Characterizing White Matter Changes along Fibers in Treatment-Naive Pediatric Posttraumatic Stress Disorder

Children and adolescents are more susceptible than adults to developing posttraumatic stress disorder (PTSD). Pediatric PTSD is characterized by functional alterations in brain fear circuitry, but little is known about the underlying microstructural changes; previous work has mainly focused on the corpus callosum. This study is aimed at investigating brain-wide microstructural abnormalities in pediatric PTSD, their relationship to age and sex, and their potential diagnostic value. The microstructure of major white matter tracts was assessed from diffusion tensor images acquired from 24 treatment-naive non-comorbid PTSD patients <18 years and 24 trauma-exposed non-PTSD controls (TENP) matched for age, sex, and years of education. Statistical analyses included pointwise comparisons, correlations with symptom severity, and diagnosis-by-age/sex interactions; support vector machine analyses were conducted to determine whether microstructure distinguishes PTSD from TENP. Compared with TENP, pediatric PTSD patients showed higher fractional anisotropy and lower radial diffusivity in right superior longitudinal fasciculus and lower axial diffusivity in right uncinate fasciculus. These white matter microstructural abnormalities were highly correlated with PTSD symptom severity. No significant diagnosis by age or sex interaction was observed. The pointwise axial diffusivity measurements presented the best PTSD vs. TENP classification performance. In summary, pediatric PTSD patients showed clinically relevant microstructural abnormalities in uncinate and superior longitudinal fasciculus, which extend understanding of pediatric PTSD neurobiology beyond the corpus callosum and have diagnostic potential in distinguishing stressed individuals with and without PTSD.