Diffusion Tensor Imaging investigation of cerebral white matter in female offspring at high-risk for Eating Disorders

Background: Eating disorders (EDs) are severe psychiatric conditions with significant physical and psychosocial consequences. Emerging evidence suggests that EDs are associated with structural brain abnormalities, yet it remains unclear whether these alterations are consequences of the illness or pre-existing vulnerability markers. This study is the first to examine white matter (WM) integrity in female offspring at familial high risk (FHR) for EDs compared to healthy controls (HC). Methods: Forty-two FHR girls and 46 HC girls underwent diffusion-weighted Magnetic Resonance Imaging (MRI). WM integrity was assessed using fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD), with group comparisons adjusted for pubertal stage and psychiatric diagnoses. Voxel-wise analysis using tract-based spatial statistics (TBSS) was also conducted. Results: Global FA and RD differed significantly in girls at FHR for EDs versus HC in unadjusted analyses, but differences did not persist following covariate adjustment. TBSS revealed a significant cluster of reduced FA in the right inferior fronto-occipital fasciculus (IFOF) in the FHR group (p < .05, Threshold-Free Cluster Enhancement (TFCE)-corrected). Exploratory analyses stratified by maternal diagnosis showed similar FA reductions in girls of mothers with Anorexia Nervosa and Binge Eating Disorder, with overlapping involvement of the IFOF. Conclusions: Our findings suggest that WM-alterations in fronto-parietal associative tracts may represent early neurobiological markers of EDs vulnerability. Further research in larger, longitudinal samples is needed to confirm these preliminary results and clarify their potential as trait markers.