis have encouraged more focused and testable hypotheses.
Publisher: Cold Spring Harbor Laboratory
Date: 28-06-2023
DOI: 10.1101/2023.06.23.23291796
Abstract: In previous studies, null results from sibling comparison designs have been used to infer that no causal association exists between childhood family income and subsequent risk of mental disorders. The aim of our study is to replicate the findings from previous studies and propose three alternative explanations based on i) variability in income and mental health between siblings, ii) life course models, and iii) detailed descriptive statistics. We followed a nationwide Danish cohort born from 1986 to 1996 (n = 643,814, including 404,179 siblings) from age 15 until diagnosis of severe mental disorders or censoring. Adjusted hazard ratios (aHR) were estimated between childhood family income and subsequent mental disorders, accompanied by comprehensive descriptive statistics and triangulation analyses that help in interpreting the findings. We observed an association between a $15,000 increase in family income and severe mental disorders (0.78 0.76-0.81), but the sibling comparison design showed null results (1.02 0.94-1.11). Siblings were typically born three years apart, with a difference in monthly average income at age 14 of $496 (interquartile range: $150-$641). A pseudo-sibling cohort also indicated null results (0.93 0.85-1.01), although siblings were not family members. Family income measured yearly demonstrated comparable estimates across ages 1-14 (from 0.67 to 0.82). Our investigation suggests that the null associations between childhood income and mental health estimated through sibling comparison designs may be explained by the fact that siblings are close together in age and residing within the same family income environment with only minor income fluctuations. Additionally, a sibling comparison design is useful to test a critical/sensitive period, but our analyses suggest that no age posits a critical risk age for this research question. This raises caution on the current practice of relying on sibling comparison designs to estimate the association between childhood income and mental health.
Publisher: Cambridge University Press (CUP)
Date: 23-10-2015
Publisher: Cambridge University Press
Date: 2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: Cambridge University Press (CUP)
Date: 27-08-2014
DOI: 10.1017/S2045796014000535
Abstract: The links between migrant status and psychosis have attracted considerable attention in recent decades. The aim of the study was to explore the demographic and clinical correlates of migrant v . Australia-born status in in iduals with psychotic disorders using a large community-based s le. Data were drawn from a population-based prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas in 2010. Logistic regression was used for the main analyses, examining associations of migrant status with sociodemographic and clinical variables. Of the 1825 participants with psychotic disorders, 17.8% ( n = 325) were migrants, of whom 55.7% ( n = 181) were male. Compared to Australia-born in iduals with psychosis, migrants were more likely to be currently married, to have completed a higher level at school, to have left school later, and to be employed with full-time jobs. Migrants with psychosis were either no different from or less impaired or disadvantaged compared to their Australian-born counterparts on a range of clinical and demographic variables. In a s le of in iduals with psychotic disorders, there was no evidence to suggest that migrant status was associated with worse clinical or socio-economic outcomes compared to their native-born counterparts.
Publisher: Elsevier BV
Date: 09-2002
DOI: 10.1016/S0920-9964(01)00299-7
Abstract: Calcium-binding proteins (CBPs) such as calbindin, parvalbumin and calretinin are used as immunohistochemical markers for discrete neuronal subpopulations. They are particularly useful in identifying the various subpopulations of GABAergic interneurons that control output from prefrontal and cingulate cortices as well as from the hippoc us. The strategic role these interneurons play in regulating output from these three crucial brain regions has made them a focus for neuropathological investigation in schizophrenia. The number of pathological reports detailing subtle changes in these CBP-containing interneurons in patients with schizophrenia is rapidly growing. These proteins however are more than convenient neuronal markers. They confer survival advantages to neurons and can increase the neuron's ability to sustain firing. These properties may be important in the subtle pathophysiology of nondegenerative phenomena such as schizophrenia. The aim of this review is to introduce the reader to the functional properties of CBPs and to examine the emerging literature reporting alterations in these proteins in schizophrenia as well as draw some conclusions about the significance of these findings.
Publisher: Springer Science and Business Media LLC
Date: 17-04-2007
Abstract: To identify genes dysregulated in bipolar disorder (BD1), we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls, we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by >or=1.3-fold in three BD1 cases compared to their co-twins, and which were statistically (P<or=0.05) differentially expressed between the groups of BD1 cases and controls. Using quantitative reverse transcriptase-polymerase chain reaction, we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1 and PI4KCB, in at least two of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design, our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis, we identified upregulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1.
Publisher: MDPI AG
Date: 30-08-2012
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JPSYCHIRES.2017.06.013
Abstract: Previous studies provide mixed evidence that physical activity engagement (PAE) in adolescence is associated with later mental health outcomes. This study aimed to examine the association between PAE at age 14 and mental health outcomes at age 21 using a large birth cohort study. Prospective data from the Mater-University of Queensland Study of Pregnancy, consisting of 3493 young adults, were analyzed. PAE at age 14 was estimated using self-report, and participants were categorized into (1) frequent, (2) infrequent, or (3) no PAE group. Mental health outcomes at age 21 consisted of (1) common mental disorders, (2) psychosis-related outcomes, and, (3) emotional and behavioral problems. The association between PAE in adolescence and later mental health outcomes in young adulthood was examined using logistic regression, adjusted for age, sex, body mass index, and adolescent psychopathology. No PAE at age 14 was associated with the increased likelihood of lifetime diagnosis of any affective disorder, elevated delusional ideation, and endorsement of visual perceptual disturbance at age 21. Conversely, infrequent PAE at age 14 was associated with the decreased likelihood of subsequent lifetime diagnosis of any substance use disorder. Our findings suggest that lack of PAE in adolescence influences some, but not all, later mental health outcomes. Interventions to increase PAE in adolescence may represent an opportunity to prevent future mental health problems.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JPSYCHIRES.2018.12.003
Abstract: Low physical activity is a major public health concern. There has been extensive research examining the role of physical activity as a potentially modifiable risk factor for the onset of mental illness. However, fewer studies have reported how mental disorders affect future physical activity. Using data from a large birth cohort, the current study explored the association between the longitudinal course of common mental disorders (affective disorders, anxiety disorders, and substance use disorders, as well as any common mental disorder) and subsequent physical activity status among young adults living in Australia. Prospective data from the Mater-University of Queensland Study of Pregnancy, consisting of 1611 young adults, were analyzed. The longitudinal course of mental disorder diagnoses between ages 21 and 30 was derived from the Composite International Diagnostic Interview. Physical activity status at age 30 was estimated using International Physical Activity Questionnaire long form. Logistic regression was used to examine the association between the longitudinal course of common mental disorders between 21 and 30 years and subsequent physical activity status at age 30. After adjusting for confounding factors, there was no association between the longitudinal course of affective disorders, anxiety disorders, substance use disorders, or any common mental disorder at ages 21 and 30 and physical activity status at age 30. Our findings suggest that there is no longitudinal association between the common mental disorder diagnoses and physical activity status among young adults living in Australia.
