Posterior-anterior striatal reorganization after weight restoration in anorexia nervosa is associated with remission outcome: from mice to longitudinal human study

Anorexia nervosa (AN) is a severe psychiatric disorder with high relapse rates despite successful weight restoration. Altered reward processing and an imbalance between goal-directed and habitual control within the striatum have been proposed to contribute to the persistence of maladaptive behaviours, but the striatal mechanisms underlying recovery and relapse remain unclear. Here, we combined cross-species structural MRI with longitudinal clinical characterization to investigate striatal alterations associated with recovery from AN. Mice with deletion of the vesicular acetylcholine transporter (VAChTcKO), a model of maladaptive eating behaviour, showed reduced dorsolateral striatal volume compared with wild-type mice. At baseline, women with AN (n = 71) showed reduced striatal volumes compared with healthy controls (n = 30). Longitudinally, patients with AN (n = 41) and healthy controls (n = 28) were reassessed, revealing substantial recovery of striatal volumes following weight restoration in AN. Posterior-anterior putamen gradient changes differed according to subsequent remission status, with changes in the right putamen gradient predicting relapse. Striatal gradient changes were also associated with goal-directed and habitual behaviour during the slip-of-action task, response consistency during delay discounting, and circulating ghrelin and desacyl ghrelin concentrations. These findings identify longitudinal putamen reorganization as a candidate marker of vulnerability to relapse and link striatal plasticity to reward-related and metabolic processes in AN.