Posttraumatic stress symptom persistence across 24 years: association with brain structures

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.