Publisher: Longdom Group
Date: 2013
Publisher: Elsevier BV
Date: 05-03-2008
DOI: 10.1016/J.BBR.2007.09.032
Abstract: Developmental vitamin D (DVD) deficiency has been proposed as an environmental risk factor for a number of brain disorders. The absence of this vitamin during foetal development in the rat is known to alter behaviour in the adult, and many of these alterations are informative with respect to the clinical features of schizophrenia. Here we investigated whether DVD deficiency had a similar effect on 129/SvJ and C57BL/6J mice. Female mice were fed a diet deficient in vitamin D for 6 weeks prior to conception until birth, after which dams and their offspring were fed a normal diet (i.e. containing vitamin D). Control mice were fed a normal diet throughout the experiment. The adult offspring underwent a comprehensive behavioural test battery at 10 weeks of age. We found that DVD-deficient mice of both strains exhibited significantly higher levels of exploration, as measured by the frequency of head dipping on the hole board test. In addition, DVD-deficient 129/SvJ mice, but not C57BL/6J mice, displayed spontaneous hyperlocomotion. There was no effect of maternal diet on parameters assessed by the SHIRPA primary screen, or on tests of sensorimotor gating, social behaviour, anxiety or depression. Some of these findings resemble the rat phenotype (hyperlocomotion) but there are also novel effects of DVD deficiency on mouse behaviour (increased exploration). This study confirms that the developmental absence of this vitamin affects brain function in another species (mouse), and lends further weight to the hypothesis that DVD deficiency in humans may contribute to adverse neuropsychiatric outcomes.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2021
DOI: 10.1038/S41380-021-01025-0
Abstract: Many epidemiological studies have highlighted the link between vitamin D deficiency and schizophrenia. In particular, two prominent studies report an association between neonatal vitamin D deficiency and an increased risk of schizophrenia. In parallel, much has been learnt about the role of vitamin D in the developing central nervous system over the last two decades. Studies in rodent models of developmental vitamin D (DVD)-deficiency describe how brain development is altered leading to a range of neurobiological and behavioral phenotypes of interest to schizophrenia. While glutamate and gamma aminobutyric acid (GABA) systems have been little investigated in these models, alterations in developing dopamine systems are frequently reported. There have been far more studies reporting patients with schizophrenia have an increased risk of vitamin D deficiency compared to well controls. Here we have conducted a systematic review and meta-analysis that basically confirms this association and extends this to first-episode psychosis. However, patients with schizophrenia also have poorer general health, poorer diets, are frequently less active and also have an increased risk of other medical conditions, all factors which reduce circulating vitamin D levels. Therefore, we would urge caution in any causal interpretation of this association. We also summarize the inconsistent results from existing vitamin D supplementation trials in patients with schizophrenia. In respect to animal models of adult vitamin D deficiency, such exposures produce subtle neurochemical alterations and effects on cognition but do not appear to produce behavioral phenotypes of relevance to schizophrenia. We conclude, the hypothesis that vitamin D deficiency during early life may increase the risk of schizophrenia remains plausible and warrants ongoing research.
Publisher: Elsevier BV
Date: 11-2019
Publisher: Oxford University Press (OUP)
Date: 12-05-2018
Publisher: Oxford University Press (OUP)
Date: 30-03-2009
Publisher: Elsevier BV
Date: 05-2013
Publisher: Annual Reviews
Date: 17-07-2014
DOI: 10.1146/ANNUREV-NUTR-071813-105557
Abstract: Vitamin D deficiency is prevalent throughout the world, and growing evidence supports a requirement for optimal vitamin D levels for the healthy developing and adult brain. Vitamin D has important roles in proliferation and differentiation, calcium signaling within the brain, and neurotrophic and neuroprotective actions it may also alter neurotransmission and synaptic plasticity. Recent experimental studies highlight the impact that vitamin D deficiency has on brain function in health and disease. In addition, results from recent animal studies suggest that vitamin D deficiency during adulthood may exacerbate underlying brain disorders and/or worsen recovery from brain stressors. An increasing number of epidemiological studies indicate that vitamin D deficiency is associated with a wide range of neuropsychiatric disorders and neurodegenerative diseases. Vitamin D supplementation is readily available and affordable, and this review highlights the need for further research.
Publisher: Wiley
Date: 31-01-2023
DOI: 10.1111/ADD.16122
Abstract: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost‐effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD. A prediction model was developed for DSM‐IV AD onset by age 25 years using an ensemble machine‐learning algorithm known as ‘Super Learner’. Shapley additive explanations (SHAP) assessed variable importance. Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys. The primary outcome to be predicted was onset of life‐time DSM‐IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview. AD prevalence by age 25 was 5.1% among the 10 687 in iduals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78 95% confidence interval (CI) = 0.74–0.81] higher than any in idual candidate risk model (0.73–0.77) and an area under the precision‐recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%] however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders. A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models.
Publisher: Cambridge University Press (CUP)
Date: 15-02-2013
DOI: 10.1017/S0033291713000196
Abstract: Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a s le collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate in idual PSSs in our independent s le of 350 schizophrenia patients and 322 healthy controls. Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls ( p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status ( R 2 = 0.055, p = 2.1 × 10 −7 ) and with IQ in the entire s le ( R 2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status. Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk.
