Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals with Anorexia Nervosa - A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in grey matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy controls. Recent weight regain before scanning may explain some of this heterogeneity across studies. To clarify the extent, magnitude, and dependencies of grey matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. We analyzed T1-weighted structural MRI scans assessed with standardized methods from 685 female AN patients and 963 female healthy controls across 22 sites worldwide. In addition to a case-control comparison, we conducted a three-group analysis comparing healthy controls to acutely underweight AN patients (n = 466), and to those in treatment and partially weight-restored (n = 251). In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area, were sizable (Cohen9s d up to 0.95), widespread and co-localized with hub regions. Highlighting the effects of undernutrition, these deficits associated with lower BMI in the AN sample and were less pronounced in partially weight-restored patients. Notably, the effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.