Faculty Bibliography

OBJECTIVE:To advance understanding of early childhood bed-sharing and its clinical significance, we examined reactive bed-sharing rates, sociodemographic correlates, persistence, and concurrent and longitudinal associations with sleep disturbances and psychopathology. METHODS:Data from a representative cohort of 917 children (mean age 3.8 years) recruited from primary pediatric clinics in a Southeastern city for a preschool anxiety study were used. Sociodemographics and diagnostic classifications for sleep disturbances and psychopathology were obtained using the Preschool Age Psychiatric Assessment (PAPA), a structured diagnostic interview administered to caregivers. A subsample of 187 children was re-assessed approximately 24.7 months after the initial PAPA interview. RESULTS:Reactive bed-sharing was reported by 38.4% of parents, 22.9% nightly and 15.5% weekly, and declined with age. At follow-up, 48.9% of nightly bed-sharers and 88.7% of weekly bed-sharers were no longer bed-sharing. Sociodemographics associated with nightly bed-sharing were Black and (combined) American Indian, Alaska Native and Asian race and ethnicity, low income and parent education less than high school. Concurrently, bed-sharing nightly was associated with separation anxiety and sleep terrors; bed-sharing weekly was associated with sleep terrors and difficulty staying asleep. No longitudinal associations were found between reactive bed-sharing and sleep disturbances or psychopathology after controlling for sociodemographics, baseline status of the outcome and time between interviews. CONCLUSIONS:Reactive bed-sharing is relatively common among preschoolers, varies significantly by sociodemographic factors, declines during the preschool years and is more persistent among nightly than weekly bed-sharers. Reactive bed-sharing may be an indicator of sleep disturbances and/or anxiety but there is no evidence that bed-sharing is an antecedent or consequence of sleep disturbances or psychopathology.

INTRODUCTION/BACKGROUND:The report examined reciprocal within-person associations among maternal depressive symptoms and offspring depressive, anxiety and irritability symptoms from early childhood to adolescence using a random intercept cross-lagged panel model (RI-CLPM). METHOD/METHODS:Participants were 609 mother-child dyads participating in the Stony Brook Temperament Study. Child and maternal internalizing symptoms were assessed every 3 years from ages 3 to 15 using maternal report on the Child Behavior Checklist (CBCL) and Diagnostic Inventory for Depression, respectively. RESULTS:At the between-person level, maternal depressive symptoms, and child depressive, anxiety, and irritability symptoms were all positively associated with one another. At the within-person level, greater within-person child anxiety symptoms at age 3 predicted both greater child anxiety and depressive symptoms at age 15 via greater child anxiety from ages 6 to 12, and greater within-person child irritability at age 3 predicted greater maternal depressive symptoms at age 15 via greater child irritability from ages 6 to 12. CONCLUSIONS:Findings reveal novel within-person developmental pathways from early childhood internalizing problems to later internalizing problems in both the child and mother. Intervention and prevention efforts should thus focus on early identification and prevention of childhood internalizing symptoms to reduce negative effects on both child and parent symptoms.

IMPORTANCE/UNASSIGNED:The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS/UNASSIGNED:cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE/UNASSIGNED:RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALSGOV IDENTIFIER/UNASSIGNED:Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.

Tobacco smoking is highly prevalent among patients with serious mental illness (SMI), with known deleterious consequences. Smoking cessation is therefore a prioritary public health challenge in SMI. In recent years, several smoking cessation digital interventions have been developed for non-clinical populations. However, their impact in patients with SMI remains uncertain. We conducted a systematic review to describe and evaluate effectiveness, acceptability, adherence, usability and safety of digital interventions for smoking cessation in patients with SMI. PubMed/MEDLINE, EMBASE, CINAHL, Web of Science, PsychINFO and the Cochrane Tobacco Addiction Group Specialized Register were searched. Studies matching inclusion criteria were included and their information systematically extracted by independent investigators. Thirteen articles were included, which reported data on nine different digital interventions. Intervention theoretical approaches ranged from mobile contingency management to mindfulness. Outcome measures varied widely between studies. The highest abstinence rates were found for mSMART MIND (7-day point-prevalent abstinence: 16-40%). Let's Talk About Quitting Smoking reported greater acceptability ratings, although this was not evaluated with standardized measures. Regarding usability, Learn to Quit showed the highest System Usability Scale scores [mean (s.d.) 85.2 (15.5)]. Adverse events were rare and not systematically reported. Overall, the quality of the studies was fair to good. Digitally delivered health interventions for smoking cessation show promise for improving outcomes for patients with SMI, but lack of availability remains a concern. Larger trials with harmonized assessment measures are needed to generate more definitive evidence and specific recommendations.

Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n> 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n=550,748; no ADHD n=14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for AD, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.

