Faculty Bibliography

Depression is a major contributor to the global burden of disease. There is limited understanding of how environmental exposures may contribute to depression etiology. We used Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine associations between low-level ambient air pollution exposure and depressed mood in a generally healthy population of over 10,000 24-32 year olds. Annual mean PM2.5 levels in the 2008-2009 study were close to the current U.S. standard. In fully adjusted quasi-binomial logistic regression models, there were no meaningful associations between IQR increases in air pollutant and change in depressed mood status regardless of specific pollutant or moving average lags. In interaction effects models, an IQR increase in lag day 0-30 PM2.5 resulted in 1.20 (95% CI, 1.02-1.41) times higher likelihood of having depressed mood, but only for persons with chronic lung disease (interaction P=0.04); the association was null for participants without chronic lung disease (OR 0.98, 95% CI, 0.91, 1.05). Our findings suggest that among persons with a lifetime history of chronic lung disease, greater exposure to even low-level PM2.5, PM10, and sulfate may be associated with modest increases in the likelihood of having depressed mood.

Given the chronic nature of schizophrenia, it is important to examine age-specific prevalence and incidence to understand the scope of the burden of schizophrenia across the lifespan. Estimates of lifetime prevalence of schizophrenia have varied widely and have often relied upon community-based data estimates from over two decades ago, while more recent studies have shown considerable promise by leveraging pooled datasets. However, the validity of measures of schizophrenia, particularly new onset schizophrenia, has not been well studied in these large health databases. The current study examines prevalence and validity of incidence measures of new diagnoses of schizophrenia in 2019 using two U.S. administrative health databases: MarketScan, a national database of individuals receiving employer-sponsored commercial insurance (N = 16,365,997), and NYS Medicaid, a large state public insurance program (N = 4,414,153). Our results indicate that the prevalence of schizophrenia is over 10-fold higher, and the incidence two-fold higher, in the NYS Medicaid population compared to the MarketScan database. In addition, prevalence increased over the lifespan in the Medicaid population, but decreased in the employment based MarketScan database beginning in early adulthood. Incident measures of new diagnoses of schizophrenia had excellent validity, with positive predictive values and specificity exceeding 95%, but required a longer lookback period for Medicaid compared to MarketScan. Further work is needed to leverage these findings to develop robust clinical outcome predictors for new onset of schizophrenia within large administrative health data systems.

IMPORTANCE/UNASSIGNED:Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment. OBJECTIVE/UNASSIGNED:To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history. EXPOSURE/UNASSIGNED:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:PASC and 89 prolonged symptoms across 9 symptom domains. RESULTS/UNASSIGNED:A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Caregivers play an essential role in the recovery of their adult loved ones with serious mental illness (SMI). Promoting caregiver empowerment and well-being is critical but has often been overlooked. Family peer interventions are well-suited to fill this need; however, research is limited supporting their use with caregivers of adults with SMI. Our team is currently engaged in a study evaluating an adapted version of the evidenced-based Parent Connectors program^1,2, renamed Family Connectors (FC), for caregivers of young adults recently discharged from the First Episode Psychosis program in New York (OnTrackNY). This paper, written collaboratively with family peer professionals, describes the adaptation process we followed to systematically document the family peer professional experience one year into delivering the FC program to this novel population. Modifications made to improve intervention fit included tailoring the content of the intervention, incorporating an outside approach into the program, lengthening the service in some cases, and adding a weekly peer supervision meeting. We hope that these insights are used to inform future efforts to advance support for families of loved ones with SMI, and more broadly, that our approach serves as a model for effective collaboration to improve the application of peer support services for unique groups.

BACKGROUND:Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels. METHODS:Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category. RESULTS: = 0.03). No associations were observed among non-OWOB participants. CONCLUSIONS:Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development.

Previous research has demonstrated a critical link between maternal mental health and infant development. However, there is limited understanding of the role of autonomic regulation in postpartum maternal mental health and infant outcomes. In the current study, we tested 76 mother-infant dyads from diverse socioeconomic backgrounds when infants were 3-months of age. We recorded simultaneous ECG from dyads while baseline EEG was collected from the infant; ECG heart rate variability (HRV) and EEG theta-beta ratio and alpha asymmetry were calculated. Dyadic physiological synchrony was also analyzed to better understand the role of autonomic co-regulation. Results demonstrated that lower maternal HRV was associated with higher self-reported maternal depression and anxiety. Additionally, mothers with lower HRV had infants with lower HRV. Maternal HRV was also associated with higher infant theta-beta ratios, but not alpha asymmetry. Exploratory analyses suggested that for mother-infant dyads with greater physiological synchrony, higher maternal HRV predicted increased infant theta-beta ratio via infant HRV. These findings support a model in which maternal mental health may influence infant neurophysiology via alterations in autonomic stress regulation and dyadic physiological co-regulation.

