Recent animal and human studies suggest that mental stress may damage the brain. Reduced hippocampal volume has been reported in several cross-sectional studies of PTSD. Optimally, this phenomenon should be studied prospectively, by measuring brain structures in the same individuals prior to, or immediately following, the traumatic event, and again some time after the development of the disorder. The PI?s prospective study of hippocampal volume in PTSD performed at Hadassah University Hospital in Jerusalem, Israel (of which the proposed project represents a competing continuation) found that trauma survivors who developed PTSD did not differ from those who do not with regard to the volume of their hippocampi one week and six months after the traumatic event. These data refute a """"""""vulnerability"""""""" hypothesis, according to which smaller hippocampi represent a risk factor for PTSD upon traumatic exposure. However, these data do not definitively refute an """"""""acquisition"""""""" hypothesis, because damage to the hippocampus may take more than six months to develop. The main goal of this study is to extend the follow-up period of the previous study by re-evaluating hippocampal volume four years later and comparing these measurements with those obtained at one week. Additionally, the proposed study will evaluate the volume of the prefrontal lobe, which is a brain area that mediates attention and executive cognitive functions found to be impaired in PTSD. Prefrontal structural abnormalities have been reported in other mental disorders but have not yet been studied with regard to PTSD. The study will evaluate four-year post-trauma magnetic resonance (MR) images of the brain in subjects for whom one-week and six-month images are already available. These images will be subjected to volumetric analyses of hippocampus and prefrontal lobe at the Brigham and Women?s Hospital in Boston by the US co-PI, a leader in this field. The data will be tested regarding the """"""""acquisition"""""""" hypothesis for hippocampus, and the """"""""vulnerability"""""""" hypotheses for prefrontal lobe. Demonstrating pre-existing neuroanatomic risk factors, or progressive damage to the brain, in individuals with PTSD could have important implications for understanding the disorder, and for interventions aimed at preventing its transformation into a chronic, unremitting condition.
