Psychiatry - Research Publications
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ItemImpact of antipsychotic medication on IL-6/STAT3 signaling axis in peripheral blood mononuclear cells of drug-naive schizophrenia patients(WILEY, 2020-01)AIM: Immunopathogenesis remains a widely appreciated etiopathological model of schizophrenia. Persistent efforts have aimed to identify schizophrenia biomarkers indexing immune system abnormalities and also immuno-dampening effects of antipsychotic medications. Although data arising from published reports are encouraging, such studies are limited to a few immune parameters and not focused on a specific pathway. Th17 cells-mediated immuno-inflammatory responses have emerged as a potential mechanism in various neuropsychiatric conditions, including schizophrenia. The Th17 pathway is distinctly regulated through a coordinated action of multiple cytokines and transcription factors. In this study, we explored whether antipsychotic medication has any effect on the cytokines and transcription factors of the Th17 pathway. METHODS: A total of 27 drug-naive schizophrenia patients were recruited and followed up for 3 months after initiation of antipsychotic medication. Lymphocyte gene expression levels of two transcription factors (STAT3 and RORC) and one of their upstream regulators, IL6, were quantified before and after treatment. Plasma levels of cytokines, such as interleukin (IL)-1β, IL-6, IL-17A, IL-23, and IL-33, were also analyzed before and after treatment. RESULTS: Treatment with antipsychotic medication for 3 months resulted in significant downregulation of STAT3 gene expression as well as reduction in plasma levels of IL-1β, IL-6, and IL-17A. Significant reduction in total scores for the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms was also observed in schizophrenia patients after 3 months of antipsychotic treatment. CONCLUSION: Our findings suggest possible immuno-modulatory effects of antipsychotic medication on the critical regulators, such as IL-6 and STAT3, of the Th17 pathway in schizophrenia patients. The IL-6/STAT3 signaling axis involved in the transcriptional regulation of Th17 cells might appear as an important target of antipsychotic treatment in schizophrenia patients. Alternatively, irrespective of the effect of antipsychotic drugs, the IL-6/STAT3 signaling axis might be crucially involved in ameliorating psychotic symptoms.
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ItemThe 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: Major depression summary(WILEY, 2020-12)OBJECTIVES: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020 , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression. RESULTS: The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response. CONCLUSIONS: The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg2020 . The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.
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ItemThe 2020 Royal Australian and New Zealand College of psychiatrists clinical practice guidelines for mood disorders: Bipolar disorder summary(WILEY, 2020-12)OBJECTIVES: To provide a succinct, clinically useful summary of the management of bipolar disorder, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020 , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on bipolar disorder. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of bipolar disorder. RESULTS: The bipolar disorder summary provides a systematic approach to diagnosis, and a logical clinical framework for management. It addresses the acute phases of bipolar disorder (mania, depression and mixed states) and its longer-term management (maintenance and prophylaxis). For each phase it begins with Actions, which include important strategies that should be implemented from the outset wherever possible. These include for example, lifestyle changes, psychoeducation and psychological interventions. In each phase, the summary advocates the use of Choice medications for pharmacotherapy, which are then used in combinations along with additional Alternatives to manage acute symptoms or maintain mood stability and provide prophylaxis. The summary also recommends the use of electroconvulsive therapy (ECT) for each of the acute phases but not for maintenance therapy. Finally, it briefly considers bipolar disorder in children and its overlap in adults with borderline personality disorder. CONCLUSIONS: The bipolar disorder summary provides up to date guidance regarding the management of bipolar disorder, as set out in the MDcpg2020 . The recommendations are informed by evidence and clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians but will be of interest to anyone involved in the management of patients with bipolar disorder.
