Psychiatry - Research Publications
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ItemMixed Methods Thematic Analysis of a Randomised Controlled Trial of Adjunctive Mitochondrial Agents for Bipolar Depression(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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ItemNo Preview AvailableEffects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial(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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ItemEffect of Glucocorticoid and 11β-Hydroxysteroid-Dehydrogenase Type 1 (11β-HSD1) in Neurological and Psychiatric Disorders(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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ItemVariations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder(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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ItemThe Role of Mitochondria in Mood Disorders: From Physiology to Pathophysiology and to Treatment(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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ItemEditorial: Placebo and Nocebo Effects in Psychiatry and Beyond(FRONTIERS MEDIA SA, 2020-08-07)
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ItemYouth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin(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.
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ItemAge as a predictor of quit attempts and quit success in smoking cessation: findings from the International Tobacco Control Four-Country survey (2002-14)(WILEY, 2021-09)BACKGROUND AND AIMS: Past research has found that young smokers are more likely to make quit attempts; however, there are conflicting findings regarding age and quit success. This study examined the degree to which smoker age is related to making quit attempts and quit success. DESIGN: Ten waves of the International Tobacco Control Policy Cohort survey (ITC-4C) collected between 2002 and 2014, with nine wave-to-wave transitions with predictors at the first wave predicting quit attempts and success by the next wave. SETTING: Canada, the United States, the United Kingdom and Australia. PARTICIPANTS: Data from 15 874 smokers categorized into four age groups at baseline (18-24, 25-39, 40-54 and 55+ years). MEASUREMENTS: Age, quit attempts and success (defined as ≥ 30 days abstinence confirmed, if possible, on a third wave for recent attempts). FINDINGS: Older smokers were more likely to smoke daily (χ2 = 1557.86, r = 0.136, P < 0.001) than younger smokers. Daily smokers were less likely to report quit attempts (38.1 versus 58.2%) and to achieve 30 days of abstinence (22.9 versus 34.3%) than non-daily smokers. Older daily smokers were less likely to make quit attempts [0.61, confidence interval (CI) = 0.54-0.70, P < 0.001], even after controlling for indicators of nicotine dependence, country, sex, education, income, relationship status and household composition, than younger smokers. Younger smokers (< 25) were more likely to succeed for at least 30 days of abstinence, but only when compared with those aged 40-54 (OR = 0.83, 95% CI = 0.68-0.99). However, when controlling for heaviness of smoking the age effect disappeared. Significant interactions with age were found between age and intention when predicting quit attempts, and age and heaviness of smoking when predicting quit success. CONCLUSIONS: An international cohort study indicates that young smokers are more likely to attempt to quit and appear to have similar levels of success in abstaining from smoking compared with older smokers when controlling for dependence. Quit success in all ages is most predicted by lower levels of nicotine dependence.