Self-reported Fatigue was Associated with Increased White-matter Alterations in Long-term Traumatic Brain Injury and Posttraumatic Stress Disorder Patients

is a long-lasting problem in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), with limited research that investigated the fatigue-related white-matter changes within TBI and/or PTSD cohorts. This exploratory cross-sectional study used diffusion tensor imaging (DTI) and neuropsychological data collected from 153 male Vietnam War veterans, as part of the Alzheimer's Disease Neuroimaging Initiative -Department of Defense, and were divided clinically into control veterans, PTSD, TBI, and with both TBI and PTSD (TBI + PTSD). The existence of fatigue was defined by the question Do you often feel tired, fatigued, or sleepy during the daytime?. DTI data were compared between fatigue and non-fatigue subgroups in each clinical group using tract-based spatial statistics voxel-based differences. Fatigue was reported in controls (29.55%), slightly higher in TBI (52.17%, PBenf = 0.06), and significantly higher in both TBI + PTSD (66.67%, PBenf = 0.001) and PTSD groups (79.25%, PBenf < 0.001). Compared to non-fatigued subgroups, no white-matter differences were observed in the fatigued subgroups of control or TBI, while the fatigued PTSD subgroup only showed increased diffusivity measures (i.e., radial and axial), and the fatigued TBI + PTSD subgroup showed decreased fractional anisotropy and increased diffusivity measures (PFWE < 0.05). The results act as preliminary findings suggesting fatigue to be significantly reported in TBI + PTSD and PTSD decades post-trauma with a possible link to white-matter microstructural differences in both PTSD and TBI + PTSD. Future studies with larger cohorts and detailed fatigue assessments would be required to identify the white-matter changes associated with fatigue in these cohorts.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

Fatigue is a long-lasting problem in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), with limited research on its underlying white-matter changes. This study used diffusion tensor imaging (DTI) and neuropsychological data from Vietnam War veterans to explore the relationship between fatigue and white-matter differences in TBI and/or PTSD cohorts. Fatigue was significantly reported in TBI + PTSD and PTSD groups, and was associated with increased diffusivity measures in the fatigued PTSD subgroup and decreased fractional anisotropy and increased diffusivity measures in the fatigued TBI + PTSD subgroup. Further studies with larger cohorts are needed to understand the white-matter changes associated with fatigue in these populations.