Faculty Bibliography

Individuals with DS develop Alzheimer's disease (AD) neuropathology, including endosomal-lysosomal system abnormalities and degeneration of basal forebrain cholinergic neurons (BFCNs). We investigated whether maternal choline supplementation (MCS) affects early endosome pathology within BFCNs using the Ts65Dn mouse model of DS/AD. Ts65Dn and disomic (2N) offspring from dams administered MCS were analyzed for endosomal pathology at 3-4 months or 10-12 months. Morphometric analysis of early endosome phenotype was performed on individual BFCNs using Imaris. The effects of MCS on the endosomal interactome were interrogated by relative co-expression (RCE) analysis. MCS effectively reduced age- and genotype-associated increases in early endosome number in Ts65Dn and 2N offspring, and prevented increases in early endosome size in Ts65Dn offspring. RCE revealed a loss of interactome cooperativity among endosome genes in Ts65Dn offspring that was restored by MCS. These findings demonstrate MCS rescues early endosome pathology, a driver of septohippocampal circuit dysfunction. The genotype-independent benefits of MCS on endosomal phenotype indicate translational applicability as an early-life therapy for DS as well as other neurodevelopmental/neurodegenerative disorders involving endosomal pathology.

BACKGROUND:While it is recognized that social support can alleviate mental health symptoms, this relationship is not well-understood among Chinese pregnant and parenting immigrants in the United States. This study aims to bridge this gap by exploring the relationships between different types of social support and women's anxiety and depression, and examining how these associations vary with pregnancy status. METHODS:Data were obtained from a cross-sectional survey conducted in Simplified Chinese or Mandarin between March-June 2021 among 526 women who were pregnant and/or parenting a child under five years. The Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Depression, and Social Support scales were used to measure anxiety, depression, and social support levels. Descriptive statistics, t-tests, chi-square tests, and Pearson's correlations were employed for analysis. Hierarchical regression was conducted to investigate the main and interaction effects of social support types and pregnancy status on mental health outcomes. RESULTS:Compared to non-pregnant women, pregnant women reported higher mean scores for anxiety (non-pregnant: 55, pregnant: 59, p < 0.01) and depression (non-pregnant: 54, pregnant: 56, p = 0.02). Instrumental support displayed a significant main effect in relation to anxiety (β=-0.13, p = 0.01) and depression (β=-0.16, p < 0.01); emotional support exhibited a significant main effect solely on depression (β=-0.13, p = 0.01). Notably, the interaction effects between pregnancy status and both instrumental (β=-0.28, p = 0.01) and emotional support (β=-0.42, p < 0.01) were significant for anxiety. In contrast, informational support did not exhibit a significant impact on either anxiety or depression. CONCLUSIONS:The findings indicate that tailoring support to the cultural context is crucial, especially for pregnant women in this Chinese immigrant community, with instrumental and emotional support being particularly beneficial in mitigating maternal anxiety.

Autistic youth are more likely to experience maltreatment, victimization, and other traumatic events. However, it can be difficult to identify trauma-related symptoms in autistic youth, especially in those with limited verbal communication. In this study, we compared the prevalence of trauma-related diagnoses given to youth with autism spectrum disorder (ASD) to those given to youth without ASD who presented to a specialized pediatric psychiatric emergency department. We found that youth with ASD were 42% less likely to receive trauma-related diagnoses than youth without ASD. As there is evidence that youth with ASD are no less likely to experience traumatic events compared with youth without ASD, one possible explanation for this result is that trauma-related symptoms are missed during emergency psychiatric evaluations. Developing trauma screening instruments specifically designed for the needs of youth with ASD is an outstanding need.

We carried out the first systematic review to gauge if assessment of blinding was conducted in RCTs investigating medications for ADHD. Put of 161 RCTs form the dataset MED-ADHD (https://med-adhd.org/), we found only one RCT that reported blinding integrity, indicating that assessments of blinding integrity are very rarely conducted in the field. While our findings are not meant to invalidate the evidence on the benefits of ADHD medications, they suggest an opportunity to improve reporting of clinical trials in ADHD.

