Faculty Bibliography

BACKGROUND:Children's social-emotional development and mental well-being are critical to adult mental health. However, little is known about the mechanisms or factors that contribute to poor child mental health in low- and middle-income countries. Given the lack of child mental health research to guide interventions or social-emotional learning programs and policy planning, the present study aimed to address these knowledge gaps by examining the psychopathology mechanism involved in the development of childhood mental health problems. METHODS:This cross-sectional study recruited parents (N = 393) whose children attended preschool to primary classes in the Arghakhanchi district of Nepal. Data were gathered through parent interviews. Structural Equation Modeling was used to examine the pathways of the mediational mechanism that examined the influence of parental well-being on parenting and children's mental health outcomes. RESULTS:Approximately 22% of the parents were at risk for moderate to severe mental health problems (anxiety: 24%, depression:19%). Parental mental health problems were higher in families who reported food insecurity, among female parents, less educated parents, and those who perceived themselves on a lower social ladder. Parental mental health, social support, and perceived class were associated with parent-child conflict. Greater parent-child conflict was associated with decreased social competence and increased anger, anxiety, and depression in children. CONCLUSION/CONCLUSIONS:The results partially support the mediational model that Nepali parents' well-being (especially in mental health symptoms, social support, and perception of family's social class domains) is associated with less optimal parenting and, in turn, greater child mental health problems and lower social competence. This study provides new evidence of cross-cultural consistency in child psychopathology and guides the development of evidence-based programs to prevent and promote mental health among Nepali children and families.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting α helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and "specificity residues" impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins.

IMPORTANCE/UNASSIGNED:Delivery of mental health care through telehealth (telemental health care) increased after the onset of the COVID-19 pandemic. Little is known about the speed of adoption (diffusion) of telemental health in the care in the care of individuals with schizophrenia. OBJECTIVES/UNASSIGNED:To characterize telemental health care diffusion in mental health agencies serving Medicaid beneficiaries with schizophrenia and the beneficiary-level association of telemental health care use with race and ethnicity. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used New York State Medicaid data from March 1, 2019, to February 29, 2020 (prepandemic period), and from March 11, 2020, to March 31, 2021 (pandemic period), from 261 agencies serving 30 990 beneficiaries with schizophrenia with 1 or more mental health visits during the pandemic period. Statistical analysis was performed from November 2021 through September 2024. EXPOSURE/UNASSIGNED:Agency percentage of patients belonging to racial and ethnic minority groups among all Medicaid-covered patients between March 2019 and February 2020; agency type, categorized as freestanding, hospital affiliated, or state operated; beneficiary-level race and ethnicity, categorized as Asian or other (American Indian or Alaska Native; Native Hawaiian or Other Pacific Islander), Black, Latinx, White, and unknown; and pandemic severity, operationalized as COVID-19 hospitalization rates per 10 000 population in administratively defined catchment areas. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Days to 10% cumulative telemental health care use within agencies, as well as beneficiary-level time to first telemental health care visit and any telemental health care visit in catchment areas in times of varying pandemic severity. RESULTS/UNASSIGNED:In this cohort study of 261 agencies (18 [7%] state operated, 79 [30%] hospital affiliated, and 164 [63%] free standing) and 30 990 beneficiaries with schizophrenia (mean [SD] age, 43 [13] years; 59% male; 7% Asian or other, 38% Black, 20% Latinx, and 25% White), 6 agencies (2%) never adopted telemental health care, and 248 (95%) reached 10% cumulative telemental health care visits in a mean of 18 days. Mean (SD) agency prepandemic shares of beneficiaries belonging to racial or ethnic minority groups (56% [23%]) were not associated with telemental health care diffusion. Diffusion was faster in state-operated vs free-standing agencies (hazard ratio [HR], 2.44 [95% CI, 1.21-4.95]). Relative to White beneficiaries, time to first telemental health care visit was slower in every racial and ethnic minority group (Asian or other: HR, 0.93 [95% CI, 0.88-0.98]; Black: HR, 0.90 [95% CI, 0.87-0.93]; Latinx: HR, 0.95 [95% CI, 0.91-0.99]). Beneficiaries from at least 1 racial or ethnic minority group were less likely than White beneficiaries to have a telemental health care visit regardless of pandemic severity and area; differences narrowed when pandemic severity was higher (eg, in New York City, the odds ratio of Black beneficiaries having a telemental health care visit relative to White beneficiaries when the pandemic severity was high was 0.70 [95% CI, 0.63-0.79] but decreased to 0.59 [95% CI, 0.53-0.67] when the pandemic severity was low). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of Medicaid beneficiaries with schizophrenia, telemental health care diffused rapidly after the onset of the COVID-19 pandemic, particularly in state-operated agencies. Together, agency-level and beneficiary-level race and ethnicity findings suggest within-agency racial and ethnic differences in diffusion of telemental health care. States should monitor the diffusion of innovations across vulnerable populations.