IMPORTANCE:Gender-diverse youths have higher rates of mental health problems compared with the general population, as shown in both clinical and nonclinical populations. Brain correlates of gender diversity, however, have been reported only among youths with gender dysphoria or in transgender individuals. OBJECTIVE:To examine brain morphologic correlates of gender diversity among adolescents from a general pediatric population who were assigned male or female at birth, separately. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study was embedded in Generation R, a multiethnic population-based study conducted in Rotterdam, the Netherlands. Adolescents who were born between April 1, 2002, and January 31, 2006, and had information on self-reported or parent-reported gender diversity and structural neuroimaging at ages 13 to 15 years were included. Data analysis was performed from April 1 to July 31, 2022. EXPOSURES:Gender-diverse experiences among adolescents were measured with selected items from the Achenbach System of Empirically Based Assessment forms and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults, as reported by adolescents and/or their parents. MAIN OUTCOMES AND MEASURES:High-resolution structural neuroimaging data were collected using a 3-T magnetic resonance imaging scanner (at a single site). We used linear regression models to examine differences in global brain volumetric measures between adolescents who reported gender diversity and those who did not. RESULTS:This study included 2165 participants, with a mean (SD) age of 13.8 (0.6) years at scanning. A total of 1159 participants (53.5%) were assigned female at birth and 1006 (46.5%) were assigned male at birth. With regard to maternal country of origin, 1217 mothers (57.6%) were from the Netherlands and 896 (42.4%) were from outside the Netherlands. Adolescents who reported gender diversity did not differ in global brain volumetric measures from adolescents who did not report gender diversity. In whole-brain, vertexwise analyses among adolescents assigned male at birth, thicker cortices in the left inferior temporal gyrus were observed among youths who reported gender diversity compared with those who did not. No associations were observed between gender diversity and surface area in vertexwise analyses. CONCLUSIONS AND RELEVANCE:The findings of this cross-sectional study suggest that global brain volumetric measures did not differ between adolescents who reported gender diversity and those who did not. However, these findings further suggest that gender diversity in the general population correlates with specific brain morphologic features in the inferior temporal gyrus among youths who are assigned male at birth. Replication of these findings is necessary to elucidate the potential neurobiological basis of gender diversity in the general population. Future longitudinal studies should also investigate the directionality of these associations.

IMPORTANCE:Autism spectrum disorder (ASD) is associated with significant clinical, neuroanatomical, and genetic heterogeneity that limits precision diagnostics and treatment. OBJECTIVE:To assess distinct neuroanatomical dimensions of ASD using novel semisupervised machine learning methods and to test whether the dimensions can serve as endophenotypes also in non-ASD populations. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study used imaging data from the publicly available Autism Brain Imaging Data Exchange (ABIDE) repositories as the discovery cohort. The ABIDE sample included individuals diagnosed with ASD aged between 16 and 64 years and age- and sex-match typically developing individuals. Validation cohorts included individuals with schizophrenia from the Psychosis Heterogeneity Evaluated via Dimensional Neuroimaging (PHENOM) consortium and individuals from the UK Biobank to represent the general population. The multisite discovery cohort included 16 internationally distributed imaging sites. Analyses were performed between March 2021 and March 2022. MAIN OUTCOMES AND MEASURES:The trained semisupervised heterogeneity through discriminative analysis models were tested for reproducibility using extensive cross-validations. It was then applied to individuals from the PHENOM and the UK Biobank. It was hypothesized that neuroanatomical dimensions of ASD would display distinct clinical and genetic profiles and would be prominent also in non-ASD populations. RESULTS:Heterogeneity through discriminative analysis models trained on T1-weighted brain magnetic resonance images of 307 individuals with ASD (mean [SD] age, 25.4 [9.8] years; 273 [88.9%] male) and 362 typically developing control individuals (mean [SD] age, 25.8 [8.9] years; 309 [85.4%] male) revealed that a 3-dimensional scheme was optimal to capture the ASD neuroanatomy. The first dimension (A1: aginglike) was associated with smaller brain volume, lower cognitive function, and aging-related genetic variants (FOXO3; Z = 4.65; P = 1.62 × 10-6). The second dimension (A2: schizophrenialike) was characterized by enlarged subcortical volumes, antipsychotic medication use (Cohen d = 0.65; false discovery rate-adjusted P = .048), partially overlapping genetic, neuroanatomical characteristics to schizophrenia (n = 307), and significant genetic heritability estimates in the general population (n = 14 786; mean [SD] h2, 0.71 [0.04]; P < 1 × 10-4). The third dimension (A3: typical ASD) was distinguished by enlarged cortical volumes, high nonverbal cognitive performance, and biological pathways implicating brain development and abnormal apoptosis (mean [SD] β, 0.83 [0.02]; P = 4.22 × 10-6). CONCLUSIONS AND RELEVANCE:This cross-sectional study discovered 3-dimensional endophenotypic representation that may elucidate the heterogeneous neurobiological underpinnings of ASD to support precision diagnostics. The significant correspondence between A2 and schizophrenia indicates a possibility of identifying common biological mechanisms across the 2 mental health diagnoses.

We conducted an observational study of a collection of interactive processes known as "demand-withdraw" in relation to adolescent dating aggression. Couples (N = 209) aged 14-18 years participated in a challenging observational laboratory assessment to measure demands (i.e., pressures for a change), as well as demand → partner withdraw and demand → partner avoid sequences. Actor and partner effects were disentangled via dyadic data analyses. The results indicated a fairly consistent pattern in which demand → withdraw and demand → avoid sequences led by either partner were positively associated with both partners' physical and psychological aggression (measured via a dual informant questionnaire method). Further, higher quality demands (i.e., pressures for change that were specific and encouraged both members of the dyad to increase a given behavior) were inversely associated with aggression. Yet, all of the above associations were attenuated to the point of statistical nonsignificance after controlling for hostility. These results suggest two primary possibilities. The associations of demand → withdraw and demand → avoid sequences with dating aggression may be spurious, with the sequences merely markers for hostility, a known correlate of dating aggression. Alternatively, hostility may mediate the relations of demand → withdraw and demand → avoid sequences with dating aggression. Further research is required to test these competing explanations. Implications for preventive intervention are discussed.