Minerva Elements Records

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    Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?
    Russell, SE ; Wrobel, AL ; Ashton, MM ; Turner, A ; Mohebbi, M ; Berk, M ; Cotton, S ; Dodd, S ; Ng, CH ; Malhi, GS ; Dean, OM (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2023-08)
    OBJECTIVE: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. METHODS: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (+4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. RESULTS: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. CONCLUSION: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
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    Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management
    Berk, M ; Kohler-Forsberg, O ; Turner, M ; Penninx, BWJH ; Wrobel, A ; Firth, J ; Loughman, A ; Reavley, NJ ; Mcgrath, JJ ; Momen, NC ; Plana-Ripoll, O ; O'Neil, A ; Siskind, D ; Williams, LJ ; Carvalho, AF ; Schmaal, L ; Walker, AJ ; Dean, O ; Walder, K ; Berk, L ; Dodd, S ; Yung, AR ; Marx, W (WILEY, 2023-10)
    Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.
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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)
    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. 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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    Effects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial
    Berk, M ; Agustini, B ; Woods, RL ; Nelson, MR ; Shah, RC ; Reid, CM ; Storey, E ; Fitzgerald, SM ; Lockery, JE ; Wolfe, R ; Mohebbi, M ; Dodd, S ; Murray, AM ; Stocks, N ; Fitzgerald, PB ; Mazza, C ; McNeil, JJ (SPRINGERNATURE, 2021-09)
    Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1879 were depressed at baseline. Participants were given 100 mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; χ2 (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (-0.7; 95% CI -1.4 to -0.1; χ2 (1) = 4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms.
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    Effect of Glucocorticoid and 11β-Hydroxysteroid-Dehydrogenase Type 1 (11β-HSD1) in Neurological and Psychiatric Disorders
    Dodd, S ; Skvarc, DR ; Dean, OM ; Anderson, A ; Kotowicz, M ; Berk, M (OXFORD UNIV PRESS, 2022-05-27)
    11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity is implicated as a moderator of the progression of multiple diseases and disorders in medicine and is actively subject to investigation as a therapeutic target. Here we summarize the mechanisms of the enzyme and detail the novel agents under investigation. Such agents modulate peripheral cortisol and cortisone levels in hypertension, type 2 diabetes, metabolic disorders, and Alzheimer's disease models, but there is mixed evidence for transduction into symptom management. There is inchoate evidence that 11β-HSD1 modulators may be useful pharmacotherapies for clinical improvement in psychiatry and neurology; however, more research is required.
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    Impact of irritability: a 2-year observational study of outpatients with bipolar I or schizoaffective disorder
    Berk, L ; Hallam, KT ; Venugopal, K ; Lewis, AJ ; Austin, DW ; Kulkarni, J ; Dodd, S ; de Castella, A ; Fitzgerald, PB ; Berk, M (WILEY, 2017-05)
    OBJECTIVES: Many people experience irritability when manic, hypomanic, or depressed, yet its impact on illness severity and quality of life in bipolar and schizoaffective disorders is poorly understood. This study aimed to examine the relationship between irritability and symptom burden, functioning, quality of life, social support, suicidality, and overall illness severity in a naturalistic cohort of people with bipolar I or schizoaffective disorder. METHODS: We used data from 239 adult outpatients with bipolar I or schizoaffective disorder in the Bipolar Comprehensive Outcomes Study (BCOS) - a non-interventional observational study with a 2-year follow-up period. Baseline demographic and clinical characteristics of participants with and without irritability were compared. A mixed-model repeated measures analysis was conducted to examine the longitudinal effect of irritability on clinical and quality-of-life variables over follow-up using significant baseline variables. RESULTS: At baseline, 54% of participants were irritable. Baseline irritability was associated with illness severity, mania, depression, psychotic symptoms, suicidality, poor functioning, and quality of life, but not diagnosis (schizoaffective/bipolar disorder). Participants with irritability were less likely to have a partner and perceived less adequate social support. On average, over follow-up, those with irritability reported more symptoms, functional impairment, and suicidality. Furthermore, the effects of irritability could not be fully explained by illness severity. CONCLUSIONS: Irritability was associated with more negative symptomatic, functional, and quality-of-life outcomes and suicidality. The identification, monitoring, and targeted treatment of irritability may be worth considering, to enhance health and wellbeing outcomes for adults with bipolar and schizoaffective disorders.
