Mount Sinai ECHO site for Perinatal Environment and Development Studies

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Although a range of prenatal exposures have been linked to adverse neurodevelopmental outcomes, associations with early neurobehavioral factors related to lifetime psychopathology risk are less well studied. Internalizing problems, most notably anxiety and depressive disorders, affect >400 million people globally with a sharp rise in these disorders in childhood and during/after the transition to adolescence. Identifying early risk and resiliency factors for internalizing disorders is critical to designing and implementing effective interventions to lessen their health burden. Interactions among environment, genes, sex, and life stage influence normal and maladaptive development. Starting in utero, the central nervous system (CNS) develops sequentially, with specific processes and network components of distinct functional domains (e.g., attention, emotion regulation) developing in a timed order; thus, effects of toxins depend on exposure timing as well as dose. Sex-specific effects also exist. Moreover, pregnant women and children are exposed to complex mixtures of chemicals as well as social stressors that co-vary and interact with each other. Differences in exposures in part drive health inequities because toxic environmental factors are not randomly distributed, but are often concentrated in segregated communities of color. The complexity in environmental neuroprogramming has not been fully assessed due to a lack of sufficiently large populations with the requisite longitudinal assessments, biosampling, and population diversity that would enable joint consideration of a number of environmental determinants through a developmental health equity lens. Herein, we expand our site's work with the national ECHO program to elucidate the role of complex mixtures (ambient air pollutants (APs), metals, stress, and nutritional exposures) starting in utero, in the programming of internalizing problems that emerge over childhood using a transdiagnostic framework. We will assess transdiagnostic (TD) dimensional features across select Research Domain Criteria (RDoC): (1) negative valence systems, (2) cognitive systems, and (3) arousal/regulation. We build upon methods our team developed via 3 awarded ECHO Opportunity for Infrastructure Funding (OIF) grants that will allow researchers to more fully capitalize on the large diverse sample, life course framework, and exposure data that ECHO provides. We will implement and disseminate methodological advances through collaborative ECHO science including: 1) satellite remote sensing AP models that reconstructpast exposure timing and dose; 2) novel high dimensional mixture statistics; 3) statistical methods to characterize windows of vulnerability and enhance power to detect complex interactions among chemicals, stress, nutrition and susceptibility factors (e.g., sex, race/ethnicity); and 4) methods to evaluate the combinability of ECHO cohort data to optimize discovery and replication. As the complex exposures considered herein also play a role in programming a number of health outcomes (e.g., perinatal, respiratory, obesity, positive health), our methods will be broadly applicable to the national ECHO program.