Faculty Bibliography

BACKGROUND:Placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder. METHODS:We searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms. RESULTS:= 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91-1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types. CONCLUSION/CONCLUSIONS:Placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.

OBJECTIVE:Attention-deficit/hyperactivity disorder (ADHD) is associated with lower birth weight, but also with obesity in childhood. Findings on the direction of this association are mixed. This study investigated the relationship between weight and ADHD from birth across development. METHOD/METHODS:We used data from the Millennium Cohort Study (MCS), collected at 7 time points between age 9 months and 17 years. ADHD diagnosis status and scores on the Strength and Difficulties Questionnaire (SDQ) were used to create an ADHD group and a control group. Random intercept cross-lagged panel models were conducted in female individuals (n = 4,051) and male individuals (n = 3,857) to examine bidirectional associations between body mass index (BMI) z scores and SDQ scores between ages 3 and 17 years. Analyses were adjusted for common risk factors for ADHD and obesity, such as sex assigned at birth, multiple births, and ADHD medication status. RESULTS:Children in the ADHD group were significantly lighter in weight at birth than the control group (t[5674] = 2.65, 95% CI = 0.02, 0.14, p = .008) and were significantly more likely to have obesity at age 5 years onward (odds ratio range = 1.57-2.46, relative risk range 0.98-2.29). Path analyses conducted separately for male and female individuals showed that higher ADHD symptoms in female individuals at ages 7, 11, and 14 years significantly predicted higher BMI z scores at ages 11, 14, and 17 years, respectively. In male individuals, this association was seen only between ages 11 and 14 years (β = 0.07; 95% CI = 0.04-0.10, p < .001). CONCLUSION/CONCLUSIONS:Results suggest that interventions for children with ADHD, and their parents, should begin as soon as possible, ideally prenatally. Developmental sex differences should be considered.

In the past decade, there have been substantial changes in diagnostic nomenclature. This study investigated sex differences in attention-deficit/hyperactivity disorder (ADHD) symptom severity based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV(TR), and DSM-5 criteria, separating rating scale and clinical interview data in children and adults with ADHD. PubMed, PsycINFO, and Scopus were searched for published studies (1996-2021) reporting severity of attention, and hyperactivity/impulsivity in males and females. We compared data: (1) across the entire lifespan aggregating rating scale and clinical interview data (51 studies), (2) drawing solely on rating scale data (18 studies), and (3) drawing solely on clinical interview data (33 studies). Fifty-two studies met inclusion criteria comparing data for females (n = 8423) and males (n = 9985) with ADHD across childhood and/or adulthood. In total, 15 meta-analyses were conducted. Pooled data across the lifespan aggregating both rating scale and clinical diagnostic interview data, showed males had significantly more severe hyperactivity/impulsivity symptoms than females. Rating scale data were similar; boys had significantly more severe hyperactivity/impulsivity than girls. In adulthood, men were rated to have significantly more severe inattention than women with no difference in the hyperactivity/impulsivity dimension. All significant differences were of small effect size. No significant sex differences in the severity of symptoms emerged for clinical interview data for children or adults, in contrast. Possible reasons for the discrepancy in findings between rating scales and clinical diagnostic interviews are discussed.

To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.

Suicide is a significant leading cause of death among young people, particularly those struggling with mental disorders. The present study utilised data from 230 young people (aged 16-18 years) undergoing a transitional care process from Child and Adolescent Mental Health Services to Adult Mental Health Services within the MILESTONE European project (2014-2019), a longitudinal cluster randomised controlled trial. The objectives of this study were to monitor temporal patterns of general health and social functioning over two years, to detect sex differences, and to identify factors associated with Suicidal Thoughts and Behaviours (STB) at the first and last time points. The results demonstrate a decrease in STB over the two-year follow-up period among all participants. Females exhibited a higher prevalence of STB across all time points, whereas males only exhibited STB at the nine-month follow-up. The most influential factors associated with STB were previous suicide attempts and mood disorders at baseline, and mood disorders and relational problems at the end of follow-up. These findings emphasise the importance of monitoring STB and informing young people undergoing a transitional care period about its key risk factors. Moreover, sex differences in STB suggest the need for different preventive strategies for males and females.

BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5% of children globally, with symptoms often persisting into adulthood. While pharmacological interventions are commonly employed for management, understanding the optimal dosing for efficacy and tolerability remains crucial. This study aims to conduct a dose-response network meta-analysis to estimate the efficacy of pharmacological treatments across different doses, aiming to inform clinical decision-making and improve treatment outcomes. METHODS:This updated systematic review will include randomized controlled trials evaluating ADHD medication efficacy in children, adolescents, and adults. An updated search from a 2018 NMA will be conducted across multiple electronic databases with no language restrictions, using specific eligibility criteria focused on randomized controlled trials. The primary outcome will assess the severity of ADHD core symptoms, while secondary outcomes will consider treatment tolerability. A dose-response Bayesian hierarchical model will be used to estimate dose-response curves for each medication, identifying optimal dosing strategies. DISCUSSION/CONCLUSIONS:With this dose-response network meta-analysis, we aim to better understand the dose-response relationship of pharmacological treatment in ADHD, which could help clinician to the identification of optimal doses. SYSTEMATIC REVIEW REGISTRATION/BACKGROUND:OSF https://doi.org/10.17605/OSF.IO/3MY4A .