Summary/Abstract: Accumulating evidence, including our own, indicates that in utero exposure to psychosocial
stress is associated with risks for elevated anxiety (ANX) and disruptive behavior (DB) symptomatology. In this
application, we will build on our existing birth cohort of children exposed and unexposed to Superstorm Sandy (SS)
in utero. SS randomly “assigned” stressful conditions to pregnant women and their offspring in our cohort, giving
us a unique opportunity to conduct a quasi-experiment of in utero stress. Using our deeply phenotyped cohort, we
propose to investigate whether in utero SS exposure modulates the impact of the postnatal stressful environment,
either amplifying (double-hit acceleration model) or shielding (stress inoculation model) the effects of postnatal
stress on ANX and DB symptomatology. We will continue to measure different types of postnatal stress (normative,
poor parenting, and COVID-related) to examine if magnitude, nature, timing and duration of the postnatal stressors
influences the direction and impact on such symptomatology. As well as the DSM-based diagnostic outcomes, we
will utilize the NIMH RDoC and focus on Negative Valence and Cognitive Control Systems (NVS/CCS), which will
enable a transdiagnostic perspective of pre- and postnatal stress-related changes in behavior and the brain.
Following our prior work, we will also examine sex-specific manifestations of the behavioral phenotypes (more
internalizing problems in girls and more externalizing in boys) and explore the moderating role of SES when
intersecting with individual differences in behaviors. As the brain is the central modulatory organ of
stress/adaptation and regulation, we will use neuroimaging to assess changes in brain structure, function, and
connectivity in limbic-frontal circuitry during early pre- and post-puberty, using a subsample of our cohort. Our
cohort was followed from in utero, with completed follow-up assessments (neurobehavioral, clinical, and biological
specimens), which will continue as they enter pre/puberty (ages 9-13), a time of peak risks for such problems and
sex-dimorphism. Specifically, we will: 1) examine the effects of SS-related stress and the postnatal psychosocial
environment on trajectories of clinical and adaptive neurobehaviors; 2) study the impact of prenatal SS stress and
postnatal stress on NVS/CCS brain outcomes (structure and function) and evaluate the extent to which NVS/CCS
structural changes mediate between prenatal SS-exposure and child anxiety and DB symptoms; and 3) develop
predictive models for NVS/CCS outcomes in early adolescence based on biological and behavioral measures
obtained in utero and/or the first decade of the child’s life. As pre/puberty is an important period of developmental
transition and heightened risk for ANX and DB, we will build on our unique repository of both clinical and stored
hair samples and continue to chart children’s neurobehavioral development and risk for psychopathology through
ages 9-13. Together with the inclusion of neuroimaging to investigate neural mechanisms centered on the
NVS/CCS and using tasks from the ABCD study, our study is uniquely positioned to elucidate the mechanisms of
fetal programing and threat sensitivity in the NVS/SSV that modulate the risks for anxiety and reactive aggression.
