Epigenetic Mechanisms of Post-traumatic Stress and Depression After Sexual Assault
More than 40 million Americans each year present to US emergency departments (EDs) for evaluation after trauma exposure. Posttraumatic stress disorder (PTSD) and posttraumatic major depression (PMD) are common, morbid outcomes among trauma-exposed survivors that greatly reduce mental and physical health. Posttraumatic interventions to prevent PTSD and PMD are very limited, because the molecular underpinnings of these outcomes remain poorly understood.
Need/Problem: National surveys indicate that 1 in 5 adult US women are sexually assaulted during their lifetime. Posttraumatic stress disorder (PTSD) and posttraumatic major depression (PMD) are common, morbid outcomes among adult women sexual assault (SA) survivors that greatly reduce mental and physical health. Posttraumatic interventions to prevent PTSD and PMD after SA are very limited, because the molecular underpinnings of these outcomes remain poorly understood.
Grant Summary: The project will combine the study of DNA collected from the largest longiduinal cohort of trauma-exposed individuals ever performed (n = 5,000) and from in vitro models of human cells treated with stress hormones (cortisol) to uncover epigenetic mechanisms (related to DNA methylation) that influence vulnerability for the development of PTSD and PMD.
Goals and Projected Outcomes: The study will establish new lines of translational research benefiting trauma survivors with the ultimate goal to gain important new mechanistic insights into PTSD and PMD development. Gaining such insights can have major implications by identifying predictive biomarkers and novel prevention and treatment candidates for these devastating disorders.
Dr. Anthony Zannas, MD, MSc, Ph.D.
Grant Details: The influence of DNA methylation differences at the time of SA on subsequent development of PTSD and PMD has never been assessed. In the present study, DNA has been collected from blood of SA survivors in the immediate aftermath of trauma, and life history and PTSD and PMD outcomes have been assessed at 1 and 6 weeks and at 6 and 12 months. The study of DNA methylation, an epigenetic modification that is affected by trauma exposure and can in turn influence gene and cell function, provides a valuable method to discover possible biomarkers that predict PTSD and PMD after SA and, importantly, to gain new biological insights based on these discoveries. After identifying the predictive genomic sites, we will mechanistically dissect the SA-related epigenetic signatures by using in vitro models of human immune cells treated with cortisol in conditions that mimic in vivo stress exposure. We will focus on DNA methylation at genomic sites that influence biological functions implicated in stress-related disorders: hypothalamic-pituitary-adrenal axis activity and immune function.