Epigenetic susceptibility of behavioral and addictive disorders during pre/pubescence after natural disaster exposures in-utero

点击翻译按钮获取中文摘要

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.