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    Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder
    Bauer, M ; Glenn, T ; Achtyes, ED ; Alda, M ; Agaoglu, E ; Altinbas, K ; Andreassen, OA ; Angelopoulos, E ; Ardau, R ; Vares, EA ; Aydin, M ; Ayhan, Y ; Baethge, C ; Bauer, R ; Baune, BT ; Balaban, C ; Becerra-Palars, C ; Behere, AP ; Behere, PB ; Belete, H ; Belete, T ; Belizario, GO ; Bellivier, F ; Belmaker, RH ; Benedetti, F ; Berk, M ; Bersudsky, Y ; Bicakci, S ; Birabwa-Oketcho, H ; Bjella, TD ; Brady, C ; Cabrera, J ; Cappucciati, M ; Castro, AMP ; Chen, W-L ; Cheung, EYW ; Chiesa, S ; Crowe, M ; Cuomo, A ; Dallaspezia, S ; Del Zompo, M ; Desai, P ; Dodd, S ; Donix, M ; Etain, B ; Fagiolini, A ; Fellendorf, FT ; Ferensztajn-Rochowiak, E ; Fiedorowicz, JG ; Fountoulakis, KN ; Frye, MA ; Geoffroy, PA ; Gonzalez-Pinto, A ; Gottlieb, JF ; Grof, P ; Haarman, BCM ; Harima, H ; Hasse-Sousa, M ; Henry, C ; Hoffding, L ; Houenou, J ; Imbesi, M ; Isometsa, ET ; Ivkovic, M ; Janno, S ; Johnsen, S ; Kapczinski, F ; Karakatsoulis, GN ; Kardell, M ; Kessing, LV ; Kim, SJ ; Koenig, B ; Kot, TL ; Koval, M ; Kunz, M ; Lafer, B ; Landen, M ; Larsen, ER ; Lenger, M ; Lewitzka, U ; Licht, RW ; Lopez-Jaramillo, C ; MacKenzie, A ; Madsen, HO ; Madsen, SAKA ; Mahadevan, J ; Mahardika, A ; Manchia, M ; Marsh, W ; Martinez-Cengotitabengoa, M ; Martiny, K ; Mashima, Y ; McLoughlin, DM ; Meesters, Y ; Melle, I ; Meza-Urzua, F ; Ming, MY ; Monteith, S ; Moorthy, M ; Morken, G ; Mosca, E ; Mozzhegorov, AA ; Munoz, R ; Mythri, S ; Nacef, F ; Nadella, RK ; Nakanotani, T ; Nielsen, RE ; O'Donovan, C ; Omrani, A ; Osher, Y ; Ouali, U ; Pantovic-Stefanovic, M ; Pariwatcharakul, P ; Petite, J ; Pfennig, A ; Ruiz, YP ; Pilhatsch, M ; Pinna, M ; Pompili, M ; Porter, R ; Quiroz, D ; Rabelo-da-Ponte, FD ; Ramesar, R ; Rasgon, N ; Ratta-Apha, W ; Ratzenhofer, M ; Redahan, M ; Reddy, MS ; Reif, A ; Reininghaus, EZ ; Richards, JG ; Ritter, P ; Rybakowski, JK ; Sathyaputri, L ; Scippa, AM ; Simhandl, C ; Severus, E ; Smith, D ; Smith, J ; Stackhouse, PW ; Stein, DJ ; Stilwell, K ; Strejilevich, S ; Su, K-P ; Subramaniam, M ; Sulaiman, AH ; Suominen, K ; Tanra, AJ ; Tatebayashi, Y ; Teh, WL ; Tondo, L ; Torrent, C ; Tuinstra, D ; Uchida, T ; Vaaler, AE ; Veeh, J ; Vieta, E ; Viswanath, B ; Yoldi-Negrete, M ; Yalcinkaya, OK ; Young, AH ; Zgueb, Y ; Whybrow, PC (SPRINGER, 2021-09-01)
    BACKGROUND: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. METHODS: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). RESULTS: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. CONCLUSION: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
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    The Role of Mitochondria in Mood Disorders: From Physiology to Pathophysiology and to Treatment
    Gimenez-Palomo, A ; Dodd, S ; Anmella, G ; Carvalho, AF ; Scaini, G ; Quevedo, J ; Pacchiarotti, I ; Vieta, E ; Berk, M (FRONTIERS MEDIA SA, 2021-07-06)
    Mitochondria are cellular organelles involved in several biological processes, especially in energy production. Several studies have found a relationship between mitochondrial dysfunction and mood disorders, such as major depressive disorder and bipolar disorder. Impairments in energy production are found in these disorders together with higher levels of oxidative stress. Recently, many agents capable of enhancing antioxidant defenses or mitochondrial functioning have been studied for the treatment of mood disorders as adjuvant therapy to current pharmacological treatments. A better knowledge of mitochondrial physiology and pathophysiology might allow the identification of new therapeutic targets and the development and study of novel effective therapies to treat these specific mitochondrial impairments. This could be especially beneficial for treatment-resistant patients. In this article, we provide a focused narrative review of the currently available evidence supporting the involvement of mitochondrial dysfunction in mood disorders, the effects of current therapies on mitochondrial functions, and novel targeted therapies acting on mitochondrial pathways that might be useful for the treatment of mood disorders.
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    The Effect of Adjunctive Mangosteen Pericarp on Cognition in People With Schizophrenia: Secondary Analysis of a Randomized Controlled Trial
    Marx, W ; Skvarc, DR ; Mohebbi, M ; Walker, AJ ; Meehan, A ; Turner, A ; Baker, A ; Dodd, S ; Cotton, SM ; Scott, JG ; Kavanagh, BE ; Ashton, MM ; Brown, E ; McGrath, JJ ; Berk, M ; Dean, OM (FRONTIERS MEDIA SA, 2021-06-15)
    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.
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    Putative neuroprotective pharmacotherapies to target the staged progression of mental illness
    Robertson, OD ; Coronado, NG ; Sethi, R ; Berk, M ; Dodd, S (WILEY, 2019-10)
    AIM: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential. METHOD: Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin. RESULTS: Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants; other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands; and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen. CONCLUSIONS: Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.