ORCID Profile
0000-0003-3255-5118
Current Organisation
University of Adelaide
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Publisher: Oxford University Press (OUP)
Date: 03-12-2021
DOI: 10.1093/IJNP/PYAA092
Abstract: Partial response to antidepressant medication as well as relapse and treatment resistance are common in major depressive disorder (MDD). Therefore, for most patients with MDD, there will be a need to consider changing antidepressant medication at some stage during the course of the illness. The PREDDICT study investigates the efficacy of augmenting vortioxetine with celecoxib. We describe the method used in the PREDDICT study to change participants, who were already taking antidepressant medication at the time of the screening visit, to vortioxetine. We used a cross-titration to change study participants to vortioxetine. Of a total of 122 study participants who were randomized to receive vortioxetine plus celecoxib or vortioxetine plus placebo at the study baseline visit, 82 were taking antidepressant medication (other than vortioxetine) prior to randomization. These medications were selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, mirtazapine, or agomelatine. Eighty of these 82 participants completed the changeover to vortioxetine as well as the study baseline visit. We found side effects were generally mild during this changeover period. In addition, there was a reduction in mean total Montgomery-Åsberg Depression Rating Scale score of 2.5 (SD 6.0) from study baseline to week 2 and a further reduction in mean total Montgomery-Åsberg Depression Rating Scale of 2.5 (SD 5.9) from week 2 to week 4. Changing other antidepressants to vortioxetine can be done safely and was generally well-tolerated. However, there are some antidepressant classes, in particular monoamine oxidase inhibitors that require a washout period, which were not represented in this study. Australian New Zealand Clinical Trials Registry (ANZCTR) ID number 12617000527369p www.anzctr.org.au/ACTRN12617000527369p.aspx
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: Wiley
Date: 16-11-2020
DOI: 10.1111/CAMH.12434
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JPSYCHIRES.2017.07.006
Abstract: Lower levels of circulating iron have been associated with depression. Our objective was to investigate the phenotypic and genetic relationship between measures of circulating levels of iron (serum iron, transferrin, transferrin saturation, and ferritin) and depressive symptoms. Data were available from ongoing studies at QIMR Berghofer Medical Research Institute (QIMRB), including twin adolescents (mean age 15.1 years, standard deviation (SD) 3.2 years), and twin adults (mean age 23.2 years, SD 2.2 years). In the adolescent cohort, there were 3416 participants from 1688 families. In the adult cohort there were 9035 participants from 4533 families. We estimated heritabilities of, and phenotypic and genetic correlations between, traits. We conducted analyses that linked results from published large-scale genome-wide association studies (including iron and Major Depressive Disorder) with our study s les using single SNP and multi-SNP genetic risk score analyses, and LD score regression analyses. In both cohorts, measures of iron, transferrin, transferrin saturation, and log 10 of ferritin (L10Fer) were all highly heritable, while depressive measures were moderately heritable. In adolescents, depression measures were higher in those in the middle 10th versus top 10th percentile of transferrin saturation measures (p = 0.002). Genetic profile risk scores of the iron measures were not significantly associated with depression in study participants. LD score analyses showed no significant genetic relationship between iron and depression. Genetic factors strongly influence iron measures in adolescents and adults. Using several different strategies we find no evidence for a genetic contribution to the relationship between blood measures of iron and measures of depression.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2016
DOI: 10.1038/MP.2016.60
Publisher: Physicians Postgraduate Press, Inc
Date: 20-11-2018
DOI: 10.4088/JCP.18M12472
Publisher: Wiley
Date: 27-08-2023
DOI: 10.1111/JNC.15946
Abstract: Low‐grade inflammation is considered as a pathophysiological mechanism in a subtype of patients with major depressive disorder (MDD). Anti‐inflammatory drugs have shown efficacy in treating MDD. However, it remains unclear how to identify suitable patients for anti‐inflammatory treatment of depression. This study investigates the predictive value of pre‐treatment high‐sensitivity C‐Reactive Protein (hsCRP) stratification on the outcome of celecoxib augmentation of vortioxetine. The PREDDICT study was conducted as a randomized, double‐blind, placebo‐controlled 6‐week trial on augmentation of vortioxetine with celecoxib between December 2017 and April 2020 at the University of Adelaide (Australia). The present analysis focusses on the question of whether the pre‐treatment hsCRP measurement and stratification of patients to depression with inflammation (hsCRP mg/L) or without inflammation (hsCRP ≤3 mg/L) has an impact on the outcome of anti‐inflammatory treatment with celecoxib. A total of n = 119 mostly treatment‐resistant MDD patients with moderate to severe symptomatology were recruited in the trial. There was no effect of treatment group (celecoxib or placebo), pre‐treatment hsCRP strata (with/without inflammation), or interaction between the two terms on treatment outcome. The results of the current analysis do not support the hypothesis that pre‐treatment hsCRP level is predictive for response to anti‐inflammatory treatment with celecoxib in MDD patients. Further research is needed to identify appropriate biomarkers for the prediction of anti‐inflammatory treatment outcome in depression. image Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p .
