White matter abnormalities associated with military PTSD in the context of blast TBI

Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common among recent military veterans and involve substantial symptom overlap, making clinical distinction and effective intervention difficult. Emerging evidence of cerebral white matter abnormalities associated with mTBI may provide a biological measure to inform diagnosis and treatment, but the potentially confounding effects between PTSD and mTBI have largely gone unexamined. We collected diffusion imaging data from 133 recently-deployed American service members who developed PTSD and/or sustained mTBI, or had neither condition. Effects of PTSD and mTBI on traditional tensor-based measures of cerebral white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were compared in anatomical regions of interest and individual voxels throughout the brain. Generalized FA (GFA), which allows for multiple fiber orientations per voxel, was also included to improve sensitivity in white matter areas containing crossing or diverging axon bundles. PTSD was consistently associated with high GFA in select brain regions, greater likelihood of regions and voxels with abnormally low MD, and a greater number of voxels with abnormally high FA, while mTBI was associated with fewer high MD regions. Overall, PTSD was associated with more restricted diffusion (low MD) and greater anisotropy (high GFA) in regions of crossing/diverging fibers poorly characterized by a single tensor (FA), suggesting that interstitial fibers may be involved. Contrary to earlier results in a sample without PTSD, mTBI was not associated with anisotropy abnormalities, perhaps indicating the cooccurrence of PTSD and mTBI requires special consideration with regard to structural brain connectivity.