IMPORTANCE/UNASSIGNED:Amid escalating mental health challenges among young individuals, intensified by the COVID-19 pandemic, analyzing postpandemic trends is critical. OBJECTIVE/UNASSIGNED:To examine mental health care utilization and prescription rates for children, adolescents, and young adults before and after the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This population-based time trend study used an interrupted time series analysis to examine mental health care and prescription patterns among the French population 25 years and younger. Aggregated data from the French national health insurance database from January 2016 to June 2023. Data were analyzed from September 2023 to February 2024. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The number of individuals with at least 1 outpatient psychiatric consultation, those admitted for full-time psychiatric hospitalization, those with a suicide attempt, and those receiving psychotropic medication was computed. Data were stratified by age groups and sex. Quasi-Poisson regression modeled deseasonalized data, estimating the relative risk (RR) and 95% CI for differences in slopes before and after the pandemic. RESULTS/UNASSIGNED:This study included approximately 20 million individuals 25 years and younger (20 829 566 individuals in 2016 and 20 697 169 individuals in 2022). In 2016, the population consisted of 10 208 277 of 20 829 566 female participants (49.0%) and 6 091 959 (29.2%) aged 18 to 25 years. Proportions were similar in 2022. Significant increases in mental health care utilization were observed postpandemic compared with the prepandemic period, especially among females and young people aged 13 years and older. Outpatient psychiatric consultations increased among women (RR, 1.13; 95% CI, 1.07-1.20), individuals aged 13 to 17 years (RR, 1.15; 95% CI, 1.06-1.23), and individuals aged 18 to 25 years (RR, 1.08; 95% CI, 1.03-1.14). Hospitalizations for suicide attempt increased among women (RR, 1.14; 95% CI, 1.02-1.27) and individuals aged 18 to 25 years (RR, 1.07; 95% CI, 1.03-1.12). Regarding psychotropic medications, almost all classes, except hypnotics, increased in prescriptions between 2016 and 2022 for females, with a particularly marked rise in the postpandemic period. For men, only increases in the prescriptions of antidepressants (RR, 1.03; 95% CI, 1.01-1.06), methylphenidate (RR, 1.09; 95% CI, 1.06-1.12), and medications prescribed for alcohol use disorders (RR, 1.08; 95% CI, 1.04-1.13) were observed, and these increases were less pronounced than for women (antidepressant: RR, 1.13, 95% CI, 1.09-1.16; methylphenidate: RR, 1.15; 95% CI, 1.13-1.18; alcohol use dependence: RR, 1.12; 95% CI, 1.08-1.16). Medications reserved for severe mental health situations, such as lithium or clozapine, were prescribed more frequently starting at the age of 6 years. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, an interrupted time-series analysis found a marked deterioration in the mental health of young women in France in the after the COVID-19 pandemic, accentuating a trend of deterioration that was already observed in the prepandemic period.

OBJECTIVE/UNASSIGNED:Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS/UNASSIGNED:Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. RESULTS/UNASSIGNED:Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. CONCLUSIONS/UNASSIGNED:PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.