Publisher: Elsevier BV
Date: 10-2004
DOI: 10.1016/J.DEVBRAINRES.2004.07.013
Abstract: Recently, it has been shown that the prenatal vitamin D(3) depletion is associated with altered brain development. Given the antiproliferative and pro-apoptotic properties of vitamin D(3) in various cell types, we examined the effects of maternal vitamin D(3) deprivation on cell proliferation and apoptosis within the rat cortex at several developmental stages. Our results confirm that vitamin D(3) regulates these processes in the developing brain at both cellular and molecular levels. Compared to control animals, the embryos and pups from vitamin D(3) depleted mothers had significantly less apoptotic cells, this finding being most pronounced at birth. Additionally, there were significantly more mitotic cells but this was not associated with any particular developmental period. Targeted gene arrays specific for apoptosis and cell cycle genes confirmed a pattern of transcription deregulation in the deplete group consistent with the known properties of vitamin D(3). While most current vitamin D(3) research is focussed on the pro-apoptotic and prodifferentiating properties of vitamin D(3) as adjuncts for the treatment of cancers, our findings highlight the important role that this hormone plays in normal development via these same properties specifically in the brain.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.JCHEMNEU.2004.08.006
Abstract: Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning, there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D3 receptor (VDR), and 1alpha-hydroxylase (1alpha-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1alpha-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1alpha-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1alpha-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substantia nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1alpha-OHase and the VDR suggests that Vitamin D may have autocrine aracrine properties in the human brain.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Elsevier BV
Date: 2000
Publisher: Elsevier BV
Date: 03-2003
Publisher: Public Library of Science (PLoS)
Date: 27-09-2005
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.MOLMED.2014.11.005
Abstract: Converging evidence from epidemiological, genetic, and animal studies supports the hypothesis that advancing parental age, both of the father and mother, increases the risk of autism spectrum disorders (ASD) in offspring. Paternal age has received considerable attention, with whole-genome sequencing studies linking older fathers to higher rates of de novo mutations and increased risk of ASD. The current evidence suggests that the increased risk of ASD in the offspring of older mothers may be related to mechanisms different from those operating in older fathers. Causal pathways probably involve the interaction of multiple risk factors. Although the etiology of ASD is still poorly understood, studies of parental age provide clues into the genetic and environ-mental mechanisms that mediate the risk of ASD.
Publisher: Swansea University
Date: 19-10-2022
Abstract: IntroductionSurveys and registers have provided important insights into the mental health of the community. However, both sources have strengths and limitations. While participation in surveys has been shown to be lower among those with mental disorders, misclassification and limited information on confounders are typical issues for registers. ObjectivesTo examine if participants of the Central Denmark Region's 2017 How are you? survey were representative of the general population in terms of mental disorder diagnoses. MethodsBy linking data from the Central Denmark Region's 2017 How are you? survey with the Danish national registers, we compared the frequency of mental disorder diagnoses among (a) participants in the survey (n = 32,417), before and after applying non-response weights, and (b) the entire population who were eligible to participate (n = 1,063,082 16 years of age or older on 10th January 2017 and registered as living in the Central Denmark Region). Using logistic regression models, we estimated associations between being diagnosed with any mental disorder and nine general medical conditions to assess whether selection into the survey appeared to bias these associations. ResultsBased on register data, 10.4% (n = 110,492) of the eligible population had received a diagnosis of any mental disorder prior to the date of this survey. Among the unweighted survey s le, 8.2% (n = 2,648) had received a diagnosis once non-response weights were applied, this corresponded to 9.5%. Representativeness varied by sex, age and type of mental disorder. For ex le, people with organic disorders or substance use disorders were generally underrepresented among survey participants of all ages however, representativeness of common disorders such as mood or neurotic disorders was generally good. With respect to the association of any mental disorder and general medical conditions, we found that estimates were similar for survey s les (both weighted and unweighted) compared to the entire eligible population. ConclusionsPeople with a previous diagnosis of a mental disorder are slightly underrepresented in the survey. However, this selection bias was minimized when non-response weights were applied. Associations between mental disorders and general medical conditions did not appear to be affected by selection bias. With the application of non-response weights, the survey provided a s le representative of the general population in terms of mental disorder diagnoses.
Publisher: American Medical Association (AMA)
Date: 11-2017
Publisher: American Medical Association (AMA)
Date: 05-2013
Publisher: Cambridge University Press (CUP)
Date: 26-02-2018
DOI: 10.1017/S0033291718000363
Abstract: Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders. In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments. After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4). PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2022
Publisher: Royal College of Psychiatrists
Date: 23-07-2021
DOI: 10.1192/BJP.2021.104
Abstract: Comorbidity with general medical conditions is common in in iduals with eating disorders. Many previous studies do not evaluate types of eating disorder. To provide relative and absolute risks of bidirectional associations between (a) anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified and (b) 12 general medical conditions. We included all people born in Denmark between 1977 and 2010. We collected information on eating disorders and considered the risk of subsequent medical conditions, using Cox proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered risks for prior medical conditions and subsequent eating disorders. An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a medical condition ranged from 0.94 (95% CI 0.57−1.55) to 2.05 (95% CI 1.86−2.27). For those with a prior medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI 1.26–1.45) to 1.98 (95% CI 1.71–2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared with reference groups. This is the largest and most detailed examination of eating disorder–medical condition comorbidity. The findings indicate that medical condition comorbidity is increased among those with eating disorders and vice versa . Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2016
DOI: 10.1038/MP.2016.213
Publisher: Cambridge University Press (CUP)
Date: 25-01-2012
DOI: 10.1017/S2045796011000862
Abstract: Population-based studies have identified that delusional-like experiences (DLEs) are common in the general population. While there is a large literature exploring the relationship between poor social support and risk of mental illness, there is a lack of empirical data examining the association of poor social support and DLEs. The aim of the study was to explore the association between social support and DLEs using a large, nationally representative community s le. Subjects were drawn from a national multistage probability survey of 8841 adults aged between 16 and 85 years. The Composite International Diagnostic Interview was used to identify DLEs, common psychiatric disorders and physical disorders. Eight questions assessed various aspects of social support with spouse artners and other family and friends. We examined the relationship between DLEs and social support using logistic regression, adjusting for potential confounding factors. Of the s le, 8.4% ( n = 776) positively endorsed one or more DLEs. In iduals who (a) had the least contact with friends, or (b) could not rely on or confide in spouse artner, family or friends were significantly more likely to endorse DLEs. The associations remained significant after adjusting for a range of potential confounding factors. DLEs are associated with impoverished social support in the general population. While we cannot exclude the possibility that the presence of isolated DLEs results in a reduction of social support, we speculate that poor social support may contribute in a causal fashion to the risk of DLEs.
