Twin Study of Biologic Markers for PTSD

Massachusetts General Hospital, Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): This supplementary project will take advantage of a unique opportunity to add an important neuroimaging study to an ongoing investigation of biologic abnormalities in post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The proposed study has two major objectives. The first is to test for group differences in resting cerebral metabolic activity in three regions of interest (ROIs), viz., amygdala, anterior cingulate cortex (ACC), and hippocampus, in Vietnam combat veterans with vs. without PTSD. ACC will be further subdivided into dorsal, rostral (pregenual), and ventral (subgenual/subcallosal) divisions. The second major objective is to evaluate the origin of any resting cerebral metabolic differences that are found. Two major possible origins will be tested: familial vulnerability factor for PTSD vs. acquired PTSD sign. The dependent variable will be resting regional cerebral metabolic rates for glucose (rCMRglu) as determined by 18F-fluorodeoxyglucose positron emission tomography (PET FDG). PET images will be co-registered with structural magnetic resonance images (MRIs) on which the a priori ROIs will be morphometrically delineated. Twin subjects will already be participating in functional MRI and psychophysiology studies at the Massachusetts General Hospital, to which the PET FDG procedure will be added. Statistical significance will be tested by means of a mixed model that treats PTSD Diagnosis (i.e., combat-related PTSD vs. non-PTSD in the combat-exposed twin) as a between-pairs fixed effect, combat Exposure as a within-pair fixed effect, and twin pairs as a random effect, supplemented by planned Student's t-tests that specifically address the a priori hypotheses. In addition to the primary ROI analyses, statistical parametric mapping (SPM) will be performed in order to preserve the possibility of identifying significant effects in regions outside the a priori selected ROIs, and to evaluate the specificity of important findings in any of the project's ROIs. Results are expected to advance our understanding of the constitutional vs. acquired nature of neurophysiologic abnormalities in PTSD and the pathogenesis of this disorder. Results may also have implications for the screening of persons at high risk for the development of PTSD upon exposure to military combat or other severe stressors. [unreadable] [unreadable]