Faculty Bibliography

Parental support and acceptance are strong protective factors for better mental health outcomes among transgender and gender diverse youth. Psychological inflexibility, specifically in the role of parenting, or “parenting inflexibility”, refers to an over-reliance on avoidance strategies at the expense of parenting values. Parenting inflexibility may be related to parental support, making it a useful target of intervention for parents of transgender youth. The aim of the present study was to develop a brief clinically useful measure of parenting inflexibility based on a synthesis of existing measures and to evaluate the psychometric properties across two study populations. Study 1 used exploratory factor analysis to examine this measure among parents in the general population recruited using MTurk. Study 2 used confirmatory factor analysis to examine the measure among parents of transgender youth recruited from a clinic. The final measure, the Impact of Parenting Avoidance (IPA) scale, is a one-factor 7-item measure of parenting inflexibility that is easy to administer and interpret in a pediatric health setting. The resulting measure demonstrated acceptable reliability, and it was significantly correlated with important outcome variables, such as negative parenting practices and lower perceived parental support among transgender and gender diverse youth.

INTRODUCTION/BACKGROUND:Maternal undernutrition and inflammation in utero may significantly impact the neurodevelopmental potential of offspring. However, few studies have investigated the effects of pregnancy interventions on long-term child growth and development. This study will examine the effects of prenatal nutrition and infection management interventions on long-term growth and neurodevelopmental outcomes of offspring. METHODS:The Enhancing Nutrition and Antenatal Infection Treatment ('ENAT') study (ISRCTN15116516) was a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. The study enrolled 2399 pregnant women who were randomised to receive routine care, an enhanced nutrition package (iron and folic acid, monthly household supply of iodised salt, and micronutrient-fortified balanced energy protein supplement for undernourished women), an enhanced infection management package (genitourinary tract infection screening and treatment, and enhanced deworming), or both packages. In the present Longitudinal Infant Development and Growth study, a subset of 480 children of mothers from ENAT will be recruited equally from each of the four study arms and visited at 12, 18, and 24 months of postnatal age. We will evaluate a range of domains and deploy multiple measures to assess child neurodevelopment, including resting electroencephalography and visual evoked potentials, Hammersmith Infant Neurological Examination, eye-tracking, Bayley Scales of Infant and Toddler Development (Bayley-III), and Magnetic Resonance Imaging (MRI). DISCUSSION/CONCLUSIONS:This study will advance understanding of the impact of nutrition and inflammation in pregnancy on long-term offspring neurodevelopment. This study aims to fill a critical knowledge gap on the benefits of prenatal interventions to promote the health of mothers and their offspring. ETHICS AND DISSEMINATION/BACKGROUND:This study was approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/IRB/002/2022) and Mass General Brigham (2023P000461). Results will be disseminated to local and international stakeholders. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT06296238.

PURPOSE/OBJECTIVE:Children and adolescents are experiencing a mental health crisis. Neurodiverse patients have high rates of mental health conditions and worse outcomes. To address this disparity, the Autism Spectrum Disorder Care Pathway was applied to a pediatric emergency department (PED) and Observation Unit (OU) in order to decrease agitation experienced by these patients. METHODS:This prospective cohort study was in a community-based PED and OU from June 2023 to February 2024. A medical education curriculum consisting of a multidisciplinary champion training and toolkit rollout was completed. Agitation was measured by the Behavioral Activity Rating Scale. The primary aim was to decrease frequency of agitation experienced by neurodiverse patients at any point in the PED/OU. The secondary outcome was to decrease pharmacologic intervention and physical restraint use. RESULTS:We captured data from a total of 45 patients, with 19 baseline patients and 26 patients in the intervention group. At baseline, 9 out of 19 (47%) patients experienced agitation at some point in their PED/OU stay. After implementation of the curriculum, agitation levels decreased to 6 out of 26 (23%) patients (p = 0.04). Inter-rater reliability was 0.95. There were 3 incidences of pharmacologic intervention and no physical restraint use. CONCLUSIONS:This pilot medical education curriculum for PED and OU staff members decreased agitation in neurodiverse patients who presented for mental health complaints. This study is the foundation for expansion of the curriculum for use in general emergency departments.

