Psychiatry - Research Publications

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    Associations of Cardiovascular Agents and Metformin with Depression Symptoms: A Cross-Sectional Analysis from the HUNT Study, Norway.
    Bojanić, I ; Bjerkeset, O ; Williams, LJ ; Berk, M ; Sund, ER ; Sletvold, H (Springer Science and Business Media LLC, 2022-09)
    BACKGROUND: Cardiovascular agents, including angiotensin-converting enzyme inhibitors, angiotensin II receptor inhibitors, acetylsalicylic acid, statins, and metformin, have demonstrated benefits for depression. However, there is scant evaluation of these drugs' antidepressant properties in large population settings. OBJECTIVE: This study aimed to examine cross-sectional associations between depression symptoms and the use of cardiovascular agents and metformin in populations with cardiovascular diseases or diabetes mellitus. METHODS: Participants in the Trøndelag Health Study 2006-08 (HUNT3, n = 40,516) and 2017-19 (HUNT4, n = 42,103) were included and data on their drug use from 2006 to 2019 was retrieved from the Norwegian Prescription Database. The outcome was self-reported depression symptoms defined by the Hospital Anxiety and Depression Scale. Associations between cardiovascular agents or metformin use and self-reported depression were analyzed by multi-level logistic regression in sex-stratified samples. RESULTS: Among men with cardiovascular diseases, use of acetylsalicylic acid was associated with reduced depression symptoms compared with acetylsalicylic acid non-users (reference) in HUNT3 and HUNT4 [risk ratio = 0.76; 95% confidence interval 0.59-0.94, risk ratio = 0.67; 95% CI 0.52-0.82, respectively]. Similarly, male statin users had a lower likelihood of reporting depression than statin non-users in HUNT3 (risk ratio = 0.70; 95% confidence interval 0.54-0.86) and HUNT4 (risk ratio = 0.67; 95% confidence interval 0.51-0.84). Associations between statins or acetylsalicylic acid use and reduced depression symptoms were detected in women with cardiovascular diseases in HUNT4. We found no statistical support for associations between other cardiovascular agents or metformin use and a reduced or increased depression symptom risk. CONCLUSIONS: Results suggest negative associations between acetylsalicylic acid or statin use and depression symptoms. However, longitudinal cohort studies and randomized controlled trials are required to confirm the antidepressant effects of these drugs.
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    Correction: A shared framework for the common mental disorders and Non-Communicable Disease: key considerations for disease prevention and control.
    O'Neil, A ; Jacka, FN ; Quirk, SE ; Cocker, F ; Taylor, CB ; Oldenburg, B ; Berk, M (Springer Science and Business Media LLC, 2022-05-27)
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    Prediction of disability-free survival in healthy older people.
    Neumann, JT ; Thao, LTP ; Murray, AM ; Callander, E ; Carr, PR ; Nelson, MR ; Wolfe, R ; Woods, RL ; Reid, CM ; Shah, RC ; Newman, AB ; Williamson, JD ; Tonkin, AM ; McNeil, JJ ; ASPREE investigators, (Springer Science and Business Media LLC, 2022-06)
    Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583).
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    Effects of Psychotropic Drugs on Ribosomal Genes and Protein Synthesis
    Liu, ZSJ ; Truong, TTT ; Bortolasci, CC ; Spolding, B ; Panizzutti, B ; Swinton, C ; Kim, JH ; Kidnapillai, S ; Richardson, MF ; Gray, L ; Dean, OM ; McGee, SL ; Berk, M ; Walder, K (MDPI, 2022-07-01)
    Altered protein synthesis has been implicated in the pathophysiology of several neuropsychiatric disorders, particularly schizophrenia. Ribosomes are the machinery responsible for protein synthesis. However, there remains little information on whether current psychotropic drugs affect ribosomes and contribute to their therapeutic effects. We treated human neuronal-like (NT2-N) cells with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM) or vehicle control for 24 h. Transcriptomic and gene set enrichment analysis (GSEA) identified that the ribosomal pathway was altered by these drugs. We found that three of the eight drugs tested significantly decreased ribosomal gene expression, whilst one increased it. Most changes were observed in the components of cytosolic ribosomes and not mitochondrial ribosomes. Protein synthesis assays revealed that aripiprazole, clozapine and lithium all decreased protein synthesis. Several currently prescribed psychotropic drugs seem to impact ribosomal gene expression and protein synthesis. This suggests the possibility of using protein synthesis inhibitors as novel therapeutic agents for neuropsychiatric disorders.