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ItemThe influence of stage of illness on functional outcomes after psychological treatment in bipolar disorder: A systematic review(WILEY, 2020-11)OBJECTIVES: The aim of this study was to advance understanding of stage of illness in bipolar disorder (BD), by interrogating the literature for evidence of an influence of stage of illness on functional (ie non-symptom) outcomes following psychosocial intervention. METHODS: A systematic literature search following PRISMA guidelines was conducted to identify empirical studies of psychosocial interventions for established BD. To investigate stage as a predictor of three functional outcomes (general/social functioning, cognitive functioning and quality of life [QoL]), study samples were dichotomised into earlier and later stage using proxy measures identified in existing staging models. Findings were integrated using data-based convergent synthesis. RESULTS: A total of 88 analyses from 62 studies were identified. Synthesis across studies suggested that psychosocial intervention was more likely to be effective for general functioning outcomes earlier in the course of established BD. No stage-related differences were found for cognitive or QoL outcomes. Exploratory investigations found some evidence of an interaction between specific intervention type and stage of illness in predicting outcomes. CONCLUSIONS: A novel systematic review provided preliminary evidence that benefits general/social functioning may be more pronounced in earlier versus later stages of established BD. The review also generated hypotheses about a potential three-way interaction, whereby specific psychosocial interventions may be best placed to target functional outcomes in earlier versus later stage BD. The strength of conclusions is limited by the overall low-quality and significant heterogeneity of studies. Further research is urgently required to understand the impact of illness stage on the effectiveness of psychosocial interventions.
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ItemRisk of dementia in bipolar disorder and the interplay of lithium: a systematic review and meta-analyses(WILEY, 2020-06)OBJECTIVES: To assess whether bipolar disorder (BD) increases the rate of dementia and whether lithium is related to a lower risk of dementia in BD. METHODS: A total of 10 studies (6859 BD; 487 966 controls) were included in the meta-analysis to test whether BD is a risk factor for dementia. In addition, five studies (6483 lithium; 43 496 non-lithium) were included in the meta-analysis about the potential protective effect of lithium in BD. RESULTS: BD increases the risk of dementia (odds ratio (OR): 2.96 [95% CI: 2.09-4.18], P < 0.001), and treatment with lithium decreases the risk of dementia in BD (OR: 0.51 [95% CI: 0.36-0.72], P < 0.0001). In addition, secondary findings from our systematic review showed that the risk of progression to dementia is higher in BD than in major depressive disorder (MDD). Moreover, the number of mood episodes predicted the development of dementia in BD. CONCLUSION: Individuals with BD are at higher risk of dementia than both the general population or those with MDD. Lithium appears to reduce the risk of developing dementia in BD.
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ItemEffect of Sodium Benzoate vs Placebo Among Individuals With Early Psychosis A Randomized Clinical Trial(AMER MEDICAL ASSOC, 2020-11-10)IMPORTANCE: There is evidence that sodium benzoate (BZ) may be an effective adjunctive treatment for schizophrenia. The clinical efficacy of BZ has been investigated in chronic schizophrenia; however, the efficacy of this agent has not been studied in individuals with early psychosis. OBJECTIVE: To examine the clinical efficacy of the adjunctive use of BZ for symptoms in people with early psychosis. DESIGN, SETTING, AND PARTICIPANTS: Using a placebo-controlled double-masked parallel-group design, this randomized clinical trial was conducted from August 2015 to July 2018. Participants aged between 15 and 45 years experiencing early psychosis were enrolled from 5 major clinical sites in Queensland, Australia. Data analysis was conducted from October 2018 to February 2020. INTERVENTIONS: Participants were randomized 1:1 (50 participants in each group) to receive 500 mg of sodium benzoate twice daily or placebo for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks. The key secondary efficacy measures were (1) the Clinical Global Impression score, (2) the Hamilton Depression Rating Scale for depression, (3) functioning as assessed by the clinician-rated Global Assessment of Function, and (4) the Assessment of Quality of Life Scale. The PANSS subscale scores and impact on selected amino acid concentrations were also assessed. RESULTS: The study comprised 100 participants with a mean (SD) age of 21.4 (4.1) years, of whom 73 (73%) were male individuals. The mean (SD) baseline PANSS score was 75.3 (15.4). We found no improvement in total PANSS score in the BZ group compared with the placebo group. The end result of least-squares mean difference (SE) for total PANSS was -1.2 (2.4) (P = .63). There were no differences in any subscales of the PANSS, any secondary measures, nor any amino acid concentrations. The dose of BZ was well tolerated without any clinically significant treatment-emergent adverse event differences between BZ and placebo groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, there was no evidence that adjunctive use of 500 mg of BZ twice daily is an effective treatment for individuals with early psychosis. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12615000187549.