Systematic reviews and meta-analyses have become crucial for evidence-based decision-making in recent decades. However, it is common for the results of multiple reviews on the same topic to be inconsistent, and it is widely recognised that the results of the reviews are not always effectively communicated to healthcare professionals and the lay public. This manuscript proposes a strategy to summarise and communicate the findings of previous systematic reviews and meta-analyses to wider audiences. The proposed approach couples the findings of umbrella reviews with the creation of open-access online platforms that present the results of these umbrella reviews in an accessible way to various stakeholders. The key potential methodological avenues of this approach are presented, and specific examples from the author's own works and those from other teams are provided. An accompanying website (https://u-reach.org/) has been designed to present this Umbrella-Review, Evaluation, Analysis, and Communication Hub (U-REACH) approach and to overcome the technical challenges associated with this type of project (by sharing the code used to build existing U-REACH projects). The present document is intended to serve as a methodological and technical guide for the creation of large-scale projects designed to synthesise and disseminate scientific information to a broad audience.

Numerous recommendations have been made to address the high rates of mental health disorders among justice-involved youth. Few data are available on the use, quality, appropriateness, or availability of services to address these needs. This study examined the relationship between trauma-informed mental health screening, other referral pathways for diagnostic evaluation, subsequent DSM-5 diagnoses, and treatments for evaluated youth. Eligible participants were all youth admitted to New York City secure juvenile detention facilities from September 17, 2015 to October 30, 2016 who remained in the facility for at least five days (N = 786). Of those, 581 (73.9%) were voluntarily screened and 309 (53.2%) later received a diagnostic evaluation. Youth who screened positive for depression, posttraumatic stress disorder, and problematic substance use were more likely to be evaluated. Treatment received was related to diagnosis rather than reason for referral. For youth who were referred for behavioral or emotional concerns, 99.1 percent (114 of 115) of those diagnosed with a neurodevelopmental disorder had attention-deficit/hyperactivity disorder (ADHD). These data are among the first to describe DSM-5 diagnoses and treatment among youth detainees. They highlight the prevalence of ADHD in detained youth and argue for the coordination of universal trauma-informed mental health screening and a structured referral system for this population.

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC). Additionally, we explored their linked gene expression patterns in silico. Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes: the middle frontal gyrus of the frontoparietal network and posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD symptoms. Results from segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC interactions for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to: (i) have greater rate of variance in autism and ADHD, and (ii) be involved in neuron projection, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. Overall, these findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined phenomena to shared presentations at the macroscale circuit- and genomic-levels among children with diagnoses of autism and ADHD.

BACKGROUND:Clinical guidelines remain unclear on which medications for gambling disorder are to be preferred in terms of efficacy and tolerability. We aimed to compare pharmacological treatments for gambling disorder in terms of efficacy and tolerability, using network meta-analysis (NMA). METHODS:Based on our pre-registered protocol [CRD42022329520], a structured search was conducted across broad range of databases, for double-blind randomized controlled trials (RCTs) of medications for gambling disorder. Data were independently extracted by two researchers. We used standardized mean differences (SMD) using Hedges' g to measure the efficacy outcomes, and for the effect for tolerability we used dropout rate due to medication side effects, expressed as odds ratio (OR). Confidence in the network estimates was assessed using the CINeMA framework. We followed the PRISMA-NMA guidelines for this work. Outcomes were gambling symptom severity and quality of life (for efficacy), and tolerability. FINDINGS/RESULTS:We included 22 RCTs in the systematic review and 16 RCTs (n = 977 participants) in the NMA. Compared with placebo, moderate confidence evidence indicated that nalmefene [Standardized Mean Difference (SMD): -0.86; 95 % confidence interval (CI: -1.32,-0.41)] reduced gambling severity, followed by naltrexone (SMD: -0.42; 95 %CI: (-0.85,0.01)). Naltrexone (SMD: -0.50; 95 %CI: (-0.85,-0.14)) and nalmefene (SMD: -0.36; 95 %CI: (-0.72,-0.01) were also more beneficial than placebo in terms of quality of life. Olanzapine and topiramate were not more efficacious than placebo. Nalmefene [Odds Ratio (OR): 7.55; 95 %CI: (2.24-25.41)] and naltrexone (OR: 7.82; 95 %CI: (1.26-48.70)) had significantly higher dropout due to side effects (lower tolerability) compared with placebo. INTERPRETATION/CONCLUSIONS:Based on NMA, nalmefene and naltrexone currently have the most supportive evidence for the pharmacological treatment of gambling disorder. Further clinical trials of novel compounds, and analysis of individual participant data are needed, to strengthen the evidence base, and help tailor treatments at the individual patient level.

