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

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PROJECT SUMMARY Post-traumatic stress disorder (PTSD) is a debilitating stress-related mental disorder that disproportionately impacts African Americans (AAs). Our earlier work identified key social adversity factors, including loneliness, perceived discrimination, 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 socioenvironmental factors that lead to differential risk within AA populations. Within-population studies have the potential to uncover exposures that ultimately lead to race/ethnic disparities in PTSD risk. Indeed, structural, psychosocial and environmental mechanisms, such as living in unsafe environments and exposure to discrimination, 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 social 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) is urgently needed in order to gain deeper mechanistic insight into PTSD-related health disparities among AAs affected by this mental health condition. Therefore, the overall goal of this renewal application is to provide mechanistic insight into how social context, 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 social adversity, psychopathology, and social support and cohesion. We will focus analyses on social adversities previously implicated in our earlier work (loneliness, perceived discrimination, cumulative trauma, financial difficulties, emotional mistreatment) and positive social exposures previously implicated in PTSD (social support and neighborhood social cohesion). Results from this study will provide a deeper characterization of how social exposures, both positive and negative, influence brain-related epigenomic processes to impact stress-related psychopathology among AAs, an under-studied U.S. minority group with substantial health disparities in traumatic-stress related psychopathology.