Publisher: Wiley
Date: 31-05-2018
DOI: 10.1111/ADD.14252
Publisher: Elsevier BV
Date: 05-2022
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.EARLHUMDEV.2005.03.013
Abstract: Birth weight is known to fluctuate with season of birth, however, there is little information about seasonal variation in neonatal anthropometric measures. The aim of this study was to examine seasonal fluctuations in birth weight and selected anthropometric measures. The birth weight of singletons born after at least 37 weeks gestation was extracted from a perinatal register in south-east Queensland (n=350,171). Mean monthly birth weights for this period were examined. Based on a separate birth cohort, principal component analysis was undertaken on neonatal anthropometric measures (n=1233). Seasonality was assessed by (a) spectral analysis of time series data, (b) monthly and seasonal comparison of outcomes. Based on register data, birth weight displayed clear annual periodicity. Birth weight differed significantly when compared by month and season. Infants born in October were the heaviest (3484 g), while May-born infants were the lightest (3459 g P=0.001). Based on the cohort anthropometric data, three components were identified related to (a) overall size, (b) limb length, and (c) head size and skin-fold thickness. Each of these components displayed significant seasonal variation. In particular, prominent seasonal fluctuations in limb length were identified, with peak limb length associated with winter/spring birth. Environmental factors that have regular seasonal fluctuation influence both the size and shape of neonates. Animal experiments suggest that prenatal hypovitaminosis D may underlie greater limb length. Because birth weight and limb length are associated with a broad range of important health outcomes, the seasonal exposures underlying these effects warrant further scrutiny from a public health perspective.
Publisher: Elsevier BV
Date: 12-1999
DOI: 10.1016/S0920-9964(99)00052-3
Abstract: The central nervous system is increasingly being recognised as a target organ for vitamin D via its wide-ranging steroid hormonal effects and via the induction of various proteins such as nerve growth factor. This paper proposes that low maternal vitamin D may impact adversely on the developing foetal brain, leaving the affected offspring at increased risk of adult-onset schizophrenia. The hypothesis can parsimoniously explain erse epidemiological features of schizophrenia, such as the excess of winter births, increased rates of schizophrenia in dark-skinned migrants to cold climates, the increased rate of schizophrenia births in urban versus rural setting, and the association between prenatal famine and schizophrenia. Studies that will allow rejection of the hypothesis are proposed.
Publisher: Public Library of Science (PLoS)
Date: 08-10-2013
Publisher: SAGE Publications
Date: 06-2002
DOI: 10.1046/J.1440-1614.2001.01006.X
Abstract: To examine the association between prenatal exposure to poliovirus infection and later development of schizophrenia or affective psychosis in a Southern Hemisphere psychiatric register. We calculated rates of poliomyelitis cases per 10 000 background population and rates for schizophrenia(n = 6078) and affective psychosis (n = 3707)per 10 000 births for the period 1930-1964. Empirically weighted regression was used to measure the association between a given psychosis birth-rate and a poliomyelitis epidemic during gestation. There was no statistically significant association between exposure to a poliomyelitis epidemic during gestation and subsequent development of schizophrenia or affective psychosis. The lack of a consistent statistically significant association between poliovirus epidemics and schizophrenia suggests that either poliovirus may have a small effect which is only detectable with large data-sets and/or the effect may be modified by location. Further investigation of such inconsistencies may help elucidate candidate risk-modifying factors for schizophrenia.
Publisher: MDPI AG
Date: 26-11-2021
DOI: 10.3390/NU13124254
Abstract: Preecl sia is a pregnancy disorder characterized by hypertension. Epidemiological studies have associated preecl sia with an increased risk of neurodevelopmental disorders in offspring, such as autism and schizophrenia. Preecl sia has also been linked with maternal vitamin D deficiency, another candidate risk factor also associated with autism. Our laboratory has established a gestational vitamin-D-deficient rat model that shows consistent and robust behavioural phenotypes associated with autism- and schizophrenia-related animal models. Therefore, we explored here whether this model also produces preecl sia as a possible mediator of behavioural phenotypes in offspring. We showed that gestational vitamin D deficiency was not associated with maternal blood pressure or proteinuria during late gestation. Maternal and placental angiogenic and vasculogenic factors were also not affected by a vitamin-D-deficient diet. We further showed that exposure to low vitamin D levels did not expose the placenta to oxidative stress. Overall, gestational vitamin D deficiency in our rat model was not associated with preecl sia-related features, suggesting that well-described behavioural phenotypes in offspring born to vitamin-D-deficient rat dams are unlikely to be mediated via a preecl sia-related mechanism.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2020
DOI: 10.1038/S41398-020-0688-Y
Abstract: Motivated by observational studies that report associations between schizophrenia and traits, such as poor diet, increased body mass index and metabolic disease, we investigated the genetic contribution to dietary intake in a s le of 335,576 in iduals from the UK Biobank study. A principal component analysis applied to diet question item responses generated two components: Diet Component 1 (DC1) represented a meat-related diet and Diet Component 2 (DC2) a fish and plant-related diet. Genome-wide association analysis identified 29 independent single-nucleotide polymorphisms (SNPs) associated with DC1 and 63 SNPs with DC2. Estimated from over 35,000 3rd-degree relative pairs that are unlikely to share close family environments, heritabilities for both DC1 and DC2 were 0.16 (standard error (s.e.) = 0.05). SNP-based heritability was 0.06 (s.e. = 0.003) for DC1 and 0.08 (s.e = 0.004) for DC2. We estimated significant genetic correlations between both DCs and schizophrenia, and several other traits. Mendelian randomisation analyses indicated a negative uni-directional relationship between liability to schizophrenia and tendency towards selecting a meat-based diet (which could be direct or via unidentified correlated variables), but a bi-directional relationship between liability to schizophrenia and tendency towards selecting a fish and plant-based diet consistent with genetic pleiotropy.
