Summary/Abstract: The risk for developing future psychiatric and addiction disorders starts early in life, with
evidence emphasizing the critical contribution of the in utero environment. Maternal psychosocial stress has a
significant impact on the prenatal environment and contributes to negative health and neurobehavioral outcomes in
offspring. Our research (Stress in Pregnancy, SIP study), along with that of others, has shown that in utero exposure
to maternal psychosocial stress is a major predictor of the risk for fear-related and impulse control-related problems
during early childhood. We are now well positioned to conduct a long-term follow-up of our unique racially and
financially diverse SIP study population to identify biomarkers of children’s behavior and physiological reactivity
relevant for future subsequent behavioral disorders and addictive risk. Despite its importance, few studies have
investigated placental molecular signatures to bio-behavioral assessments from early life through the pre/pubertal
phase. Exploiting the SIP study's bio-repositories and deep-phenotyped child behaviors, our preliminary results show
that epigenetic changes of the hypothalamic-pituitary-adrenal (HPA) axis and immune systems are associated with
fear, anxiety, and emotion dysregulation among children exposed to in utero maternal stress. The SIP study cohort
has many strengths: its consistent long-term follow-up, from in utero, its diversity (financially and racially), its
extensive repository of stored biospecimens (placenta, toenail, hair samples), and its quasi-experimental design.
The cohort is now entering pre/puberty (ages 9-13), a time for rapid social and biological transition and a peak time
for the emergence of maladaptive, risk-taking behaviors with the brain still developing cognitive functions. Using
this unparalleled opportunity, we will follow the cohort to 1) examine the role of exposure to SS in utero along with
the effect of postnatal stress (normative stress, parenting) on neurodevelopmental functioning, as measured by
multiple behavioral, physiological, and neuropsychological assessments; 2) determine the relationship between
the prenatal epigenome signature in the placenta (along with an a priori focus on the HPA-axis and immune network
genes) on the subsequent risk for negative behavioral characteristics (i.e., excessive anxiety and disruptive
behaviors) and impaired executive functioning, known to elevate the risk for early initiation of substance use.
Following our prior work, we will also examine sex-specific manifestations of the behavioral phenotypes (more
internalizing problems in girls and externalizing in boys). We will further explore the moderating role of
socioeconomic status when intersecting with prenatal SS-stress and postnatal stress on individual differences in
cognitive neuro-behaviors, which make pre/pubescent children more vulnerable for a subsequent onset of
behavioral and addictive disorders. We will build on our unique repository of stored biospecimens and profile
chromatin accessibility across the epigenome and RNA expression network in the placenta. Given the steeply
increasing incidence of adverse stressors, especially natural disasters (e.g., hurricanes, wildfires and pandemics),
investigation of the short- and long-term impact of SS-stress on neurodevelopment from in utero through
pre/puberty, will help us to identify problems and potentially lead to significant interventions for mother and child.