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.PSYCHRES.2018.08.033
Abstract: Cognitive deficits are frequently observed in major depressive disorder (MDD), as well as impaired long-term psychosocial functioning. However, the relationship between cognitive deficits and psychosocial functioning in MDD is under-investigated. We aim to systematically review the literature on the relationship between specific cognitive impairments and psychosocial functioning in MDD. We systematically reviewed English-language literature in PubMed, PsychINFO, Scopus and Web of Science using search terms related to psychosocial functioning. Additional studies were identified by searching reference lists. Following our inclusion/exclusion criteria, 28 studies were reviewed. Inclusion criteria included age (> 18), MDD diagnosed by standard tools (e.g., DSM-IV), use of cognitive and psychosocial assessments. Cross-sectional studies indicated that cognitive deficits in domains of executive functioning, attention, memory, and global cognition are associated with psychosocial dysfunction in domains of as quality of life, and social, occupational, and global functioning. The cognition-functioning relationship was also observed in longitudinal studies, showing that only specific cognitive domains affected psychosocial outcomes over the long-term course of illness. Older age and greater MDD symptom severity appear to enhance cognition-psychosocial dysfunction relationship, however little is known regarding the role of a number of other clinical factors (e.g., psychosis, illness duration).
Publisher: Wiley
Date: 04-06-2013
DOI: 10.1111/JCPP.12080
Abstract: While cytokines have been implicated in the pathophysiology of depression in adults, the potential role in younger age groups such as adolescents is less clear. This article therefore reviews the literature (a) to explore the relationship between cytokines and depression in adolescents, and (b) to examine how cytokines may be related to adolescent depression in the context of other neurobiological theories of depression. A systematic review of the scientific literature on the subject was conducted in February 2013, searching the Web of Knowledge, PubMed (Medline), PsycInfo and Cochrane electronic databases. Eighteen studies were identified measuring both depression or depressive symptoms and cytokines or immune markers in adolescents. Adolescents with depression show age-specific characteristics of the immune and inflammatory system, specifically in NK cell activity and in pro-inflammatory cytokines (such as IL-1β and TNF-α). In addition, the role of cytokines in adolescent depression is influenced by neurodevelopment, hormonal changes, stress and trauma. There may be differences in the neurobiology of adolescent major depressive disorder (MDD) compared with adult MDD. Increased understanding of the role of cytokines in adolescent MDD may lead to improved outcomes in the treatment of adolescent depression.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2018
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/BMJOPEN-2020-046830
Abstract: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).
Publisher: Springer Science and Business Media LLC
Date: 02-05-2017
DOI: 10.1038/TP.2017.84
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: 15-11-2021
Publisher: Wiley
Date: 21-11-2017
DOI: 10.1002/AJMG.B.32593
Publisher: Cold Spring Harbor Laboratory
Date: 03-10-2018
DOI: 10.1101/433946
Abstract: Female reproductive behaviors have an important implication in evolutionary fitness and health of offspring. Previous studies have shown that age at first birth of women (AFB) is genetically associated with schizophrenia (SCZ). However, for most other psychiatric disorders and reproductive traits, the latent shared genetic architecture is largely unknown. Here we used the second wave of UK Biobank data (N=220,685) to evaluate the association between five female reproductive traits and polygenetic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N=429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with AFB (genetic correlation of −0.68 ± 0.03 with p-value = 1.86E-89), age at first sexual intercourse (AFS) (−0.56 ± 0.03 with p-value = 3.42E-60), number of live births (NLB) (0.36 ± 0.04 with p-value = 4.01E-17) and age at menopause (−0.27 ± 0.04 with p-value = 5.71E-13). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (genetic correlation of 0.35 ± 0.06), ED and AFS (0.19 0.06), Major depressive disorder (MDD) and AFB (−0.27 ± 0.07), MDD and AFS (− 0.27 ± 0.03) and SCZ and AFS (−0.10 ± 0.03). Our findings reveal the shared genetic architecture between the five reproductive traits in women and six psychiatric disorders, which have a potential implication that helps to improve reproductive health in women, hence better child outcomes. Our findings may also explain, at least in part, an evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.
Publisher: Springer Science and Business Media LLC
Date: 30-06-2015
DOI: 10.1038/MP.2015.69
No related grants have been discovered for Natalie Mills.