This project will take advantage of the unique opportunity to follow up a successful investigation of the origin of elevated responses to sudden, loud tones in post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The proposed study will evaluate the origin of two additional putative PTSD biologic markers that reflect amygdala hyper (re)activity in PTSD. The possible marker origins to be addressed are: a.) Familial vulnerability for PTSD, vs. b.) acquired PTSD sign. Familial vulnerability will be evaluated by comparing the (high-risk) non-combat-exposed co-twins of combat-exposed twins with PTSD vs. the (low-risk) non-combat-exposed co-twins of combat-exposed twins without PTSD. Acquired PTSD sign will be evaluated by examining the interaction between a between-pair PTSD Diagnostic status factor PTSD vs. non-PTSD in the combat-exposed twin) and a within-pair Exposure factor (combat vs. non-combat). Dependent variables (markers) will include a.) Strength of acquisition and extinction of a classically conditioned differential skin conductance response, i.e., "conditionability," and b.) functional magnetic resonance imaging (fMRI) amygdala response to "masked" presentations of fearful facial expressions. Each marker is non-invasive; can be measured on an ambulatory basis; has been shown in previous, published, peer-reviewed research to significantly differentiate PTSD and non-PTSD subject groups; and is capable of being informed by the data to be obtained in the proposed project. Twin subject pairs will travel to the Massachusetts General Hospital for a long weekend to undergo psychodiagnostic and psychometric evaluation, and the conditionability and fMRI masked faces procedures. Statistical significance will be tested by means of analyses of variance and covariance, a priori t-tests, and correlational analyses. Results are expected to advance our understanding of the constitutional vs. acquired nature of biologic abnormalities in PTSD and the neuroanatomy and pathogenesis of this disorder. Results may also have implications for the prophylactic screening of persons at high risk for the development of PTSD upon exposure to military combat or other severe stressors.