OBJECTIVE:Sleep problems are highly prevalent and impairing in adolescents with ADHD. However, their relation with co-occurring mental health problems is still unclear. This study assessed whether adolescents with ADHD, with and without self-reported sleep problems, differ from each other in co-occurring mental health problems, and whether they differ from adolescents without ADHD. Furthermore, we examined whether the adolescents with ADHD and self-reported sleep problems do indeed have more disturbed sleep than the other two groups and lastly, whether these sleep differences are moderated by co-occurring mental health problems. METHOD/METHODS:Three groups of adolescents (13-17 years): 1) with ADHD and comorbid self-reported sleep problems (N = 56), 2) with ADHD but without self-reported sleep problems (N = 25), and 3) without ADHD (N = 56) were assessed. Group comparisons were done for symptoms of co-occurring mental health problems, self- and parent-reported sleep problems, and objective and subjective sleep parameters. Exploratively, moderating effects of co-occurring mental health problems on sleep differences between groups are examined. RESULTS:Compared to those without self-reported sleep problems, adolescents with ADHD and comorbid self-reported sleep problems experienced significantly more co-occurring symptoms of mental health problems, especially depression. They also scored higher on all sleep problems, and had a longer sleep onset latency and lower sleep efficiency based on subjective and objective sleep measures. Depression and anxiety moderated objectively measured sleep differences. CONCLUSION/CONCLUSIONS:Co-occurring mental health problems, especially depressive symptoms, are more prevalent in adolescents with ADHD and sleep problems and partially moderate the relation with sleep. This indicates that when adolescents with ADHD present with sleep problems in clinical practice, it is essential to also assess symptoms and other mental health problems and vice-versa.

INTRODUCTION/BACKGROUND:ADHD has been linked to an increased risk of completed suicide. The aim of this study was to assess the relationship between ADHD medication use and completed suicide. METHODS:This nested case-control study included individuals aged 12-49 in Quebec, Canada, diagnosed with ADHD and/or dispensed ADHD medication. Suicide cases (n = 472) between 2000 and 2021 were matched with 5 controls each (n = 2360) on date of birth, sex, and continuous public drug insurance coverage for at least 365 days before suicide death (index date). Multivariable conditional logistic regression was used to estimate the association between ADHD medication use and completed suicide. The association between specific ADHD medication types and completed suicide was also assessed. RESULTS:After controlling for potential confounders, no significant association was found between ADHD medication use and completed suicide in the overall sample, in individuals aged 12-24 and 25 to 49 years, and those with a prior ADHD physician diagnosis. No significant differences were found when comparing the use of non-stimulants only (aOR 1.27; 95 % CI: 0.62, 2.63), stimulants and non-stimulants (aOR 1.01; 95 % CI: 0.33, 3.08), and ADHD consultation without medication (aOR 0.94; 95 % CI: 0.69, 1.28) against stimulant-only use. CONCLUSION/CONCLUSIONS:Both stimulants and non-stimulants were not associated with the risk of completed suicide. These findings can inform clinical decision-making.

PURPOSE/OBJECTIVE:Substantial evidence suggests a downstream impact of maternal mental health on birth outcomes. The roles of comorbid maternal physical health and familial confounding underlying this association remain unclear. METHODS:This cohort study included a random sample of children born 1997-2008 within a health maintenance organization (HMO) in Israel, their parents, and siblings. Outcomes were ICD-9 diagnoses of neonatal adversities (birth complications and congenital anomalies) and exposures were maternal diagnoses of mental health disorders. Odds ratios (ORs) and their 95% confidence intervals for the associations between maternal mental health diagnoses and measures of neonatal adversity were calculated using logistic regression, adjusting for maternal age, child's year of birth, socioeconomic status, and maternal physical morbidity burden. We examined potential familial confounding using a negative control approach based on paternal exposure. RESULTS:=1.1 (1.0-1.2), p = 0.01). CONCLUSION/CONCLUSIONS:Physical health and familial factors play a role in the associations between maternal mental health and neonatal adversity.