Structural brain alterations in anorexia nervosa: a global brain volume and anatomical likelihood estimation (ALE) meta-analysis combined with a functional decoding approach

• Global brain volume reductions of 4.79% of gray matter and 2.48% of white matter occur in acute anorexia nervosa (AN), with adolescents showing greater numerical reductions than adults. • Brain volume changes gradually improve during weight rehabilitation, but even 1.5 years after recovery, gray matter volumes of former patients are still significantly reduced compared to healthy controls. • Anatomical likelihood estimation (ALE) analyses indicate widespread reductions of gray matter volume and cortical thickness with key regions in the cingulate gyrus, precentral gyrus, and precuneus. • Spatial colocalization analyses link regions of relative brain volume preservation to brain areas associated with eating, food, threat, and reinforcement (FDR-corrected). Substantial brain volume loss is well-documented during acute anorexia nervosa (AN); however, longitudinal outcomes are unclear. Our comprehensive meta -analysis investigated global and regional structural brain alterations in adult and adolescent individuals with AN by extracting reported brain volume scores and neuroimaging coordinates from the literature. Results showed significant global brain volume reductions in gray matter (GM), white matter (WM), and increases in cerebrospinal fluid (CSF) in acute AN (N = 1130 patients; N = 40 papers), gradually improving upon weight rehabilitation. However, even after 1.5 years of recovery, significantly lower global GM volume compared to healthy controls was found (N = 232 patients; N = 12 papers). Regarding potential regional changes, our search identified 35 eligible papers with neuroimaging coordinates for 412 foci as input for our anatomical likelihood estimation (ALE) analyses. The results revealed widespread reductions of GM volume and cortical thickness, but notably also identified consistently affected brain regions including the cingulate gyrus, precentral gyrus, and precuneus. Spatial colocalization analyses using the Neurosynth data base indicated brain areas associated with eating, food, threat, and reinforcement to be relatively preserved. The findings of our meta -analysis contribute to a better understanding of the underlying pathophysiology of AN, the time course and residuals of brain structural alterations during recovery and clinical implications potentially relevant for more-targeted treatment options.