Publisher: MDPI AG
Date: 10-12-2021
DOI: 10.3390/IJNS7040082
Abstract: Neonatal dried blood spots (DBS) provide a remarkable resource for biobanks. These micros les can provide information related to the genetic correlates of disease and can be used to quantify a range of analytes, such as proteins and small molecules. However, after routine neonatal screening, the amount of DBS s le available is limited. To optimize the use of these s les, there is a need for sensitive assays which are integrated across different analytic platforms. For ex le, after DNA extraction, protein extracts are available for additional analyses. We describe a sensitive and robust LC-MS/MS method for 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 optimized for leftover protein extracts from DBS, which has excellent recovery, precision, and accuracy.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.NEULET.2009.05.070
Abstract: There is growing evidence that low vitamin D impacts adversely on brain development. The current study investigated the impact of developmental vitamin D (DVD) deficiency on dopamine and serotonin metabolism in the neonatal rat brain. DVD-deficiency resulted in an altered dopaminergic metabolic profile in the forebrain, with a decrease in the conversion of dihydroxyphenylacetic acid (DOPAC) to homovanillic acid (HVA). Correspondingly, expression of the enzyme required for this conversion, catechol-O-methyl transferase (COMT), was decreased. These results suggest that DVD-deficiency influences dopamine turnover during development.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.JSBMB.2006.12.096
Abstract: Epidemiology has highlighted the links between season of birth, latitude and the prevalence of brain disorders such as multiple sclerosis and schizophrenia. In line with these data, we have hypothesized that "imprinting" with low prenatal vitamin D could contribute to the risk of these two brain disorders. Previously, we have shown that transient developmental hypovitaminosis D induces permanent changes in adult nervous system. The aim of this study was to examine the impact of prenatal hypovitaminosis D on gene expression in the adult rat brain. Vitamin D deficient female rats were mated with undeprived males and the offspring were fed with a control diet after birth. At Week 10, gene expression in the progeny's brain was compared with control animals using Affymetrix gene microarrays. Prenatal hypovitaminosis D causes a dramatic dysregulation of several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, post-translational modifications, synaptic plasticity and neurotransmission. A computational analysis of these data suggests that impaired synaptic network may be a consequence of mitochondrial dysfunction. Since disruptions of mitochondrial metabolism have been associated with both multiple sclerosis and schizophrenia, developmental vitamin D deficiency may be a heuristic animal model for the study of these two brain diseases.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Frontiers Media SA
Date: 13-03-2019
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JSBMB.2015.09.018
Abstract: Population-based studies have confirmed that the prevalence of vitamin D deficiency is substantial in many societies, and is of particular concern in pregnant women. Vitamin D deficiency during pregnancy is associated with a wide range of adverse maternal and offspring health outcomes. To date, studies of vitamin D deficiency during pregnancy have focused on measurements at one or two time points in isolation. We examined both midgestation and cord blood 25 hydroxyvitamin D (25OHD) concentration and explored the prevalence and correlates of vitamin D deficiency in a large ethnically erse cohort of pregnant women and their infants in the Netherlands. This study was embedded in the Generation R Study, a population-based prospective cohort from fetal life onwards in Rotterdam, The Netherlands. Using a highly sensitive tandem mass spectroscopy-based assay, we measured 25OHD in 7256 midgestation s les (mean gestation 20.6 weeks) and 5023 neonatal cord blood s les (mean gestation 40.0 weeks). Using a conservative threshold of less than 25nmol/L to define vitamin D deficiency, we examined the prevalence and socio-demographic correlates of vitamin D deficiency in mothers and infants. We also derived a measure of vitamin D deficiency based on the two time points in order to explore persistent vitamin D deficiency in mother-infant pairs. The prevalence of vitamin D deficiency at midgestation was 26%, while in neonates 46% were deficient. 21% of the mother-infant pairs had persistent vitamin D deficiency (i.e., deficient in maternal and cord s les) and an additional 29% were vitamin D deficient in one of the two s les only. Persistent vitamin D deficiency was strongly associated with non-European ancestry and spring birth. A sizeable proportion of women and their neonatal offspring in the Generation R cohort were vitamin D deficient. In light of the large body of evidence linking vitamin D deficiency with adverse health outcomes for pregnant women and their offspring, our findings indicate a large unmet need in this population. In particular, women and infants from non-European ethnic background are at high risk of vitamin D deficiency.
Publisher: Cambridge University Press (CUP)
Date: 08-07-2008
DOI: 10.1017/S0033291708003760
Abstract: Birth cohort studies have shown that in iduals who develop non-affective psychoses display subtle deviations in behaviour during childhood and adolescence. We had the opportunity to examine the widely used Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR) to explore the antecedents of non-affective psychosis. Based on a birth cohort of 3801 young adults, psychopathology was assessed at years 5 and 14 using the CBCL and/or the YSR. Screen-positive non-affective psychosis (SP-NAP) was assessed at year 21 by using the Composite International Diagnostic Interview (CIDI) or a self-report checklist. The association between childhood symptoms and SP-NAP was examined using logistic regression. Of the cohort, 60 subjects were classified as SP-NAP. In males, SP-NAP was associated with higher scores: ( a ) on year 5 CBCL ‘Total’, ‘Aggression’ and ‘Social, Attention and Thought’ scores ( b ) on year 14 CBCL ‘Social’, ‘Attention’ and ‘Delinquency’ scores, and ( c ) YSR ‘Total’ and many YSR subscores. These associations were less clear for females. Hallucinations at year 14 were associated with SP-NAP for both sexes. Boys with high ‘Total’ scores at both years 5 and 14 were at greatest risk of SP-NAP (a 5-fold risk), followed by boys and girls whose ‘Social, Attention and Thought’ scores either increased or remained high from years 5 to 14 (3- to 13-fold risk). In iduals who screen positive for non-affective psychosis show increased psychopathology during childhood and adolescence. The psychopathological trajectory of children who go on to develop schizophrenia anticipates the heterogeneity associated with the full clinical syndrome.
Publisher: Wiley
Date: 09-12-2019
DOI: 10.1111/ADD.14482
Publisher: Wiley
Date: 16-02-2018
DOI: 10.1111/ACPS.12859
Publisher: Cambridge University Press (CUP)
Date: 25-04-2018
DOI: 10.1017/S0007114518000879
Abstract: Studies have suggested that vitamin D status at birth may be associated with a range of neonatal outcomes. The aim of this study was to assess the association between neonatal 25-hydroxyvitamin D 3 (25(OH)D 3 ) concentration and gestational age, birth weight, Ponderal Index and size for gestational age. Neonatal capillary blood stored as dried blood spots was used to assess 25(OH)D 3 concentrations among 2686 subjects selected from a random population sub-s le of in iduals, born in Denmark from 1 May 1981 to 31 December 2002. There was an inverse association between 25(OH)D 3 concentration and gestational age at birth of −0·006 (95 % CI −0·009, −0·003, P ·001) weeks of gestation per 1 nmol/l increase in 25(OH)D 3 concentration. An inverted U-shaped association between 25(OH)D 3 and birth weight and Ponderal Index ( P =0·04) was found, but no association with size for gestational age was shown. This study suggests that neonatal 25(OH)D 3 concentration is associated with anthropometric measures at birth known to be correlated with many subsequent health outcomes such as obesity and type 2 diabetes.
Publisher: Wiley
Date: 11-1994
DOI: 10.1111/J.1600-0447.1994.TB01607.X
Abstract: A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects.
