Local–global breakdown of cortical similarity networks in anorexia nervosa

Abstract Anorexia nervosa profoundly alters brain structure, yet the large-scale organization of the cortex under severe nutritional stress remains poorly understood. Here we map cortical architecture in 50 patients with anorexia nervosa and 40 healthy controls in this cross-sectional study using Morphometric Inverse Divergence (MIND), a multivariate framework integrating multiple morphometric features into cortical similarity networks. Patients showed a global reduction in morphometric similarity that scaled with nutritional status, with lower body mass index associated with weaker global and network-level connectivity. Disruptions were most prominent in higher-order transmodal networks, with comparatively limited alterations in sensorimotor and visual territories. Region-level effects followed the topology of the structural connectome, and network-based statistics revealed weakened long-range coupling between attentional and limbic–prefrontal circuits. Spatial correspondence with cortical gradients of serotonergic, dopaminergic, μ-opioid and CB1 receptor densities suggests that malnutrition compromises cortical integrity along neurochemically defined axes of vulnerability.