Psychosocial unpredictability during pregnancy and offspring neurodevelopment: Uncovering mechanisms and sensitive windows in utero - PROJECT SUMMARY/ABSTRACT My career goal is to build a translational program of research that investigates the developmental origins of psychiatric disease, with a focus on perinatal mechanisms by which adversity can be transmitted from parents to their children. To date, I have obtained extensive training in the assessment of adversity and psychiatric symptomatology in historically minoritized families, maternal-infant cortisol functioning, infant fMRI, and perinatal mental health. My career development plan builds on this knowledge base by providing crucial, intensive training in the imaging and analysis of fetal brain networks, ecological momentary assessment, advanced longitudinal statistics, and fetal ECG. Completion of the proposed research and training is essential to prepare me to lead a lab that leverages multimodal developmental neuroscience techniques to discover risk and resilience processes during the earliest stages of life, which may help to disrupt the intergenerational transmission of health disparities. Research Project: Exposure to maternal stress during pregnancy is one of the most robust transdiagnostic risk factors for psychiatric illness across the lifespan. Yet we lack critical information about the features of stress that are most salient for fetal biology, the intrauterine mechanisms that link maternal stress to child psychiatric risk, and whether there are sensitive windows when fetal biology is most strongly impacted by maternal stress. Using a multimodal approach, the goal of this K99/R00 is to examine intraindividual variation in maternal prenatal stress as a unique predictor of two candidate mechanisms underlying psychiatric risk in children: fetal autonomic nervous system (ANS) development and fetal functional neurocircuitry. In the K99 portion of this award, we will leverage a repeated measures longitudinal design to examine associations between real-world variation in maternal stress and fetal ANS development across 14 weeks of pregnancy, including examination of sensitive windows (Aim 1). We will also examine how intraindividual variation in maternal stress relates to long-term trajectory of fetal ANS development and fetal neurocircuitry, predicting that stress unpredictability will uniquely impact fetal neurodevelopment (Aim 2). The R00 project will provide necessary context to this neuromaturational model by evaluating how interactions across stress-responsive systems (HPA axis and ANS) and maternal history of lifetime adversity modulate stress-related programming of the fetal brain in a high-risk cohort. In the R00, we will additionally assess whether adversity-related signatures in the fetal brain persist into infancy (Aim 3). This line of research has potential to isolate the beginning of developmental cascades that underscore emergence of depression and other psychiatric disorders, thus informing interventions that can leverage the unparalleled plasticity of the developing brain.