Palliative care improves the quality of life for seriously ill patients, but misconceptions and knowledge gaps hinder its implementation in home healthcare (HHC). This study developed and pilot-tested HHC-specific questionnaires to measure palliative care knowledge, attitudes, and confidence (PC-KAC) among clinicians, patients, and caregivers. Using literature reviews, expert input, and cognitive interviews, the questionnaires were refined to ensure clarity, practical relevance, and content validity. Pilot testing revealed widespread confusion about palliative care, with patients and caregivers often conflating it with hospice care and holding misconceptions about opioid use for pain and symptom management. While clinicians demonstrated adequate knowledge, gaps in pain management and confidence in handling emergencies were evident. These findings highlight the need for targeted education and training to integrate palliative care effectively into HHC, improving patient outcomes and supporting interdisciplinary collaboration.

BACKGROUND:COVID infection has been associated with long term sequalae (Long COVID) which include neurological and behavioral effects in thousands of patients, but the etiology and scope of symptoms is not well understood. This paper reviews long term sequelae of COVID on brain and mental health in patients with the Long COVID syndrome. METHODS:This was a literature review which queried databases for Pubmed, Psychinfo, and Medline for the following topics for January 1, 2020-July 15, 2023: Long COVID, PASC, brain, brain imaging, neurological, neurobiology, mental health, anxiety, depression. RESULTS:Tens of thousands of patients have developed Long COVID, with the most common neurobehavioral symptoms anosmia (loss of smell) and fatigue. Anxiety and mood disorders are elevated and seen in about 25% of Long COVID patients. Neuropsychological testing studies show a correlation between symptom severity and cognitive dysfunction, while brain imaging studies show global decreases in gray matter and alterations in olfactory and other brain areas. CONCLUSIONS:Studies to date show an increase in neurobehavioral disturbances in patients with Long COVID. Future research is needed to determine mechanisms.

Glutamatergic dentate gyrus (DG) mossy cells (MCs) innervate the primary DG cell type, granule cells (GCs). Numerous MC synapses are on GC proximal dendrites in the inner molecular layer (IML). However, field recordings of the GC excitatory postsynaptic potential (fEPSPs) have not been used to study this pathway selectively. Here we describe methods to selectively activate MC axons in the IML using mice with Cre recombinase expressed in MCs. Slices were made after injecting adeno-associated virus (AAV) encoding channelrhodopsin (ChR2) in the DG. In these slices, we show that fEPSPs could be recorded reliably in the IML in response to optogenetic stimulation of MC axons. Furthermore, fEPSPs were widespread across the septotemporal axis. However, fEPSPs were relatively weak because they were small in amplitude and did not elicit a significant population spike in GCs. They also showed little paired pulse facilitation. We confirmed the extracellular findings with patch clamp recordings of GCs despite different recording chambers and other differences in methods. Together the results provide a simple method for studying MC activation of GCs and add to the evidence that this input is normally weak but widespread across the GC population.