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ItemNo Preview AvailableThe effect of emerging nutraceutical interventions for clinical and biological outcomes in multiple sclerosis: A systematic review(ELSEVIER SCI LTD, 2020-01)BACKGROUND: Due to the considerable burden of multiple sclerosis (MS)-related symptoms and the need to identify effective interventions to prevent disease progression, various nutraceutical interventions have been trialed as adjunctive treatments. The aim of this review was to investigate the efficacy and safety of nutraceutical interventions for clinical and biological outcomes in people with MS. METHODS: In accordance with PRISMA reporting guidelines, a systematic literature search was conducted using three electronic literature databases. Risk of bias was assessed using the Jadad scale. RESULTS: Thirty-seven randomized controlled trials, investigating fourteen nutraceuticals, were included in the review. Trials that investigated alpha lipoic acid (n = 4/6), ginkgo biloba (n = 3/5), vitamin A (n = 2/2), biotin (n = 1/2), carnitine (n = 1/2), green tea (n = 1/2), coenzyme Q10 (n = 1/1), probiotics (n = 1/1), curcumin (n = 1/1), Andrographis paniculata (n = 1/1), ginseng (n = 1/1), and lemon verbena (n = 1/1) were reported to improve biological (e.g. MRI brain volume change, antioxidant capacity) and/or clinical (e.g. fatigue, depression, Expanded Disability Status Scale) outcomes in multiple sclerosis compared to control. However, most trials were relatively small (average study sample size across included studies, n = 55) and there were few replicate studies per nutraceutical to validate the reported results. Furthermore, some nutraceuticals (e.g. green tea and inosine) should be used with caution due to reported adverse events. Risk of bias across most studies was low, with 31 studies receiving a score between 4 and 5 (out of 5) on the Jadad Scale. CONCLUSION: The existing literature provides preliminary support for the use of a number of nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as the gut microbiome and mitochondrial dysfunction. Prospero ID: CRD42018111736.
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ItemNo Preview AvailableExplanatory style in youth self-harm: an Indian qualitative study to inform intervention design(BMJ PUBLISHING GROUP, 2020-08)BACKGROUND: There are very few studies that have examined the effectiveness of psychological interventions (PIs) that have been developed and tested in high-income countries to reduce self-harm in low and middle-income countries. OBJECTIVE: To evaluate the perspectives and explanatory styles of youth with self-harm and their caregivers to inform the design of an evidence based PI in a non-Western cultural setting. An additional objective was to suggest ways of integrating local practices and traditions to enhance its acceptability. METHODS: We conducted 15 in-depth qualitative interviews with youth with self-harm and four interviews with the caregivers in the psychiatry department of a tertiary hospital located in Mumbai, India. Data were analysed using phenomenological thematic analysis. FINDINGS: Five themes were uncovered: (i) contextual factors related to self-harm including interpersonal factors, intrapersonal factors and socio-cultural factors; (ii) formulation and current feelings about the attempt (iii) family members and friends as the perceived supports and deterrents for future self-harm attempts; (iv) treatment related experiences with counselling, in-patient and outpatient treatment and barriers to treatment; and (v) coping strategies. Recommendations for key areas of adaptation include therapist adaptation, content adaptation to accommodate for cultural considerations and broader social context. Gender based socio-cultural norms, beliefs and stigma attached to self-harm need to be specifically addressed in South Asian setting. Interpersonal conflicts are the most common triggers. CONCLUSION AND CLINICAL IMPLICATIONS: To our knowledge this is the first study in the South Asian context evaluating explanatory styles of youth with self-harm and their caregivers to inform the design of an intervention to ensure its cultural congruence. Cultural adaptation of an evidence based PI results in competent delivery and ensures best results in diverse ethno-cultural populations.