Publisher: SAGE Publications
Date: 03-1995
DOI: 10.3109/00048679509075888
Abstract: Over the last five years a body of literature has been generated concerning whether or not prenatal exposure to influenza results in an increased risk of developing schizophrenia in the exposed offspring. The studies are reviewed with respect to the traditional epidemiological criteria that help to define causality. There is a modest degree of consistency in support of an association between the 1957 influenza epidemic — and less so, for influenza epidemics in general — and later schizophrenia. Two cohort studies examining the 1957 epidemic do not support an association. The strength and specificity of the association remain weak. The proposed association draws coherence from the neurodevelopmental hypothesis of schizophrenia. Suggestions are made for future research that could add to our understanding of the putative association between influenza and schizophrenia.
Publisher: AMPCo
Date: 06-2012
DOI: 10.5694/MJA11.10301
Abstract: The prevalence of vitamin D deficiency varies, with the groups at greatest risk including housebound, community-dwelling older and/or disabled people, those in residential care, dark-skinned people (particularly those modestly dressed), and other people who regularly avoid sun exposure or work indoors. Most adults are unlikely to obtain more than 5%-10% of their vitamin D requirement from dietary sources. The main source of vitamin D for people residing in Australia and New Zealand is exposure to sunlight. A serum 25-hydroxyvitamin D (25-OHD) level of ≥ 50 nmol/L at the end of winter (10-20 nmol/L higher at the end of summer, to allow for seasonal decrease) is required for optimal musculoskeletal health. Although it is likely that higher serum 25-OHD levels play a role in the prevention of some disease states, there is insufficient evidence from randomised controlled trials to recommend higher targets. For moderately fair-skinned people, a walk with arms exposed for 6-7 minutes mid morning or mid afternoon in summer, and with as much bare skin exposed as feasible for 7-40 minutes (depending on latitude) at noon in winter, on most days, is likely to be helpful in maintaining adequate vitamin D levels in the body. When sun exposure is minimal, vitamin D intake from dietary sources and supplementation of at least 600 IU (15 µg) per day for people aged ≤ 70 years and 800 IU (20 µg) per day for those aged > 70 years is recommended. People in high-risk groups may require higher doses. There is good evidence that vitamin D plus calcium supplementation effectively reduces fractures and falls in older men and women.
Publisher: Cambridge University Press (CUP)
Date: 03-08-2016
DOI: 10.1017/S0033291716001665
Abstract: Although mental disorders are significant predictors of educational attainment throughout the entire educational career, most research on mental disorders among students has focused on the primary and secondary school years. The World Health Organization World Mental Health Surveys were used to examine the associations of mental disorders with college entry and attrition by comparing college students ( n = 1572) and non-students in the same age range (18–22 years n = 4178), including non-students who recently left college without graduating ( n = 702) based on surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle at the times of two different surveys, and 11 high income). Lifetime and 12-month prevalence and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were assessed with the Composite International Diagnostic Interview (CIDI). One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders 83.1% of these cases had pre-matriculation onsets. Disorders with pre-matriculation onsets were more important than those with post-matriculation onsets in predicting subsequent college attrition, with substance disorders and, among women, major depression the most important such disorders. Only 16.4% of students with 12-month disorders received any 12-month healthcare treatment for their mental disorders. Mental disorders are common among college students, have onsets that mostly occur prior to college entry, in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated. Detection and effective treatment of these disorders early in the college career might reduce attrition and improve educational and psychosocial functioning.
Publisher: Wiley
Date: 02-06-2019
DOI: 10.1111/ADD.14599
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: SAGE Publications
Date: 22-11-2014
Abstract: The aim of this study was to model estimates related to (a) the incidence of psychotic disorders and (b) the mortality associated with these disorders based on a large, population-based prevalence study. Data were drawn from the second national survey of adults with psychotic disorders conducted in seven Australian catchment areas during March to December 2010. To generate incidence rate estimates, we identified recent onset cases recruited as part of the prevalence study and then imputed population-based incidence rates using a set of conservative assumptions. Similarly, for mortality rates, we identified in iduals who had died after being identified as ‘screen-positive’ for psychosis, but prior to full clinical assessment. Using a set of conservative assumptions, we then used these estimates to infer population-based mortality rates. Based on our models, we estimated that the incidence rate for psychotic disorders was 28 cases per 100,000 population. The rate estimates were significantly higher in males than females, with an overall male:female ratio of 1.57:1. Incidence rate estimates peaked in the youngest age group (18–24 years). The adjusted mortality rate estimated during the whole period of observation was 12.5 per 1000 persons, with a standardised mortality ratio of 5.5. Using treated prevalence data and observed deaths with appropriate algorithms, we were able to impute incidence and mortality rates for psychotic disorders consistent with the published literature. While the second national survey of psychotic disorders was not designed to identify mortality, our estimates provide a stark reminder of the increased mortality associated with these disorders.
Publisher: Cambridge University Press (CUP)
Date: 06-06-2014
DOI: 10.1017/S0033291714001378
Abstract: As one would expect for a heterogeneous syndrome like schizophrenia, at the in idual level the course of symptoms and disability vary widely. Mindful that the definition of recovery/remission varies widely between studies, a recent systematic review and meta-analysis reported that the proportion of those with schizophrenia who recover on both symptom and functional outcome is modest (approximately 14%). A 10-year follow-up of the English multicentre AESOP incidence study provides more ‘fine-grained’ insights into the time course of symptom fluctuation for schizophrenia and other psychotic disorders. We highlight selected findings from the new study and speculate on the role of different outcome domains for future study (e.g. symptom, occupational/functional, cognition, physical health, patient-nominated outcomes). Because recovery is a multifaceted process, we need to develop a panel of practical and operationalizable criteria for remission and recovery.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2022
Publisher: Elsevier BV
Date: 04-2004
Publisher: American Psychiatric Association Publishing
Date: 06-2013
Publisher: Wiley
Date: 28-03-2021
DOI: 10.1111/BDI.13066
Abstract: To examine patterns and predictors of perceived treatment helpfulness for mania/hypomania and associated depression in the WHO World Mental Health Surveys. Face‐to‐face interviews with community s les across 15 countries found n = 2,178 who received lifetime mania/hypomania treatment and n = 624 with lifetime mania/hypomania who received lifetime major depression treatment. These respondents were asked whether treatment was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Patterns and predictors of treatment helpfulness were examined separately for mania/hypomania and depression. 63.1% (mania/hypomania) and 65.1% (depression) of patients reported ever receiving helpful treatment. However, only 24.5–22.5% were helped by the first professional seen, which means that the others needed to persist in help seeking after initial unhelpful treatments in order to find helpful treatment. Projections find only 22.9% (mania/hypomania) and 43.3% (depression) would persist through a series of unhelpful treatments but that the proportion helped would increase substantially if persistence increased. Few patient‐level significant predictors of helpful treatment emerged and none consistently either across the two components (i.e., provider‐level helpfulness and persistence after earlier unhelpful treatment) or for both mania/hypomania and depression. Although prevalence of treatment was higher in high‐income than low/middle‐income countries, proportional helpfulness among treated cases was nearly identical in the two groups of countries. Probability of patients with mania/hypomania and associated depression obtaining helpful treatment might increase substantially if persistence in help‐seeking increased after initially unhelpful treatments, although this could require seeing numerous additional treatment providers. In addition to investigating reasons for initial treatments not being helpful, messages reinforcing the importance of persistence should be emphasized to patients.
