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Objective: Harmonized tools are essential for reliable data sharing and accurate identification of relevant factors in mental health research. The primary objective of this study was to create a harmonized questionnaire to collect demographic, clinical and behavioral data in diverse clinical trials in adult psychiatry. Methods: We conducted a literature review and examined 24 questionnaires used in previously published randomized controlled trials in psychiatry, identifying a total of 27 domains previously explored. Using a Delphi-method process, a task force team comprising experts in psychiatry, epidemiology and statistics selected 15 essential domains for inclusion in the final questionnaire. Results: The final selection resulted in a concise set of 22 questions. These questions cover factors such as age, sex, gender, ancestry, education, living arrangement, employment status, home location, relationship status, and history of medical and mental illness. Behavioral factors like physical activity, diet, smoking, alcohol and illicit drug use were also included, along with one question addressing family history of mental illness. Income was excluded due to high confounding and redundancy, while language was included as a measure of migration status. Conclusion: The recommendation and adoption of this harmonized tool for the assessment of demographic, clinical and behavioral data in mental health research can enhance data consistency and enable comparability across clinical trials. [ABSTRACT FROM AUTHOR]

Background: Traditional treatment for the behavioural symptoms in autism spectrum disorder (ASD) remains unsatisfactory. There is an urgent need for new, biologically relevant therapies that target both the core and comorbid symptoms that children may experience. This article builds on research previously published by the authors. Method: We report a mixed-methods analysis from a 24-week double-blind randomised controlled trial of adjunctive "N"-acetylcysteine (NAC) for the treatment of behavioural symptoms in ASD. Ninety-eight children between the ages of 3 and 9 years, diagnosed with ASD, participated in the study. Outcome measures included parents' assessment reports (obtained before, during, and after the trial), clinicians' observations, and the researchers' detailed case notes. Thematic analysis of textual data (n = 85) was carried out, followed by an evaluation of differences in the frequency with which changes in behaviour were qualitatively reported. Results: Compared with placebo, the parents of the group that received NAC reported improved calmness, decreased aggression and agitation, and greater improvements in verbal communication. Conclusions: These results support the usefulness of NAC for treating potentially disruptive behaviour (e.g., aggression and hyperactivity) in children with ASD and provide a novel finding: potentially improved verbal communication following NAC treatment. This paper supports the utility of a mixed-methods analysis for detecting latent signals in clinical trials.

Patients with asthma experience elevated rates of mental illness. However, the molecular links underlying such lung–brain crosstalk remain ambiguous. Hypothalamic dysfunction is observed in many psychiatric disorders, particularly those with an inflammatory component due to many hypothalamic regions being unprotected by the blood–brain barrier. To gain a better insight into such neuropsychiatric sequelae, this study investigated gene expression differences in the hypothalamus following lung inflammation (asthma) induction in mice, using RNA transcriptome profiling. BALB/c mice were challenged with either bacterial lipopolysaccharide (LPS, E. coli) or ovalbumin (OVA) allergens or saline control (n = 7 per group), and lung inflammation was confirmed via histological examination of postmortem lung tissue. The majority of the hypothalamus was micro-dissected, and total RNA was extracted for sequencing. Differential expression analysis identified 31 statistically significant single genes (false discovery rate FDR5%) altered in expression following LPS exposure compared to controls; however, none were significantly changed following OVA treatment, suggesting a milder hypothalamic response. When gene sets were examined, 48 were upregulated and 8 were downregulated in both asthma groups relative to controls. REACTOME enrichment analysis suggests these gene sets are involved in signal transduction metabolism, immune response and neuroplasticity. Interestingly, we identified five altered gene sets directly associated with neurotransmitter signaling. Intriguingly, many of these altered gene sets can influence mental health and or/neuroinflammation in humans. These findings help characterize the links between asthma-induced lung inflammation and the brain and may assist in identifying relevant pathways and therapeutic targets for future intervention. [ABSTRACT FROM AUTHOR]

N-Acetylcysteine (NAC) is a synthetic derivate of the endogenous amino acid L-cysteine (Figure 1) and a precursor of glutathione. It is known for its role in modulating oxidative stress and [...]

Objectives: Many people who are diagnosed with bipolar disorder also have comorbid personality disorder. Few studies have explored how personality disorder may influence pharmacological treatment outcomes. The aim of this study was to conduct a secondary analysis of data from a clinical trial of adjunctive nutraceutical treatments for bipolar depression, to determine whether maladaptive personality traits influence treatment outcomes. Methods: Scores on the Standardised Assessment of Personality – Abbreviated Scale screener were used to classify participants as having bipolar disorder with (n = 119) and without (n = 29) above threshold personality disorder symptoms (personality disorder). Outcome measures included: The Montgomery Åsberg Depression Rating Scale, Clinical Global Impressions and Improvement Severity Scales, Patient Global Impressions–Improvement scale, Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, Social and Occupational Functioning Assessment Scale and Quality of Life and Enjoyment Scale (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form). Generalised estimated equations examined the two-way interactions of personality disorder by time or treatment and investigated personality disorder as a non-specified predictor of outcomes. Results: Over time, the Patient Global Impressions–Improvement scores were significantly higher in those in the personality disorder group. No other significant differences in the two-way interactions of personality disorder by treatment group or personality disorder by time were found. Personality disorder was a significant but non-specific predictor of poorer outcomes on the Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, regardless of time or treatment group. Conclusions: This study highlights the potential impact of maladaptive personality traits on treatment outcomes and suggests that the presence of comorbid personality disorder may confer additional burden and compromise treatment outcomes. This warrants further investigation as does the corroboration of these exploratory findings. This is important because understanding the impact of comorbid personality disorder on bipolar disorder may enable the development of effective psychological and pharmacotherapeutic options for personalised treatments. [ABSTRACT FROM AUTHOR]

Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to repurpose a drug for the treatment of bipolar depression. Methods: A gene expression signature representing the overall transcriptomic effects of a cocktail of drugs widely prescribed to treat bipolar disorder was generated using human neuronal‐like (NT2‐N) cells. A compound library of 960 approved, off‐patent drugs were then screened to identify those drugs that affect transcription most similar to the effects of the bipolar depression drug cocktail. For mechanistic studies, peripheral blood mononuclear cells were obtained from a healthy subject and reprogrammed into induced pluripotent stem cells, which were then differentiated into co‐cultured neurons and astrocytes. Efficacy studies were conducted in two animal models of depressive‐like behaviours (Flinders Sensitive Line rats and social isolation with chronic restraint stress rats). Results: The screen identified trimetazidine as a potential drug for repurposing. Trimetazidine alters metabolic processes to increase ATP production, which is thought to be deficient in bipolar depression. We showed that trimetazidine increased mitochondrial respiration in cultured human neuronal‐like cells. Transcriptomic analysis in induced pluripotent stem cell‐derived neuron/astrocyte co‐cultures suggested additional mechanisms of action via the focal adhesion and MAPK signalling pathways. In two different rodent models of depressive‐like behaviours, trimetazidine exhibited antidepressant‐like activity with reduced anhedonia and reduced immobility in the forced swim test. Conclusion: Collectively our data support the repurposing of trimetazidine for the treatment of bipolar depression. [ABSTRACT FROM AUTHOR]