Structural neuroimaging signatures of anorexia nervosa features in a mixed sample enriched for disease vulnerability

ABSTRACT Brain-behavior relationships that could provide insight into risk-associated pathophysiology have not been thoroughly assessed in anorexia nervosa (AN). Therefore, we sought to identify grey and white matter signatures of AN symptoms and risk factors (trait anxiety, set-shifting impairment) in a sample enriched for AN vulnerability, including acute and remitted AN patients and their unaffected sisters ( n = 72, aged 18 – 48 years). MRI/DTI data were acquired on a 3T scanner and processed with Freesurfer and FSL TBSS. Relationships between clinical variables of interest and regional subcortical volume, vertex-wise cortical surface architecture (thickness, surface area, local gyrification), and voxel-wise white matter microstructure (FA, MD) were tested with separate linear regressions, including age, BMI, lifetime AN diagnosis, and intracranial volume as covariates, where appropriate. Significance was determined using a Bonferroni-corrected threshold, p ( t ) ≤ 0.001. We detected distinct associations linking AN symptoms to lateral occipital cortical thickness and insular/cingulate gyrification and trait anxiety to lingual cortical thickness and superior parietal gyrification, and we detected overlapping associations linking AN symptoms and set-shifting impairment to frontoparietal gyrification. No other brain-behavior relationships emerged. Our findings suggest that variations in site-specific cortical morphology could give rise to core features of AN and shared temperamental and cognitive-behavioral risk factors for AN.