The STRONG STAR Multidisciplinary PTSD Research Consortium
Final rept. 1 Sep 2008-31 Aug 2014
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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Traumatic stress is a requirement for the development of PTSD. However, the majority of trauma-exposed persons do not develop PTSD. Therefore, examination of the typical effects of a stressor may not identify the critical components of PTSD risk or pathogenesis. One obvious explanation for individual differences in vulnerability to PTSD is that there may be genetic predisposition to susceptibility to precipitating stressors. However, to date, very few genetic polymorphisms for PTSD have been identified. An alternative mechanism that would impart lifelong vulnerability to PTSD is stable alterations in gene expression programmed by exposure to early life stressors. Therefore, the hypothesis to be addressed by this project is that early life exposure to stress or glucocorticoids programs a distinct neurochemical and behavioral phenotype during adulthood characterized by vulnerability to stressors that trigger PTSD. Moreover, we hypothesize that the susceptibility to PTSD can be reversed in adult offspring by anti-depressants which have been reported to reverse the epigenetic changes in expression of selected genes caused by stress. To address this hypothesis, the following specific aims are proposed 1. To generate and characterize models of early life stress. 2. To determine adult predictors of vulnerability to stress as determined by behavioral, physiological, and molecular and neurochemical measures. 3. To determine adult vulnerability to stress Adult offspring from models developed in Specific Aim 1 are exposed to a model of traumatic stress and then a fear conditioning paradigm. Behavioral, physiological and molecular neurochemical measures are made. 4. To determine the effects of treatment with the SSRI sertraline.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research