IMPORTANCE/UNASSIGNED:Increasing numbers of unaffected individuals could benefit from genetic evaluation for inherited cancer susceptibility. Automated conversational agents (ie, chatbots) are being developed for cancer genetics contexts; however, randomized comparisons with standard of care (SOC) are needed. OBJECTIVE/UNASSIGNED:To examine whether chatbot and SOC approaches are equivalent in completion of pretest cancer genetic services and genetic testing. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This equivalence trial (Broadening the Reach, Impact, and Delivery of Genetic Services [BRIDGE] randomized clinical trial) was conducted between August 15, 2020, and August 31, 2023, at 2 US health care systems (University of Utah Health and NYU Langone Health). Participants were aged 25 to 60 years, had had a primary care visit in the previous 3 years, were eligible for cancer genetic evaluation, were English or Spanish speaking, had no prior cancer diagnosis other than nonmelanoma skin cancer, had no prior cancer genetic counseling or testing, and had an electronic patient portal account. INTERVENTION/UNASSIGNED:Participants were randomized 1:1 at the patient level to the study groups at each site. In the chatbot intervention group, patients were invited in a patient portal outreach message to complete a pretest genetics education chat. In the enhanced SOC control group, patients were invited to complete an SOC pretest appointment with a certified genetic counselor. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were completion of pretest cancer genetic services (ie, pretest genetics education chat or pretest genetic counseling appointment) and completion of genetic testing. Equivalence hypothesis testing was used to compare the study groups. RESULTS/UNASSIGNED:This study included 3073 patients (1554 in the chatbot group and 1519 in the enhanced SOC control group). Their mean (SD) age at outreach was 43.8 (9.9) years, and most (2233 of 3063 [72.9%]) were women. A total of 204 patients (7.3%) were Black, 317 (11.4%) were Latinx, and 2094 (75.0%) were White. The estimated percentage point difference for completion of pretest cancer genetic services between groups was 2.0 (95% CI, -1.1 to 5.0). The estimated percentage point difference for completion of genetic testing was -1.3 (95% CI, -3.7 to 1.1). Analyses suggested equivalence in the primary outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of the BRIDGE equivalence trial support the use of chatbot approaches to offer cancer genetic services. Chatbot tools can be a key component of sustainable and scalable population health management strategies to enhance access to cancer genetic services. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03985852.

The goal of our study was to describe the availability of community child and adolescent mental health services, trauma-informed care, and the geographic accessibility of these services for juvenile justice-involved (JJ) youth who received mental health services while in secure detention. Data collection occurred through direct contact with the child and adolescent outpatient clinics listed on the New York State Office of Mental Health website. Zip codes were collected from the juvenile secure detention census. Of the clinics contacted, 88.5 percent accepted JJ youth; however, 43.5 percent accepted them on a conditional basis. Only 62.1 percent offered trauma-informed care, including evidence-based interventions and unspecified care. Although 84.5 percent of the clinics that would accept this population reported currently accepting new patients, reported wait times were as high as six or more months. When JJ residents' home zip codes and those of the clinics were geographically mapped, there were few clinics in the zip codes where most residents lived. The clinics that accepted youth on a conditional basis often refused high-risk patients, essentially ruling out a large majority of this population. The geographical inaccessibility of these clinics limits their ability to provide care for this vulnerable population.