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ItemNo Preview AvailableThe association of antihypertensive use and depressive symptoms in a large older population with hypertension living in Australia and the United States: a cross-sectional study(SPRINGERNATURE, 2020-11)Cardiovascular drugs impact many pathways involved in depression pathophysiology and treatment. However, their distinct impact on mood is underrecognized and the literature is conflicting. Therefore, using a very large and well-characterised sample of older adults with hypertension, we aimed to investigate the prevalence of depressive symptoms in users of different antihypertensive classes. We analysed baseline data from 14,195 older individuals with hypertension enroled in a large clinical trial. Median age was 75 years. The association of antihypertensive use by class and depression prevalence, as measured by a validated depression scale, was determined using logistic regression models. Multivariable logistic models were implemented to account for important confounding factors. Our analyses showed a positive association between depressive symptoms and the use of beta blockers (BB) (OR: 1.37; 95% CI: 1.17-1.60, p < 0.01), compared with users of other antihypertensive classes. All other classes of antihypertensives (including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers) were not significantly associated with depressive symptoms. In secondary analysis, this relationship was stronger for lipophilic (39%) and nonselective BB (52%) compared with hydrophilic (26%) and selective medications (31%), respectively. This study adds further evidence for a probable association between BB and depression in a large sample of older adults with hypertension and no history of cardiovascular disease or heart failure. These findings should regenerate interest and increase awareness of clinicians about the possible adverse effects of these medications in an otherwise healthy older population.
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ItemNo Preview AvailablePatterns of Association between Depressive Symptoms and Chronic Medical Morbidities in Older Adults(WILEY, 2020-08)OBJECTIVES: To investigate the association between depressive symptoms and several medical morbidities, and their combination, in a large older population. DESIGN: Cross-sectional study of baseline data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. SETTING: Multicentric study conducted in Australia and the United States. PARTICIPANTS: A total of 19,110 older adults (mean age = 75 years [standard deviation = ±4.5]). MEASUREMENTS: Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D 10) scale. Medical morbidities were defined according to condition-specific methods. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to test associations before and after accounting for possible confounders. RESULTS: Depressive symptoms were significantly associated with obesity (OR = 1.19; 95% CI = 1.07-1.32), diabetes (OR = 1.22; 95% CI = 1.05-1.42), gastroesophageal reflux disease (GERD) (OR = 1.41; 95% CI = 1.28-1.57), metabolic syndrome (OR = 1.16; 95% CI = 1.03-1.29), osteoarthritis (OR = 1.41; 95% CI = 1.27-1.57), respiratory conditions (OR = 1.25; 95% CI = 1.10-1.42), history of cancer (OR = 1.19; 95% CI = 1.05-1.34), Parkinson's disease (OR = 2.56; 95% CI = 1.83-3.56), polypharmacy (OR = 1.60; 95% CI = 1.44-1.79), and multimorbidity (OR = 1.29; 95% CI = 1.12-1.49). No significant association was observed between depressive symptoms and hypertension, chronic kidney disease, dyslipidemia, and gout (P > .05). A significant dose-response relationship was evident between the number of medical comorbidities and the prevalence of depression (OR = 1.18; 95% CI = 1.13-1.22). CONCLUSION: Late-life depressive symptoms are significantly associated with several medical morbidities, and there appears to be a cumulative effect of the number of somatic diseases on the prevalence of depression. These findings augment the evidence for a complex relationship between mental and physical health in an otherwise healthy older population and might guide clinicians toward early recognition of high-risk individuals. J Am Geriatr Soc 68:1834-1841, 2020.