Faculty Bibliography

Approaching the 30th anniversary of the discovery of resting state functional magnetic resonance imaging (rsfMRI) functional connectivity, we reflect on the impact of this neuroimaging breakthrough on the field of child and adolescent psychiatry. The study of intrinsic functional brain architecture that rsfMRI affords across a wide range of ages and abilities has yielded numerous key insights. For example, we now know that many neurodevelopmental conditions are associated with more widespread circuit alterations across multiple large-scale brain networks than previously suspected. The emergence of population neuroscience and effective data-sharing initiatives have made large rsfMRI datasets publicly available, providing sufficient power to begin to identify brain-based subtypes within heterogeneous clinical conditions. Nevertheless, several methodological and theoretical challenges must still be addressed to fulfill the promises of personalized child and adolescent psychiatry. In particular, incomplete understanding of the physiological mechanisms driving developmental changes in intrinsic functional connectivity remains an obstacle to further progress. Future directions include cross-species and multimodal neuroimaging investigations to illuminate such mechanisms. Data collection and harmonization efforts that span multiple countries and diverse cohorts are urgently needed. Finally, incorporating naturalistic fMRI paradigms such as movie watching should be a priority for future research efforts.

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.

PURPOSE/OBJECTIVE:Stronger Together is a peer mentoring model that seeks to address the severe lack of mental health and psychosocial support for patients with cancer in many low- and middle-income countries (LMICs). This article presents the results of the Stronger Together pilot study among patients with breast and gynecologic cancer in Viet Nam (VN). METHODS:Eligible participants comprised women age 25 years or older with a diagnosis of breast or gynecologic cancers and receiving treatment at four participating hospitals. Participants were asked whether they wanted to proceed with usual care or be matched with a trained and supervised peer mentor (a cancer survivor). Surveys were administered at baseline (0) and 2, 4, and 6 months and assessed depression, anxiety, stress, mental health and physical health components of quality of life (QOL), self-efficacy, and social support. We computed and compared 2-, 4-, and 6-month changes in scores from baseline and conducted difference-in-difference analyses to estimate the intervention effect at 6 months. RESULTS:The sample size included N = 186 participants. Mentees (n = 91) exhibited improvements in depression, anxiety, stress, and mental health QOL across all time points, whereas usual care participants (n = 95) experienced these improvements at later periods (4 and 6 months). Compared with usual care participants, mentees reported greater improvements in depression at 2 and 4 months, mental health QOL at all time points, and self-efficacy and social support at 4 and 6 months. Greater improvements in stress were also seen in the breast cancer subsample. CONCLUSION/CONCLUSIONS:Stronger Together is a promising model to improve mental health and psychosocial outcomes among patients with breast and gynecologic cancer in VN and can help fill gaps in cancer peer support interventions in many LMICs.

Research suggests that socioeconomic circumstances and stress predict memory skills in adults and older children, yet few studies have addressed this question in infancy. The current study used the visual-paired comparison paradigm to examine whether socioeconomic circumstances, maternal perceived stress, and/or maternal physiological stress, all measured prenatally, predict memory performance among 6-month-old infants. We found no significant associations between infant memory and any measure of socioeconomic circumstance or stress. Potential explanations for these null findings are discussed.

BACKGROUND:A growing body of literature links prenatal mood and substance use to children's cognitive and behavioral development. The relative contribution of these risk factors on children's executive function (EF) in the context of socioeconomic adversities needs further evaluation. To address this gap, we investigated the role of prenatal maternal anxiety and depression on childhood EF, specifically inhibitory control and working memory, within the context of socioeconomic adversities and prenatal substance use. We hypothesized that higher maternal mood symptoms, higher persistent prenatal drinking and smoking, and lower socioeconomic status would be associated with lower EF skills during early childhood. METHODS:We used data from 334 mother-child dyads followed prospectively through pregnancy and the offspring's childhood. Prenatal maternal depression and anxiety were assessed via standardized questionnaires. Prenatal alcohol and tobacco consumption were assessed via a timeline follow-back interview. The EF touch battery assessed child inhibitory control and working memory at 3-5 years of age (4.76 ± 0.58 years, 171 females). Separate linear regression models were used to estimate the association of prenatal tobacco, alcohol, anxiety, and depression exposure with our two components of child EF, inhibitory control and working memory, while adjusting for gestational age, sex, and age at assessment. The following variables were also included as covariates: maternal educational achievement, employment status, parity, and household crowding index. RESULTS:Children of mothers with high trait anxiety scores had reduced inhibitory control compared to children of mothers without trait anxiety or depression (β = -0.12, 95% CI:-0.22,-0.01). Children of mothers in the moderate to high continuous smoking group showed lower inhibitory control (β = - 0.19, 95% CI:-0.38,-0.01) compared to children of mothers in the none smoking group. Additionally, lower maternal education and higher household crowding were each associated with reduced inhibitory control. We found no significant association between prenatal maternal depression, anxiety, or socioeconomic factors with working memory. CONCLUSIONS:These results underscore the need for comprehensive context-specific intervention packages, including mental health support for women to promote healthy inhibitory control development in children.

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.

Neurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult-born neurons would prevent epilepsy. Adult-born neurons were selectively increased by deleting the pro-apoptotic gene Bax from Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally delete Bax in Nestin-CreER^T2

OBJECTIVE:Suicide and suicidal behaviour strongly contribute to overall male youth mortality. An understanding of worldwide data contextualises suicide and suicidal behaviour in young men within any given country. METHOD/METHODS:Members and colleagues of the World Federation of Societies of Biological Psychiatry's Task Force on Men's Mental Health review the relevant data from several regions of the world. The review identifies notable findings across regions of relevance to researchers, policymakers, and clinicians. RESULTS:Male suicide and suicidal behaviour in adolescence and emerging adulthood within North America, Latin America and the Caribbean, Europe, the Mediterranean and the Middle East, Continental Africa, South Asia, East Asia, China, and Oceania share similarities as well as significant points of divergence. CONCLUSIONS:International data provide an opportunity to obtain a superior understanding of suicide and suicidal behaviour amongst young men.

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 .