Publisher: Elsevier BV
Date: 05-1996
DOI: 10.1016/0920-9964(95)00087-9
Abstract: Epidemiological studies often use age-of-first-admission from psychiatric case registers to estimate age-of-onset in schizophrenia. Retrospective, interview-based methods have shown that there is a delay between onset of symptoms and eventual contact with psychiatric services, and that this delay can vary both among in iduals and at different ages. This delay or lag can confound the interpretation of first admission data such as age-of-onset. To evaluate the potential impact of this factor, we constructed a flexible mathematical model which integrates age-at-first-admission with estimates of this lag, which were derived from interview-based studies and clinical judgement. We applied this model to age-of-first-admission data for 4218 patients with ICD8/9 schizophrenia drawn from a state-wide psychiatric register. Both the raw age-of-first-admission distribution curve and the transformed data ('estimated age-of-onset') reinforce previous findings that (a) there is a wide range of age-of-onset and (b) the shapes of the curves differ between the sexes. Inspection of the mathematically derived distribution supports the proposition that (a) transformation for a lag effect produces a lower onset age and (b) including a variable length of lag produces a change in shape of the distribution. We propose that the mathematical transformation of age-of-first-admission data may have heuristic value, but requires further empirical data on which to base the assumptions of the model.
Publisher: American Medical Association (AMA)
Date: 08-2020
Publisher: American Medical Association (AMA)
Date: 06-2020
Publisher: Oxford University Press (OUP)
Date: 14-05-2008
Abstract: Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7-43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born in iduals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.
Publisher: Cambridge University Press (CUP)
Date: 19-06-2017
DOI: 10.1017/S0033291717001660
Abstract: The beneficial effects of physical activity (PA) for both physical and mental wellbeing are well established. Given that adolescence presents a critical developmental period during which life-long patterns of PA become established, the exploration of the longitudinal impact of adolescent psychopathology on adult PA status is of interest. We analysed prospective data from 3663 young adults who participated in the Mater-University of Queensland Study of Pregnancy. Psychopathology was measured using the Youth Self-Report (YSR) at age 14. Participants’ engagement in three types of PA (vigorous exercise, moderate exercise and walking) at age 21 were dichotomised into either ‘none’ or ‘any’. For our main analysis, we examined the association between the YSR score and subsequent PA engagement using logistic regression. We also conducted sensitivity analyses of longitudinal associations between the YSR internalising and externalising symptoms score at age 14 and PA engagement at age 21. We found no longitudinal association between the total YSR score at age 14 and PA engagement at age 21. In addition, there was no longitudinal association between the YSR internalising or externalising symptoms and PA engagement. Our findings suggest that there is no longitudinal association between adolescent psychopathology and PA in young adulthood.
Publisher: Wiley
Date: 09-02-2017
DOI: 10.1111/ACPS.12708
Publisher: Springer Science and Business Media LLC
Date: 10-11-2016
DOI: 10.1007/S00127-016-1307-3
Abstract: To explore the association between histories of common mental disorders, delusional-like experiences, and recent physical activity using a large nationally representative population-based s le from Australia. We predicted that a past history of a common mental disorder or delusional-like experiences would be associated with insufficient physical activity. The study was based on the Australian National Survey of Mental Health and Wellbeing 2007 (n = 8841). The Composite International Diagnostic Interview was used to identify a lifetime and past year history of common mental disorders and delusional-like experiences. Physical activity over the preceding week was estimated using the questions based on the Active Australia survey with respondents classified as (a) insufficiently physically active versus (b) sufficiently physically active based on national recommendations. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors. Almost half of the participants (46.0%) were classified as sufficiently physically active. Compared to those with no past mental disorder, those with lifetime or past year history of common mental disorders did not differ on recent physical activity status. Furthermore, we found no significant association between the number of lifetime mental disorders or the presence of delusional-like experience and recent physical activity status. Our findings suggest that a diagnosis of common mental disorder, with or without recent symptoms and comorbid diagnoses, or even having self-ascribed perception of poor mental well-being, is not associated with insufficient physical activity.
Publisher: Wiley
Date: 21-02-2018
DOI: 10.1111/ADD.14145
Publisher: Royal College of Psychiatrists
Date: 03-2017
DOI: 10.1192/BJPO.BP.116.004077
Abstract: There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood. To determine the association between gestational vitamin D status and ASD. Based on a birth cohort ( n =4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records n =68 cases). In iduals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P =0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only. Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.
Publisher: MDPI AG
Date: 27-05-2019
DOI: 10.3390/NU11051187
Abstract: Emerging evidence suggests that gestational or developmental vitamin D (DVD) deficiency is associated with an increased risk of autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impairments in social interaction, lack of verbal and non-verbal communications, stereotyped repetitive behaviors and hyper-activities. There are several other clinical features that are commonly comorbid with ASD, including olfactory impairments, anxiety and delays in motor development. Here we investigate these features in an animal model related to ASD—the DVD-deficient rat. Compared to controls, both DVD-deficient male and female pups show altered ultrasonic vocalizations and stereotyped repetitive behavior. Further, the DVD-deficient animals had delayed motor development and impaired motor control. Adolescent DVD-deficient animals had impaired reciprocal social interaction, while as adults, these animals were hyperactive. The DVD-deficient model is associated with a range of behavioral features of interest to ASD.
