White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event

•We investigated white matter integrity in a large medication-free PTSD population.•We included PTSD patients following a specific single traumatic event.•FA increase was noted in prefrontal cortex and corpus callosum in PTSD patients.Post-traumatic stress disorder (PTSD) is a serious and common psychiatric illness. Most previous diffusion tensor imaging (DTI) studies in PTSD have investigated white matter alterations in chronically ill and treated patients who experienced stressors variable in their intensity and duration. They also used non-traumatized individuals as controls, which makes it difficult to isolate PTSD-specific abnormalities from general stress effects. We describe a DTI study in a large drug-naive cohort of PTSD patients with the unique characteristics of a single-incident external trauma event, which offers a valuable opportunity for elucidating the core pathophysiology of PTSD. Our study showed that, relative to similarly stressed controls, PTSD patients had a significant fractional anisotropy increase, as well as axial and radial diffusivity alterations in the white matter beneath left dorsolateral prefrontal cortex and forceps major. Our findings help define clinically relevant PTSD-related white matter abnormalities in patients with a relatively short disease duration, suggesting that disruptions in dorsolateral prefrontal circuitry may be a contributing factor to fear-extinction deficits in PTSD.

Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.