GTP Grady Trauma ProjectProject Overview
Genetic and Trauma-Related Risk Factors for PTSD
at Grady Memorial HospitalThis project aims to determine the relative contribution of genetic and trauma-related risk factors for Posttraumatic Stress Disorder (PTSD) in a cross-sectional study of a highly traumatized, low socioeconomic status, minority urban population. Although some level of fear and stress is normal following a traumatic experience, understanding the etiology of PTSD requires knowing why chronic pathological symptoms do not occur in all who experience trauma. Individuals appear to have different vulnerabilities for subsequent response to traumatic stress. It is now commonly accepted that PTSD results from an interaction of predisposing genetic and environmental risks that enhance the likelihood of a pathological stress response and fear memory following severe trauma. However, almost nothing is known of the nature of the genetic contribution(s) and how they interact with other risk factors We will examine 1300 non-psychiatric patients from the General Medical Clinic at Grady Memorial Hospital in Atlanta . Our pilot data suggests that over 80% of this population has suffered significant trauma and approximately 30% have PTSD. We will examine three independent factors that contribute to the relative risk for PTSD following trauma: genotype polymorphism, lifetime history of trauma, and peri-traumatic emotional response to the PTSD-related event. Genetic risk factors include described polymorphisms that have been shown to contribute to the development of psychopathology in other stress-related psychiatric disorders, including monoamine related genes (5HTT, DBH, DAT, and COMT), brain-derived neurotrophic factor (BDNF), and genes involved in HPA axis regulation ( GR, CRF-R1, FKBP5 ) . Lifetime history of trauma includes childhood trauma and total lifetime trauma. Emotional response to the trauma includes subjective trauma severity as well as peri-traumatic dissociation. Covariates that will be examined include family psychiatric history, substance abuse and dependence, and comorbid psychiatric diagnoses. The primary dependent variables include presence or absence of PTSD diagnosis and PTSD severity. By examining identified candidate genes, known trauma history risk factors, and PTSD diagnosis as well as its component traits, this study will further the understanding of PTSD. Through a greater understanding of the vulnerability factors, both genetic and environmental, that contribute to pathological fear and stress following a trauma, this work will further the development of model systems as well as potentially provide novel intervention, diagnostic, and treatment approaches for this debilitating disorder.
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