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    Integrative Analyses of Transcriptomes to Explore Common Molecular Effects of Antipsychotic Drugs
    Truong, TTT ; Bortolasci, CC ; Kidnapillai, S ; Spolding, B ; Panizzutti, B ; Liu, ZSJ ; Kim, JH ; Dean, OM ; Richardson, MF ; Berk, M ; Walder, K (MDPI, 2022-07-01)
    There is little understanding of the underlying molecular mechanism(s) involved in the clinical efficacy of antipsychotics for schizophrenia. This study integrated schizophrenia-associated transcriptional perturbations with antipsychotic-induced gene expression profiles to detect potentially relevant therapeutic targets shared by multiple antipsychotics. Human neuronal-like cells (NT2-N) were treated for 24 h with one of the following antipsychotic drugs: amisulpride, aripiprazole, clozapine, risperidone, or vehicle controls. Drug-induced gene expression patterns were compared to schizophrenia-associated transcriptional data in post-mortem brain tissues. Genes regulated by each of four antipsychotic drugs in the reverse direction to schizophrenia were identified as potential therapeutic-relevant genes. A total of 886 genes were reversely expressed between at least one drug treatment (versus vehicle) and schizophrenia (versus healthy control), in which 218 genes were commonly regulated by all four antipsychotic drugs. The most enriched biological pathways include Wnt signaling and action potential regulation. The protein-protein interaction (PPI) networks found two main clusters having schizophrenia expression quantitative trait loci (eQTL) genes such as PDCD10, ANK2, and AKT3, suggesting further investigation on these genes as potential novel treatment targets.
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    Counting on U training to enhance trusting relationships and mental health literacy among business advisors: protocol for a randomised controlled trial
    Saxon, L ; Bromfield, S ; Leow-Taylor, SH ; Vega, CE ; Berk, M ; LaMontagne, AD ; Martin, AJ ; Mohebbi, M ; Nielsen, K ; Reavley, NJ ; Walker, A ; Conway, A ; de Silva, A ; Memish, K ; Rossetto, A ; Tanewski, G ; Noblet, A (BMC, 2022-06-15)
    BACKGROUND: Financial distress is thought to be a key reason why small-medium enterprise (SME) owners experience higher levels of mental health conditions compared with the broader population. Business advisors who form trusting, high-quality relationships with their SME clients, are therefore well placed to: (1) help prevent/reduce key sources of financial distress, (2) better understand the business and personal needs of their clients and, (3) recognise the signs and symptoms of mental health conditions and encourage help-seeking where appropriate. The aim of this study is to compare the effectiveness of relationship building training (RBT) combined with mental health first aid (MHFA) training for business advisors with MHFA alone, on the financial and mental health of their SME-owner clients. METHODS: This is a single blind, two-arm randomised controlled trial. Participants will be business advisors who provide information, guidance and/or assistance to SME owner clients and are in contact with them at least 3 times a year. The business advisors will invite their SME-owner clients to complete 3 online surveys at baseline, 6- and 12-months. Business advisors will be randomised to one of two conditions, using a 1:1 allocation ratio: (1) MHFA with RBT; or (2) MHFA alone, and complete 3 online surveys at baseline, 2- and 6-months. Primary outcomes will be measured in the business advisors and consist of the quality of the relationship, stigmatizing attitude, confidence to offer mental health first aid, quality of life and provision of mental health first aid. Secondary outcomes will be measured in the SME owners and includes trust in their business advisors, the quality of this relationship, financial wellbeing, financial distress, psychological distress, help-seeking behaviour, and quality of life. To complement the quantitative data, we will include a qualitative process evaluation to examine what contextual factors impacted the reach, effectiveness, adoption, implementation, and maintenance of the training. DISCUSSION: As there is evidence for the connections between client trust, quality of relationship and financial and mental wellbeing, we hypothesise that the combined RBT and MHFA training will lead to greater improvements in these outcomes in SME owners compared with MHFA alone. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04982094 . Retrospectively registered 29/07/2021. The study started in February 2021 and the recruitment is ongoing.
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    Investing in Late-Life Brain Capital.
    Dawson, WD ; Smith, E ; Booi, L ; Mosse, M ; Lavretsky, H ; Reynolds, CF ; Cummings, J ; Brannally, P ; Hynes, W ; Lenze, EJ ; Manes, F ; Ayadi, R ; Frank, L ; Chapman, SB ; Robertson, IH ; Rubenstein, L ; Jraissati, J ; Ibáñez, A ; Fillit, H ; Jeste, DV ; Rao, A ; Berk, M ; Storch, EA ; Santuccione Chadha, A ; Eyre, HA ; Albert, SM (Oxford University Press (OUP), 2022)
    Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused on building late-life Brain Capital.
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    Mixed Methods Thematic Analysis of a Randomised Controlled Trial of Adjunctive Mitochondrial Agents for Bipolar Depression
    Russell, SE ; Wrobel, AL ; Dean, OM ; Berk, M ; Dodd, S ; Ng, CH ; Malhi, GS ; Cotton, SM ; Sarris, J ; Turner, A (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2022-05-01)
    Objective: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant's experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants' experience of a trial testing N -acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression. Methods: Case: report forms from a randomised controlled trial (RCT) of BD depression (n = 148) were analysed using a pragmatic adaption of grounded theory and thematic analysis. Results: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm. Conclusion: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasises the value of mixed-methods research in capturing participants' experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.
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    Trajectories of depressive symptoms in older adults and associated health outcomes
    Agustini, B ; Lotfaliany, M ; Mohebbi, M ; Woods, RL ; McNeil, JJ ; Nelson, MR ; Shah, RC ; Murray, AM ; Reid, CM ; Tonkin, A ; Ryan, J ; Williams, LJ ; Forbes, MP ; Berk, M (Springer Science and Business Media LLC, 2022-04-01)