IMPORTANCE/UNASSIGNED:Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly common. Individuals with NDDs have heightened obesity risks, but long-term data on body mass index (BMI) trends over time in this population are lacking. OBJECTIVE/UNASSIGNED:To assess secular BMI changes from 2004 to 2020 among children with NDDs compared with those without NDDs. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This repeated cross-sectional study used data from the Child and Adolescent Twin Study in Sweden. Children born between January 1, 1992, and December 31, 2010, were screened for neurodevelopmental symptoms using the Autism-Tics, ADHD, and Other Comorbidities inventory between July 2004 and April 2020 when they were 9 or 12 years of age. Data analysis was conducted between September 27, 2023, and January 30, 2024. MAIN OUTCOMES AND MEASURES/UNASSIGNED:BMI percentiles (15th, 50th, and 85th) were modeled using quantile regression and compared between youths with and without NDDs. Secular changes in BMI percentiles over time spanning 2004 to 2020 were evaluated and stratified by NDD subtype. RESULTS/UNASSIGNED:The cohort included 24 969 Swedish twins (12 681 [51%] boys) born between 1992 and 2010, with mean (SD) age of 9 (0.6) years. Of these, 1103 (4%) screened positive for 1 or more NDDs, including ADHD, ASD, and/or learning disability. Results indicated that at the 85th BMI percentile, there was a greater increase in BMI from 2004 to 2020 among youths with NDDs compared with those without NDDs (β for interaction [βint] between NDD status and time, 1.67; 95% CI, 0.39-2.90). The greatest divergence was seen for ASD (βint, 2.12; 95% CI, 1.26-3.70) and learning disability (βint, 1.92; 95% CI, 0.65-3.82). Within the latest cohort (2016-2020), the 85th BMI percentile was 1.99 (95% CI, 1.08-2.89) points higher among children with NDDs compared with those without NDDs. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this repeated cross-sectional study, at the higher end of the BMI distribution, children with NDDs had significantly greater increases in BMI compared with peers without NDDs over a 16-year period, highlighting an increasing risk of overweight over time in youths with NDDs compared with those without NDDs. Targeted obesity prevention efforts for this high-risk population are needed.

IMPORTANCE/UNASSIGNED:Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. OBJECTIVE/UNASSIGNED:To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. EXPOSURES/UNASSIGNED:Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. RESULTS/UNASSIGNED:The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

Efforts to bolster the school readiness of Latinx children from low-income homes in the United States have focused on fostering parent engagement in children"™s education. Measurement of parent engagement in early childhood however, has been critiqued for having too narrow a focus on school-based involvement and missing other aspects of Latinx parent engagement. Using a recently developed culturally sensitive assessment of Latinx parent engagement, we test for associations between dimensions of Latinx parent engagement in learning and indicators of school readiness in a diverse sample of Latinx families (n = 114). We find significant associations between multiple dimensions of Latinx parent engagement and indicators of child school readiness. In addition to promoting parent-teacher connections, efforts to support Latinx school readiness equitably are encouraged to attend to various culturally relevant aspects of Latinx parent engagement in early childhood. In particular, investing in programing that supports parents"™ well-being and capacity for home-based engagement in learning may be a promising way to support the school readiness of Latinx children living in historically disinvested neighborhoods.

BACKGROUND/UNASSIGNED:Over the last decades, the prevalence of Attention-deficit/hyperactivity disorder (ADHD) has increased. However, the underlying explanation for this increase remains unclear. We aimed to assess whether there has been a secular change in how parents perceive the impairment conferred by ADHD symptomatology. METHODS/UNASSIGNED:Data for this study were obtained from the Child and Adolescent Twin Study in Sweden, involving 27,240 individuals whose parents answered a questionnaire when the children were 9 years old. We assessed the relationship between parentally perceived impairment caused by ADHD symptoms scores over time. The analysis was performed separately for five different birth cohorts, spanning three-year periods from 1995 to 2009 and for ADHD inattention and hyperactivity/impulsivity dimensions. RESULTS/UNASSIGNED:We found a consistent upward trend of parents reporting impairment in relation to ADHD symptomatology across birth cohorts. Over a 12-year period, comparing those born 2007-2009 (assessed 2016-2018) with those born 1995-1997 (assessed 2004-2006), impairment scores increased by 27% at clinically relevant levels of ADHD symptomatology. Notably, when specifically evaluating the hyperactivity/impulsivity dimension, the disparity was even more striking, with an increase of up to 77%. CONCLUSIONS/UNASSIGNED:This study revealed a significant secular change in parental perception of impairment attributed to ADHD symptomatology over recent decades, providing new insights into the increased prevalence of ADHD. It underscores the need to better understand the factors that have contributed to the increased perception of impairment related to ADHD symptoms.