Patients with hypoplastic left heart syndrome (HLHS) and its variants rely on the right ventricle (RV) to provide cardiac output. Diminished RV systolic function has been associated with poor clinical outcomes in this population. Echocardiographic strain has emerged as a useful method to quantify RV deformation. We aimed to describe fetal strain in the systemic RV and further investigate if there was any correlation with clinical outcomes. We conducted a retrospective, single center study evaluating strain in fetuses with systemic RV. We measured fetal RV global longitudinal strain (GLS) and segmental strain using Tomtec 2D speckle tracking software and compared these findings to controls. Fifty patients with systemic RV were included in the study group with controls matched one to one for each echocardiogram. Ten patients died after first-stage palliation. GLS was reproducible, with interobserver ICC 0.82. There was no statistically significant difference in GLS among different HLHS subtypes. Abnormal GLS did not correlate with worse clinical outcomes. GLS in systemic RVs in the 2nd and 3rd trimester did not vary significantly throughout gestation and did not correlate with clinical outcomes. Risk factors associated with poor outcome were mainly postnatal. Multi-centered studies are needed to determine if these findings hold true in a larger sample size.

We elucidated the molecular fingerprint of vulnerable excitatory neurons within select cortical lamina of individuals with Down syndrome (DS) for mechanistic understanding and therapeutic potential that also informs Alzheimer's disease (AD) pathophysiology. Frontal cortex (BA9) layer III (L3) and layer V (L5) pyramidal neurons were microisolated from postmortem human DS and age- and sex-matched controls (CTR) to interrogate differentially expressed genes (DEGs) and key biological pathways relevant to neurodegenerative programs. We identified > 2300 DEGs exhibiting convergent dysregulation of gene expression in both L3 and L5 pyramidal neurons in individuals with DS versus CTR subjects. DEGs included over 100 triplicated human chromosome 21 genes in L3 and L5 neurons, demonstrating a trisomic neuronal karyotype in both laminae. In addition, thousands of other DEGs were identified, indicating gene dysregulation is not limited to trisomic genes in the aged DS brain, which we postulate is relevant to AD pathobiology. Convergent L3 and L5 DEGs highlighted pertinent biological pathways and identified key pathway-associated targets likely underlying corticocortical neurodegeneration and related cognitive decline in individuals with DS. Select key DEGs were interrogated as potential hub genes driving dysregulation, namely the triplicated DEGs amyloid precursor protein (APP) and superoxide dismutase 1 (SOD1), along with key signaling DEGs including mitogen activated protein kinase 1 and 3 (MAPK1, MAPK3) and calcium calmodulin dependent protein kinase II alpha (CAMK2A), among others. Hub DEGs determined from multiple pathway analyses identified potential therapeutic candidates for amelioration of cortical neuron dysfunction and cognitive decline in DS with translational relevance to AD.

OBJECTIVE/UNASSIGNED:This study aimed to characterize the perceived priorities of state and county policy makers for youth mental health services and the factors that influence those priorities. METHODS/UNASSIGNED:Mental health agency officials (N=338; N=221 state officials, N=117 county officials) representing 49 states completed a Web-based survey in 2019-2020. On 5-point scales, respondents rated the extent to which 15 issues were priorities for their agency in providing youth mental health services and the extent to which nine factors influenced those priorities. RESULTS/UNASSIGNED:Suicide was identified as the highest priority (mean±SD rating=4.38±0.94), followed by adverse childhood experiences and childhood trauma and then increasing access to evidence-based treatments. Budget issues (mean=4.27±0.92) and state legislative priorities (mean=4.01±0.99) were perceived as having the greatest influence on setting priorities. CONCLUSIONS/UNASSIGNED:These findings provide insights into youth mental health policy priorities and can be used to guide implementation and dissemination strategies for research and program development within state and county systems.

Health care transition (HCT) is the process of changing from a pediatric to an adult model of care. Young adult pediatric recipients of liver transplant transferring from pediatric to adult health care services are highly vulnerable and subject to poor long-term outcomes. Barriers to successful transition are multifaceted. A comprehensive HCT program should be initiated early in pediatrics and continued throughout young adulthood, even after transfer of care has been completed. It is critical that pediatric and adult liver transplant providers establish a partnership to optimize care for these patients. Adult providers must recognize the importance of HCT and the need to continue the transition process following transfer. While this continued focus on HCT is essential, current literature has primarily offered guidance for pediatric providers. This position paper outlines a framework with a sample set of tools for the implementation of a standardized, multidisciplinary approach to HCT for adult transplant providers utilizing "The Six Core Elements of HCT." To implement more effective strategies and work to improve long-term outcomes for young adult patients undergoing liver transplant, HCT must be mandated as a routine part of posttransplant care. Increased advocacy efforts with the additional backing and support of governing organizations are required to help facilitate these practices.