Publisher: Springer Science and Business Media LLC
Date: 09-09-2023
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
Publisher: Oxford University Press (OUP)
Date: 18-08-2015
DOI: 10.1093/IJE/DYV136
Publisher: SAGE Publications
Date: 26-06-2012
Publisher: Wiley
Date: 06-1999
DOI: 10.1111/J.1600-0447.1999.TB00990.X
Abstract: Previous research has suggested that patients with schizophrenia have fewer offspring compared to the general population. Reduced fertility in a disorder with a strong genetic component and an apparently stable incidence has implications for models of genetic transmission. There is also a need to obtain contemporary estimates of the prevalence of parenthood among subjects with psychotic disorders in order to inform service planning. The aim of this study was to determine the fertility and fecundity of a representative s le of in iduals with psychoses who were in contact with mental health services, and to explore the interactions between age at first diagnosis and fertility. All clients of two community mental health clinics and an extended-care psychiatric hospital were surveyed. Data on diagnosis, age at first diagnosis, and the number and age of offspring were collected. Based on interviews with the proband and chart review, a genogram of the probands' family was drawn that identified sex, age, affected status and the number of offspring for each patient and their siblings. In total, 36% of all patients were parents. Most women with psychoses (59%) were mothers. Patients with psychoses had fewer offspring compared to their unaffected same-sex siblings. This was especially the case for men with non-affective psychoses. Higher levels of fertility were associated with a later age at first diagnosis. The consistent finding of reduced 'reproductive fitness' in those with non-affective psychoses needs to be incorporated in the genetic epidemiology of these disorders. Despite this reduction in fertility and fecundity, many patients with psychoses are parents. Services need to remain mindful of the special needs of these patients.
Publisher: Wiley
Date: 09-10-2018
DOI: 10.1111/GBB.12522
Abstract: Advanced paternal age (APA) is associated with an increased risk of adverse health outcomes in offspring, including autism and schizophrenia. In the present study, we investigated the behaviour of young (3-month-old Control), middle aged (12 to 15-month-old APA1) and old (24-month-old APA2) C57BL/6J sires and their adult offspring. Male and female mice were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding and for prepulse inhibition of the acoustic startle response. Increasing the APA sire age to 24 months was shown to be associated with increased anxiety-related behaviour in the offspring, and indicated that increasing APA sire age produced a more robust hypoexplorative phenotype. Thus, increasing paternal age was associated with an increase in severity of an anxiogenic phenotype in their adult offspring. Ultimately, the results of these studies show that mouse models of APA are valuable for elucidating the mechanisms by which APA influences brain-related outcomes.
Publisher: John Wiley & Sons, Ltd
Date: 18-07-2007
Publisher: Public Library of Science (PLoS)
Date: 16-06-2022
DOI: 10.1371/JOURNAL.PMED.1004023
Abstract: The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified in iduals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site ( tlas ) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.
Publisher: Wiley
Date: 28-10-2015
Publisher: Cambridge University Press (CUP)
Date: 26-07-2012
DOI: 10.1017/S2040174412000542
Abstract: During foetal development, calcium requirements are met as a consequence of maternal adaptations independent of vitamin D status. In contrast, after birth, dependency on vitamin D appears necessary for calcium metabolism and skeletal health. We used a rodent model (Sprague-Dawley rats), to determine if maternal vitamin D deficiency during pregnancy had a deleterious effect on bone structure at birth. Vitamin D deplete females were maintained under deplete conditions until birth of the pups, whereupon all dams were fed a vitamin D replete diet. Offspring were harvested at birth, and 140 days of age. Bones were analyzed using micro-computed tomography and strength tested to study differences in bone structure, density and strength and subjected to elemental analysis using plasma mass spectrometry to determine strontium, barium and calcium contents. Offspring from deplete mothers displayed altered trabecular parameters in the femur at birth and 140 days of age. In addition, at 140 days of age there was evidence of premature mineralization of the secondary ossification centre of the femoral head. Elemental analysis showed increased strontium uptake in the femur of the developmentally vitamin D-deficient offspring. Vitamin D depletion during development in the offspring may have a long-lasting effect, despite repletion of vitamin D from birth. This may have consequences for human health given the low vitamin D levels seen during pregnancy and current lifestyle of sun avoidance due to the risk of skin cancer.
Publisher: Oxford University Press (OUP)
Date: 15-08-2003
DOI: 10.1093/AJE/KWG119
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1996
Publisher: American Psychological Association (APA)
Date: 2016
DOI: 10.1037/PRJ0000185
Abstract: The aim of this secondary analysis was to explore global functioning, course of illness (the number of episodes since onset and the degree of recovery between episodes), duration of illness, and cognitive ability as potential indicators of the extent of employment assistance needs. A secondary analysis of Australia's second national survey of psychosis was undertaken. Screening for psychosis took place during March, 2010 at 7 national locations, within public mental health services and nongovernment organizations. Next, 1,825 of the 7,955 who screened positive for psychosis were randomly selected and completed face-to-face interviews. Of those, 1,619 also completed the Digit Symbol Coding Test (DSCT), a measure of current general cognitive ability. In epidemiological surveys, employment status is an important proxy indicator of employment assistance needs. The strongest correlates of any versus no employment in the current survey were: global functioning as represented by Personal and Social Performance Scale (PSP) total score, age, general cognitive ability as represented by DSCT scores, course of illness, and educational attainment. These correlates persisted following adjustment in a multivariate model. Subject to the limitations identified, global functioning, cognitive ability, and course of illness were the most promising clinical and cognitive indicators of more intensive employment assistance needs. The demographic variables age and educational attainment indicated additional labor market disadvantage, which could also help to identify those more likely to need intensive employment assistance. These results inform further investigations aimed at developing a practical measure of employment-related psychiatric disability. (PsycINFO Database Record
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/03014460500154699
Abstract: Birth weight is known to fluctuate with month of birth and with latitude however the mechanisms underlying these gradients remain unclear. The study examined within-year fluctuations in birth weight across four regions in Australia. We obtained the birth weight of singleton births of at least 37 weeks gestation from four regions: (a) southeast Queensland, (b) Sydney and surrounding districts, (c) Victoria, and (d) Tasmania. Seasonal fluctuations were examined after long-term trends had been removed. The litude, timing and variability of seasonal fluctuations were examined and compared across regions. Each of the four regions had prominent annual periodicity with the peak birth weight occurring in spring. The litude of this signal ranged from 1.4 g (Victoria) to 7.7 g (southeast Queensland). There was no significant correlation between the litude of these fluctuations and the latitude of four regions. In addition, a second smaller autumn peak was identified. Environmental factors that have regular within-year variation influence birth weight in Australia. The evidence suggests that at least two distinguishable seasonal processes contribute to the findings. Identifying the factors underlying these seasonal fluctuations could have implications from a public health perspective.
No related grants have been discovered for John McGrath.