In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients' trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs—both the trauma-exposed and unexposed members—had significantly smaller hippocampi than non-PTSD pairs.
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This work was supported by Department of Veterans Affairs Merit Review Grants (to M.W.G. and S.P.O.), USPHS Grant R01-MH54636 (to R.K.P.) and USPHS Grant K02-MH01110 (to M.E.S.). The authors would like to thank M. Macklin, K. Sheldon, S. Williston, L. Paulus, H. Croteau and the VA Cooperative Studies VET Registry (M.E. Vitek, K. Bukowski, R. Havlicek, T. Colton, W.E. Nance, R.S. Paffenbarger, Jr., M.M. Weissman and R.R. Williams) for their assistance. We gratefully acknowledge the participation of the veterans of the VET Registry and the non-Registry twin participants.
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