Psychiatry - Research Publications

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    Clinical and demographic characteristics of people who smoke versus inject crystalline methamphetamine in Australia: Findings from a pharmacotherapy trial
    McKetin, R ; Quinn, B ; Higgs, P ; Berk, M ; Dean, OM ; Turner, A ; Kelly, PJ ; Lubman, D ; Carter, G ; Baker, AL ; Manning, V ; Thomas, T ; Bathish, R ; Raftery, D ; Saunders, L ; Wrobel, A ; Meehan, A ; Sinclair, B ; Reid, D ; Arunogiri, S ; Hill, H ; Cordaro, F ; Dietze, PM (WILEY, 2021-11-01)
    INTRODUCTION AND AIMS: There has been a rapid increase in smoking crystalline methamphetamine in Australia. We compare the clinical and demographic characteristics of those who smoke versus inject the drug in a cohort of people who use methamphetamine. DESIGN AND METHODS: Participants (N = 151) were dependent on methamphetamine, aged 18-60 years, enrolled in a pharmacotherapy trial for methamphetamine dependence, and reported either injecting (n = 54) or smoking (n = 97) methamphetamine. Measures included the Timeline Followback, Severity of Dependence Scale, Amphetamine Withdrawal Questionnaire, Craving Experience Questionnaire and the Brief Psychiatric Rating Scale (symptoms of depression, hostility, psychosis and suicidality). Simultaneous regression was used to identify independent demographic correlates of smoking methamphetamine and to compare the clinical characteristics of participants who smoked versus injected. RESULTS: Compared to participants who injected methamphetamine, those who smoked methamphetamine were younger and less likely to be unemployed, have a prison history or live alone. Participants who smoked methamphetamine used methamphetamine on more days in the past 4 weeks than participants who injected methamphetamine (26 vs. 19 days, P = 0.001); they did not differ significantly in their severity of methamphetamine dependence, withdrawal, craving or psychiatric symptoms (P > 0.05). After adjustment for demographic differences, participants who smoked had lower craving [b (SE) = -1.1 (0.5), P = 0.021] and were less likely to report psychotic symptoms [b (SE) = -1.8 (0.7), P = 0.013] or antidepressant use [b (SE) = -1.1 (0.5), P = 0.022]. DISCUSSION AND CONCLUSIONS: Smoking crystalline methamphetamine is associated with a younger less marginalised demographic profile than injecting methamphetamine, but a similarly severe clinical profile.
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    Effect of Sodium Benzoate vs Placebo Among Individuals With Early Psychosis A Randomized Clinical Trial
    Scott, JG ; Baker, A ; Lim, CCW ; Foley, S ; Dark, F ; Gordon, A ; Ward, D ; Richardson, D ; Bruxner, G ; Beckmann, KM ; Hatherill, S ; Stathis, S ; Dixon, K ; Ryan, AE ; McWhinney, BC ; Ungerer, JPJ ; Berk, M ; Dean, OM ; Saha, S ; McGrath, J (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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    Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial
    Kavanagh, BE ; Williams, LJ ; Berk, M ; Turner, A ; Jackson, HJ ; Mohebbi, M ; Kanchanatawan, B ; Ashton, MM ; Ng, CH ; Maes, M ; Berk, L ; Malhi, GS ; Dowling, N ; Singh, AB ; Dean, OM (ASSOC BRASILEIRA PSIQUIATRIA, 2020-01-01)
    OBJECTIVE: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). METHODS: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. RESULTS: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). CONCLUSION: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. CLINICAL TRIAL REGISTRATION: ACTRN12612000283875.
