The Biological Cost of External and Internal Resilience Factors in Trauma Survivors

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Over 70% of individuals world-wide have been exposed to at least one traumatic event and a significant subset will develop posttraumatic stress disorder (PTSD). The biological cost of trauma is evident in the excessive “wear and tear” on biological systems which can accelerate aging of neural and cellular processes. For example, the brains of individuals with PTSD appear 1-2 years older than same-aged counterparts without PTSD. Trauma exposure also modifies gene expression through the accumulation of DNA methylation. DNA methylation levels increase with chronological age but this “epigenetic clock” is accelerated by traumatic events. Despite these negative effects, the majority of trauma-exposed individuals do not develop PTSD. Certain individual strengths or socioenvironmental resources increase the likelihood of overcoming the impact of trauma. These resilience factors may help buffer against trauma-related accelerated brain and epigenetic aging. However, there may be hidden biological costs associated with these factors, especially for individuals who experience more severe symptoms acutely post-trauma. This project tests whether, in trauma survivors, internal resources have a significantly higher biological cost compared to external resources. Using a large longitudinal dataset (the AURORA study) of traumatically injured individuals recruited from Emergency Departments across the United States, we will test the associations between external resilience (operationalized as higher income), internal resilience (operationalized as higher scores on the Connor-Davidson Resilience Scale), and accelerated brain (brainAGE; Aim 1) and epigenetic aging (epiAGE; Aim 2). We anticipate that brainAGE and epiAGE will mediate the relationship between resilience factors and future PTSD symptoms (6-months post-injury). Importantly, we anticipate an individual’s acute PTSD symptoms (2-weeks post-injury) will moderate these relationships. Participants with more severe 2-week PTSD symptoms and higher internal resilience will show greater brainAGE and epiAGE whereas participants with similar symptoms and higher external resilience will display more typical aging patterns. In Aim 3, we will test the relationship between brainAGE, PTSD, and resilience factors in a South African cohort of women with recurrent trauma exposure to evaluate generalizability. The training goals of this fellowship were designed to further the applicant’s knowledge and skills in: 1) advanced neuroimaging analyses, 2) epigenomic approaches for neuropsychiatric research, 3) clinical understanding of PTSD, 4) cultural competency in epidemiologic psychiatric research, and 5) scientific communication and effective mentorship. These results will inform the treatment and prevention of PTSD. By better understanding how resiliency is promoted biologically, pharmacological therapeutics may be developed that boost the endogenous resilience mechanisms. In addition, the findings may improve post-trauma interventions at a public health level by illustrating the types of resilience factors that clinicians and policy makers should target.