Twin Study of Biologic Markers for PTSD

PI: Lisa Shin
Project Number: 5R01MH054636
Project Dates: 6/1/2012-10/31/2014

This competing continuation proposal will take advantage of a unique opportunity to further follow up on a series of investigations of the origin of biologic markers for post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The main possible marker origins to be addressed are: a.) familial vulnerability for PTSD vs. b.) acquired PTSD sign. Familial vulnerability will be evaluated by examining the main effect of between-pair Diagnosis (PTSD vs. non- PTSD in the combat-exposed twin), as well as by contrasting the (high-risk) combat-unexposed co-twins of combat-exposed twins with PTSD vs. the (low-risk) combat-unexposed co-twins of combat-exposed twins without PTSD. Acquired PTSD sign will be evaluated by examining the interaction between Diagnosis and within-pair Exposure (combat vs. no combat), as well as by contrasting the PTSD combat twins vs. their own combat-unexposed co-twins.

Recent pilot data suggest that the following may be familial vulnerability factors for PTSD: a.) decreased rostral anterior cingulate cortex (rACC) and increased amygdala activation during passive viewing of overt fearful facial expressions during fMRI, and b.) increased dorsal ACC activation during a multi-source interference task (MSIT) during fMRI. In contrast, pilot data suggest that c.) impaired retention of extinction of a psychophysiologic conditioned fear response may be an acquired PTSD sign. The work in this competing continuation proposal will include testing the above three pilot findings in additional twin subjects in an attempt to obtain definitive results. Finding (c) will also be pursued using fMRI. Additional experiments will include measuring d.) regional cerebral blood flow during script-driven imagery of combat and other personal stressful events during positron emission tomography, and e.) n- acetyl aspartate levels in dACC, rACC, ventromedial prefrontal cortex, and hippocampus by magnetic resonance spectroscopy. Twin subjects will be invited travel to the Massachusetts General Hospital for two days of neuroimaging protocols. 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. Additionally the proposed research may identify biologic mediators of the effects of candidate genes on risk for PTSD.