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    Studies on Haloperidol and Adjunctive alpha-Mangostin or Raw Garcinia mangostana Linn Pericarp on Bio-Behavioral Markers in an Immune-Inflammatory Model of Schizophrenia in Male Rats
    Lotter, J ; Moller, M ; Dean, O ; Berk, M ; Harvey, BH (FRONTIERS MEDIA SA, 2020-03-31)
    Schizophrenia is a severe brain disorder that is associated with neurodevelopmental insults, such as prenatal inflammation, that introduce redox-immune-inflammatory alterations and risk for psychotic symptoms later in life. Nutraceuticals may offer useful adjunctive benefits. The aim of this study was to examine the therapeutic effects of Garcinia mangostana Linn (GML) and one of its active constituents, α-mangostin (AM), alone and as adjunctive treatment with haloperidol (HAL) on schizophrenia related bio-behavioral alterations in a maternal immune-activation (MIA) model. Sprague-Dawley dams were exposed to lipopolysaccharide (LPS) (n = 18) or vehicle (n = 3) on gestational days 15 and 16. Male offspring (n = 72) were treated from PND 52-66 with either vehicle, HAL (2 mg/kg), GML (50 mg/kg), HAL + GML, AM (20 mg/kg), or HAL + AM. Control dams and control offspring were treated with vehicle. In order to cover the mood-psychosis continuum, prepulse inhibition (PPI) of startle, open field test (locomotor activity), and the forced swim test (depressive-like behavior) were assessed on PND's 64-65, followed by assay of frontal-cortical lipid peroxidation and plasma pro-inflammatory cytokines, viz. interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). MIA-induced deficits in sensorimotor gating were reversed by HAL and HAL + GML, but not GML and AM alone. MIA-induced depressive-like behavior was reversed by AM and GML alone and both in combination with HAL, with the combinations more effective than HAL. MIA-induced cortical lipid peroxidation was reversed by HAL and AM, with elevated IL-6 levels restored by GML, AM, HAL, and HAL + GML. Elevated TNF-α was only reversed by GML and HAL + GML. Concluding, prenatal LPS-induced psychotic- and depressive-like bio-behavioral alterations in offspring are variably responsive to HAL, GML, and AM, with depressive (but not psychosis-like) manifestations responding to GML, AM, and combinations with HAL. AM may be a more effective antioxidant than GML in vivo, although this does not imply an improved therapeutic response, for which trials are required.
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    Minocycline for the treatment of mental health and neurological conditions: study protocol of a systematic review and meta-analysis
    Bortolasci, CC ; Marx, W ; Walker, AJ ; Hasebe, K ; Kavanagh, BE ; Morris, MJ ; Mohebbi, M ; Turner, A ; Gray, L ; Berk, L ; Walder, K ; Berk, M ; Dean, OM (BMJ PUBLISHING GROUP, 2020-03-01)
    INTRODUCTION: Due to the anti-inflammatory, antioxidant and anti-apoptotic properties of minocycline, clinical trials have evaluated the potential of this drug to treat several psychiatric and neurological disorders, including major depressive disorder, schizophrenia, bipolar disorder, stroke and amyotrophic lateral sclerosis. This protocol proposes a systematic review (and potential meta-analysis) that aims to identify and critically evaluate randomised controlled trials of minocycline for treating psychiatric and neurological disorders. METHODS AND ANALYSIS: PubMed, Embase, Cochrane Central Register of Controlled Clinical Trials, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be used to identify randomised controlled trials that used minocycline to treat psychiatric and neurological disorders. Double-blind, randomised, controlled, clinical trials of participants aged 18 years or older and written in English will be included in the review. Data will be extracted by two independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed and the Cochrane Collaboration's 'Risk of Bias' tool will be used to assess the risk of bias in all studies included in the systematic review. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to access the overall quality of the level of evidence of the studies. If sufficient evidence is identified, a meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. Heterogeneity of evidence will be evaluated using the I2 model. ETHICS AND DISSEMINATION: This systematic review will evaluate only published data; therefore, ethical approval is not required. The systematic review will be published in a peer-reviewed journal and presented at relevant research conferences. TRIAL REGISTRATION NUMBER: CRD42020153292.
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    Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin
    Berk, M ; Mohebbi, M ; Dean, OM ; Cotton, SM ; Chanen, AM ; Dodd, S ; Ratheesh, A ; Amminger, GP ; Phelan, M ; Weller, A ; Mackinnon, A ; Giorlando, F ; Baird, S ; Incerti, L ; Brodie, RE ; Ferguson, NO ; Rice, S ; Schafer, MR ; Mullen, E ; Hetrick, S ; Kerr, M ; Harrigan, SM ; Quinn, AL ; Mazza, C ; McGorry, P ; Davey, CG (BMC, 2020-01-17)
    BACKGROUND: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). METHODS: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (- 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (- 4.2, 95% CI (- 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. CONCLUSIONS: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.