Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:) is a nonstimulant medication that has been approved by the United States Food and Drug Administration (FDA) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children (> 6 years old) and adults. This phase 3 open-label extension to a pivotal phase 3, double-blind trial evaluated the long-term safety and continued efficacy of viloxazine ER in adults with ADHD. METHODS:This was a multicenter, flexible-dose, open-label extension to a phase III, double-blind, placebo-controlled trial (NCT04016779). Viloxazine ER was initiated at 200 mg/day and adjusted (between 200 and 600 mg/day) to achieve optimal efficacy and tolerability. Trial enrollment was halted temporarily (24 March 2020 to 23 July 2020) due to the coronavirus disease 2019 (COVID-19) pandemic. Participants completing double-blind treatment during that time were offered delayed enrollment upon trial requalification. Safety outcomes were the primary objectives. Secondary objectives were efficacy outcomes, including the ADHD Investigator Symptom Rating Scale (AISRS), and were assessed relative to double-blind baseline (or trial re-entry baseline for those whose enrollment was delayed by the COVID-19 pandemic). RESULTS:Overall, 159 participants (133 immediate and 26 delayed rollover) received viloxazine ER, with a mean exposure of 265 ± 254.9 days. Adverse events (AEs) included (> 10% incidence) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). AEs led to discontinuation for 17.6% of participants [most commonly insomnia (2.5%), nausea (2.5%), and fatigue (1.9%)]. AISRS total score [baseline mean ± standard deviation (SD): 37.9 ± 6.3] improved by the first follow-up visit (-11.4 ± 9.5; week 2) with continued improvement at subsequent visits (last on-study visit: -18.2 ± 11.54). Similar patterns of improvement were seen for other measures of efficacy, including quality of life and executive function. Following initial dose optimization, most participants (73%) used viloxazine ER doses ≥ 400 mg/day, with 36% using doses of 600 mg/day. CONCLUSIONS:Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment. CLINICAL TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov Identifier: NCT04143217.

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.

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

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.

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 .

BACKGROUND:Disordered eating in early adolescence impacts development, with long-term health implications. Minoritised adolescents might be at higher risk of disordered eating due to minority stress, but most research has focused on White, heterosexual, cisgender individuals; less is known about disordered eating among minoritised adolescents. We examined sexual, gender, racial, and ethnic identities in relation to disordered eating in early adolescence. METHOD/METHODS:Using 2-year follow-up data from adolescents ages 10-14 in the Adolescent Brain Cognitive Development Study (N = 9385), we examined associations between sexual, gender, racial, and ethnic identities and past-2 week disordered eating (preoccupation with weight, weight control behaviors, and binge eating). RESULTS:Compared to heterosexual peers, gay/bisexual adolescents had higher odds of all three outcomes (AOR 1.90-3.32); those "questioning" their sexual identity had higher odds of preoccupation with weight (AOR 1.82) and binge eating (AOR 2.53). Compared to cisgender adolescents, transgender adolescents had higher odds of binge eating (AOR 2.62); those "questioning" their gender identity had higher odds of preoccupation with weight (AOR 2.45). Adolescents whose racial identity was categorised as "Another" had higher odds of preoccupation with weight (AOR 1.46) and weight control behaviors (AOR 1.58) compared to White adolescents. Finally, Hispanic adolescents had higher odds of all disordered eating outcomes than non-Hispanic adolescents (AOR 1.25-1.59). DISCUSSION/CONCLUSIONS:This study is among the first to reveal disparities in disordered eating among minoritised early adolescents. Further examination of these disparities can inform future interventions. Healthcare providers are encouraged to screen for disordered eating, recognising that minoritised early adolescents may be at risk.

BACKGROUND:Benzodiazepines are frequently prescribed drugs; however, their prolonged use can lead to tolerance, dependence, and other adverse effects. Despite these risks, long-term use remains common, presenting a public health concern. This study aims to explore the beliefs and opinions held by the public regarding benzodiazepines, as understanding these perspectives may provide insights into their usage patterns. METHODS:We collected public tweets published in English between January 1, 2019, and October 31, 2020, that mentioned benzodiazepines. The content of each tweet and the characteristics of the users were analyzed using a mixed-method approach, including manual analysis and semi-supervised machine learning. RESULTS:Over half of the Twitter users highlighted the efficacy of benzodiazepines, with minimal discussion of their side effects. The most active participants in these conversations were patients and their families, with health professionals and institutions being notably absent. Additionally, the drugs most frequently mentioned corresponded with those most commonly prescribed by healthcare professionals. CONCLUSIONS:Social media platforms offer valuable insights into users' experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects. This analysis underscores the need to educate physicians, patients, and their families about the potential risks associated with benzodiazepine use and to promote clinical guidelines that support the proper management of these medications. CLINICAL TRIAL NUMBER/BACKGROUND:Not applicable.

OBJECTIVE:Because understanding barriers to universal suicide risk screening in pediatric emergency departments (PEDs) may improve both identification and management of suicidal behaviors and ideation, this study assessed barriers to a quality improvement initiative examining the use of a novel computerized adaptive test (CAT), the Kiddie-CAT, in 2 PEDs. METHODS:Research assistants (RAs) trained in Rapid Assessment Procedures-Informed Clinical Ethnography methods documented barriers related to the environment, individuals, and workflow as encountered during screening shifts, categorizing the barriers' impacts as either general to a screening shift or related to screening an individual youth/caregiver dyad. Using thematic content analysis, investigators further categorized barriers based on type (eg, workflow, language/comprehension, clinician attitudes/behaviors) and relationship to the limited integration of this initiative into clinical protocols. Reasons for refusal and descriptive data on barriers are also reported. RESULTS:Individual screen barriers were most often related to workflow (22.9%) and youth/caregiver language/comprehension challenges (28%). Similarly, workflow issues accounted for 48.2% of all general shift barriers. However, many of these barriers were related to the limited integration of the initiative, as RAs rather than clinical staff conducted the screening. CONCLUSIONS:Although this study was limited by a lack of complete integration into clinical protocols and was complicated by the COVID-19 pandemic impacts on PEDs, the findings suggest that considerable attention needs to be directed both to physician education and to workflow issues that could impede universal screening efforts.