Epigenomic Predictors of PTSD and Traumatic Stress in an African American Cohort

PROJECT SUMMARY Post-traumatic stress disorder (PTSD) is a debilitating stress-related mental disorder that significantly impacts African Americans (AAs). Our earlier work identified key adversity factors, including cumulative trauma, emotional maltreatment and financial difficulties that, in combination with DNA methylation in glucocorticoid receptor regulatory network genes, prospectively predicted PTSD symptom severity. While studies examining the risk of PTSD among white and AA populations have shown that AAs are at a higher risk of PTSD following traumatic exposure, there are few studies that have specifically examined the contextual factors that lead to differential risk within AA populations. Within-population studies have the potential to uncover social and environmental factors that ultimately lead to differences in PTSD risk. Indeed, psychosocial and environmental mechanisms, such as living in unsafe environments and exposure to differing levels of social support, may contribute to differential PTSD risk in AAs. Our prior research confirms these findings. What remains unknown, however, are: (i) the potential buffering effects of positive psychosocial exposures, such as social support and cohesion, which have been shown to play an important role in mitigating risk of PTSD; and (ii) the extent to which peripheral epigenetic measures are relevant to the target organ of PTSD—the brain. Advances in the science of linking peripheral epigenomic variation to central nervous system (CNS) epigenomic variation (herein called brain-related epigenomic variation) are urgently needed in order to gain deeper mechanistic insight into PTSD-related health gaps among AAs affected by this mental health condition. Therefore, the overall goal of this renewal application is to provide mechanistic insight into how contextual factors, both positive and negative, affects brain-related epigenomic variation to impact risk of PTSD and traumatic stress in a prospective, community-based cohort of AAs. To achieve this goal, we will leverage publicly available, multi-tissue datasets to identify epigenomic markers that are highly correlated in brain and blood, and focus our proposed analyses on these correlated measures using existing and newly collected epigenomic and gene expression data from the Detroit Neighborhood Health Study (DNHS) cohort. The genomic data will be paired with DNHS survey data, which includes annual measures of adversity, psychopathology, and social support and cohesion. We will focus analyses on adversities previously implicated in our earlier work (e.g. cumulative trauma, financial difficulties, emotional mistreatment) and positive psychosocial exposures previously implicated in PTSD (social support and neighborhood social cohesion). Results from this study will provide a deeper characterization of how psychosocial exposures, both positive and negative, influence brain-related epigenomic processes to impact stress-related psychopathology among AAs, an under-studied U.S. population with substantial health gaps in traumatic-stress related psychopathology.