BACKGROUND:The comparative benefits and harms of available interventions for ADHD in adults remain unclear. We aimed to address these important knowledge gaps. METHODS:In this systematic review and component network meta-analysis (NMA), we searched multiple databases for published and unpublished randomised controlled trials (RCTs) investigating pharmacological and non-pharmacological interventions for ADHD in adults from database inception to Sept 6, 2023. We included aggregate data from RCTs comparing interventions against controls or any other eligible active intervention for the treatment of symptoms in adults (ages ≥18 years) with a formal diagnosis of ADHD. Pharmacological therapies were included only if their maximum planned doses were considered eligible according to international guidelines. We included RCTs of at least 1-week duration for medications, of at least four sessions for psychological therapies, and of any length deemed appropriate for neurostimulation. For RCTs of medications, cognitive training, or neurostimulation alone, we included only double-blind RCTs. At least two authors independently screened the identified records and extracted data from eligible RCTs. Our primary outcomes were efficacy (change in ADHD core symptom severity on self-rated and clinician-rated scales at timepoints closest to 12 weeks) and acceptability (all-cause discontinuation). We estimated standardised mean differences (SMDs) and odds ratios (ORs) using random effects pairwise and component NMA, dismantling interventions into specific therapeutic components. This study was registered with PROSPERO (CRD42021265576). People with relevant lived experience were involved in the conduct of the research and writing process. FINDINGS/RESULTS:Of 32 416 records, 113 unique RCTs encompassing 14 887 participants were eligible for analysis (6787 [45·6%] females, 7638 [51·3%] males, 462 [3·1%] sex not reported). The RCTs encompassed pharmacological therapies (63 [55·8%] of 113 RCTs; 6875 participants), psychological therapies (28 [24·8%] of 113 RCTs; 1116 participants), neurostimulatory therapy and neurofeedback (ten [8·8%] of 113 RCTs; 194 participants), and control conditions (97 [85·8%] of 113 RCTs; 5770 participants). For reduction of ADHD core symptoms at 12 weeks on both self-reported and clinician-reported rating scales, atomoxetine (self-reported scale SMD -0·38, 95% CI -0·56 to -0·21; clinician-reported scale -0·51, -0·64 to -0·37) and stimulants (0·39, -0·52 to -0·26; -0·61, -0·71 to -0·51) had higher efficacy than placebo (Confidence in Network Meta-Analysis [CINeMA] ranging between very low and moderate). Cognitive behavioural therapy (-0·76, -1·26 to -0·26), cognitive remediation (-1·35, -2·42 to -0·27), mindfulness (-0·79, -1·29 to -0·29), psychoeducation (-0·77, -1·35 to -0·18), and transcranial direct current stimulation (-0·78; -1·13 to -0·43) were better than placebo only on clinician-reported measures. Regarding acceptability, all therapeutic components were similar to placebo other than atomoxetine (OR 1·43, 95% CI 1·14 to 1·80; CINeMA moderate) and guanfacine (3·70, 1·22 to 11·19; high), which had lower acceptability compared with placebo. Baseline severity of self-reported ADHD core symptoms, year of publication, percentage of male individuals, and percentage of individuals with ADHD and another mental health condition did not explain the heterogeneity observed in unadjusted non-component models of self-reported ADHD core symptoms. Treatment length had little effect on heterogeneity. INTERPRETATION/CONCLUSIONS:Stimulants and atomoxetine were the only interventions with evidence of beneficial effects in terms of reducing ADHD core symptoms in the short term, supported by both self-reported and clinician-reported ratings. However, atomoxetine was less acceptable than placebo. Medications for ADHD were not efficacious on additional relevant outcomes, such as quality of life, and evidence in the longer term is underinvestigated. The effects of non-pharmacological strategies were inconsistent across different raters. Our network meta-analysis represents the most comprehensive synthesis of available evidence to inform future guidelines in the field. FUNDING/BACKGROUND:UK National Institute for Health and Care Research.

Gestational diabetes mellitus (GDM) affects around 10% of pregnancies in the United States and has been linked to neurodevelopmental sequelae in children. However, there is a paucity of studies investigating early-life neural markers in GDM-exposed infants. This study examined the association of GDM with relative EEG power among healthy term-age neonates collected during natural sleep. Participants included a diverse cohort of 101 mothers (45% multiracial, 25% Black, and 69% Hispanic or Latina) and their infants (gestational age at birth M_age = 39.0 ± 0.95; 46.5% female). We did not observe the main effect of GDM on infant relative EEG power. Our post hoc analyses revealed a significant interaction effect between GDM and infant birth weight on relative EEG power in active sleep. Among GDM-exposed neonates, increased birth weight was associated with increased relative theta EEG power and decreased relative beta and gamma EEG power across multiple electrode regions. Among non-GDM-exposed infants, increased birth weight was associated with decreased relative theta EEG power and increased relative beta and gamma EEG power across multiple electrode regions. Our findings suggest that alterations in fetal growth may serve as either an indirect marker or pathway through which GDM influences the developing fetal brain.