Clinical and biologic health trajectories after early life adversity

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Project Summary/Abstract This career development award details a 5-year training plan to facilitate the transition of Dr. Barbara H. Chaiyachati to an independent career as a physician-scientist studying predictors of mental and physical health of children after trauma with an objective to identify actionable targets of intervention. Experiences of child abuse and neglect place hundreds of thousands of children at risk for negative health outcomes every year in the U.S. Better understanding of proximate mental and physical health predictors after childhood traumatic stressful events (TSE), including predictive role of genetic susceptibility integrated with early biologic embedding by epigenetic age acceleration (EAA) and increased inflammation, may facilitate targeted interventions to ameliorate the spectrum of long-term health burdens. Thus, multimodal phenomic and genomic approaches are needed to elucidate the complex connections between maltreatment and health. The proposed project builds on the diverse clinical and research experiences of the candidate, with mentorship led by Dr. Raquel Gur, the Karl and Linda Rickels Professor of Psychiatry, Neurology and Radiology at the University of Pennsylvania and an expert in neurodevelopmental trajectories, and Dr. Hakon Hakonarson, Professor of Pediatrics at the Children’s Hospital of Philadelphia and an expert in translational genomics. A team of collaborators adds expertise in developmental psychology, basic and clinical immunology, psychiatric genetics, and behavioral epigenomics, with grounding in child abuse clinical care. The research leverages large, ancestry-diverse, adversity-exposed cohorts within established biorepositories to identify measurable, biologically-relevant health predictors after adversity in childhood. Dr. Chaiyachati will conduct phenomic (physical, mental health, systemic inflammation by cytokines) and genomic (whole genome and methylome) assessments. Specifically, Aim 1 is to determine the impact of TSEs and genetic stress sensitivity, as marked by genetic risk for PTSD, on mental and physical health in adolescence; Aim 2 will assess the impact of TSE on epigenetic aging per DNA methylation clocks; and Aim 3 will test for increased inflammation after experiences of maltreatment. Completion of the proposed studies will improve our understanding of mental and physical health trajectories after experiences of trauma. This proposal will also provide the candidate with experience studying phenomic and genomic data, writing grants and scientific papers, and allow her to gain skills requisite for supervision and leadership. Furthermore, this proposal will establish Dr. Chaiyachati’s intersectional research agenda and position her for independence as a physician-scientist.