Cortical Alterations in Anorexia Nervosa: A Structural MRI Study

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by persistent restriction of energy intake, intense fear of weight gain, and a distorted perception of body shape and weight. Increasing evidence has demonstrated the presence of structural brain alterations in patients with AN, particularly during the acute underweight phase. However, it remains unclear whether these abnormalities represent a consequence of malnutrition or a pre-existing neurobiological vulnerability. The present cross-sectional case–control study aimed to investigate cortical and subcortical structural alterations in patients with anorexia nervosa using structural magnetic resonance imaging. A total of 112 female participants were included, comprising 63 patients with AN and 49 healthy controls. After matching neuroimaging and clinical data, the final analytical sample consisted of 47 patients and 43 controls. High-resolution T1-weighted MRI scans were processed using FreeSurfer 8.0, applying automated cortical reconstruction and subcortical segmentation pipelines. Analyses included region-of-interest (ROI) approaches, whole-brain vertex-wise analyses, and correlations with clinical variables. Results showed significant reductions in subcortical volumes, particularly involving the thalamus, hippocampus, and brainstem, as well as widespread cortical thinning in frontal, parietal, and cingulate regions in patients with AN compared to healthy controls. Reduced cortical complexity, reflected by alterations in fractal dimension and gyrification index, further supported the presence of disrupted cortical organization. Moreover, heterogeneity analyses highlighted marked inter-individual variability in structural brain alterations, suggesting that neuroanatomical changes in AN may not follow a uniform pattern across patients. These structural alterations were significantly associated with body mass index (BMI), supporting the hypothesis of a direct relationship between the severity of malnutrition and brain structural compromise. Overall, these findings confirm the presence of substantial brain remodelling in anorexia nervosa, likely related to the state of malnutrition, and highlight the potential role of structural neuroimaging as a valuable tool for improving the understanding of the pathophysiology of the disorder and identifying possible prognostic biomarkers.