Regional gray matter alterations in anorexia nervosa: implications for subtype heterogeneity and clinical severity

Evidence indicates a global reduction in gray matter volume (GMV) in anorexia nervosa (AN) due to malnutrition. However, the specific regional GMV alterations that could contribute to the distinct subtypes and clinical presentations of AN remain poorly understood. This study aims to identify regional GMV alterations in AN and its subtypes, and investigate their association with clinical measures in a large sample. The study included 78 adult females with AN (57 restrictive AN-R and 21 binge/purge AN-BP subtype) and 94 healthy females. Voxel-based morphometry was used to compare regional GMV between groups, including AN subtypes. Exploratory correlation of regional GMV with BMI, age of illness onset, illness duration and EDE-Q was performed within the AN group. All analyses were adjusted for total GMV and age. Patients with AN displayed a mixed pattern of higher and lower regional GMV, including limbic, visual and executive regions, with distinct patterns observed in each subtype. Moreover, higher regional GMV was observed in AN-BP compared to AN-R in the right thalamus as well as temporal and occipital regions. Importantly, global volumetric measures did not differ between AN subtypes, indicating that these regional effects primarily reflect localized rather than global changes. In the entire AN group, exploratory analyses revealed that regional GMV correlated negatively with BMI in limbic structures as well as with EDE-Q eating concern subscore in the right insula. Taken together, diverse GMV alterations in acute AN likely reflect neurobiological differences underlying subtype heterogeneity, providing insight into their distinct clinical presentations and potential trait markers.