Faculty Bibliography

Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.gov website all the 157 pharmacological and nutraceutical compounds which have been experimentally tested in children and adolescents with ASD using the randomized placebo-controlled trial (RCT) design. After excluding 24 drugs already presented in Part I, a systematic review spanning each of the remaining 133 compounds was registered on Prospero (ID: CRD42023476555), performed on PubMed (August 8, 2024), and completed with EBSCO, PsycINFO (psychology and psychiatry literature) and the Cochrane Database of Systematic reviews, yielding a total of 115 published RCTs, including 57 trials for 23 pharmacological compounds and 48 trials for 17 nutraceuticals/supplements. Melatonin and oxytocin were not included, because recent systematic reviews have been already published for both these compounds. RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation. For the vast majority of compounds, including cannabidiol, vasopressin, and probiotics, insufficient evidence of efficacy and safety is available. However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize "drug-based" information, which will be ultimately merged to provide clinicians with a "symptom-based" consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials.

Individual differences in how the brain responds to novelty are present from infancy. A common method of studying novelty processing is through event-related potentials (ERPs). While ERPs possess millisecond precision, spatial resolution remains poor, especially in infancy. This study aimed to balance spatial and temporal precision by combining ERP data with functional magnetic resonance imaging (fMRI) data. Twenty-nine infants (15 female) underwent resting-state fMRI (M

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.

PURPOSE/OBJECTIVE:Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems. METHODS: Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age. RESULTS: In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales. CONCLUSION/CONCLUSIONS: Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems.

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.

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.

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.

Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24-2.12) or depression (1.65 [1.34-2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19-1.90]); and (3) major congenital malformation (1.24 [1.09-1.40]) or cardiac malformations (1.28 [1.11-1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.

Generative artificial intelligence (genAI) has potential to improve healthcare by reducing clinician burden and expanding services, among other uses. There is a significant gap between the need for mental health care and available clinicians in the United States-this makes it an attractive target for improved efficiency through genAI. Among the most sensitive mental health topics is suicide, and demand for crisis intervention has grown in recent years. We aimed to evaluate the quality of genAI tool responses to suicide-related queries. We entered 10 suicide-related queries into five genAI tools-ChatGPT 3.5, GPT-4, a version of GPT-4 safe for protected health information, Gemini, and Bing Copilot. The response to each query was coded on seven metrics including presence of a suicide hotline number, content related to evidence-based suicide interventions, supportive content, harmful content. Pooling across tools, most of the responses (79%) were supportive. Only 24% of responses included a crisis hotline number and only 4% included content consistent with evidence-based suicide prevention interventions. Harmful content was rare (5%); all such instances were delivered by Bing Copilot. Our results suggest that genAI developers have taken a very conservative approach to suicide-related content and constrained their models' responses to suggest support-seeking, but little else. Finding balance between providing much needed evidence-based mental health information without introducing excessive risk is within the capabilities of genAI developers. At this nascent stage of integrating genAI tools into healthcare systems, ensuring mental health parity should be the goal of genAI developers and healthcare organizations.