Abstract
Posttraumatic stress disorder (PTSD) is known to persist, eliciting early medical co-morbidity, and accelerated aging. Although PTSD diagnosis has been found to be associated with smaller volume in multiple brain regions, posttraumatic stress (PTS) symptoms and their associations with brain morphometry are rarely assessed over long periods of time. We predicted that persistent PTS symptoms across ~24 years would be inversely associated with hippocampal, amygdala, anterior cingulate volumes, and hippocampal occupancy (HOC = hippocampal volume/[hippocampal volume + inferior lateral ventricle volume]) in late middle age. Exploratory analyses examined prefrontal regions. We assessed PTS symptoms in 247 men at average ages 38 (time 1) and 62 (time 2). All were trauma-exposed prior to time 1. Brain volumes were assessed at time 2 using 3 T structural magnetic resonance imaging. Symptoms were correlated over time (r = 0.46 p < .0001). Higher PTS symptoms averaged over time and symptoms at time 1 were both associated with lower hippocampal, amygdala, rostral middle frontal gyrus (MFG), and medial orbitofrontal cortex (OFC) volumes, and a lower HOC ratio at time 2. Increased PTS symptomatology from time 1 to time 2 was associated with smaller hippocampal volume. Results for hippocampal, rostral MFG and medial OFC remained significant after omitting individuals above the threshold for PTSD diagnosis. Even at sub-diagnostic threshold levels, PTS symptoms were present decades after trauma exposure in parallel with highly correlated structural deficits in brain regions regulating stress responsivity and adaptation.
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Content of this manuscript is the responsibility of the authors and does not represent official views of the National Institutes of Health, or the Veterans’ Administration. This work is supported by grants from the National Institute on Aging at the National Institutes of Health [R01 AG050595, R01 AG022381 and an R25 AG043364 training grant]. U.S. Department of Veterans Affairs, Department of Defense; National Personnel Records Center, National Archives and Records Administration; Internal Revenue Service; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University provided invaluable assistance in the conduct of the VET Registry. The authors gratefully acknowledge the continued cooperation of the research participants and the dedicated efforts of many staff members.
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L.K. McEvoy has stock options in CorTechs Laboratories, Inc. A.M. Dale is a founder of and holds equity in CorTechs Laboratories, Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by University of California, San Diego in accordance with its conflict of interest policies.
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Franz, C.E., Hatton, S.N., Hauger, R.L. et al. Posttraumatic stress symptom persistence across 24 years: association with brain structures. Brain Imaging and Behavior 14, 1208–1220 (2020). https://doi.org/10.1007/s11682-019-00059-x
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DOI: https://doi.org/10.1007/s11682-019-00059-x