Functional brain connectivity in patients with anorexia nervosa before and after short‐term weight restoration

BACKGROUND: Resting-state functional connectivity (RSFC) studies have consistently identified widespread alterations in the brain's functional network architecture in anorexia nervosa (AN), but it remains unclear whether they are reversible with weight restoration. Furthermore, it is not clear whether there are associations between RSFC and neuroendocrine changes, such as leptin suppression in the underweight state of AN and its increase during short-term weight restoration. METHODS: We first analyzed RSFC data cross-sectionally in young female patients with AN (n = 117) and healthy control participants (n = 117) using network-based statistic (NBS) and graph theory metrics and subsequently explored relationships with plasma leptin as a marker of undernutrition. A subset of patients (n = 73) was reassessed longitudinally after short-term weight restoration [mean body mass index (BMI) increase: 28.0%] to test for changes in identified alterations. RESULTS: NBS revealed increased RSFC in cingulo-occipito-cerebellar circuitry in underweight patients with AN (p = .0018), which decreased over the inpatient weight restoration interval (p < .001). This change correlated negatively with plasma leptin concentrations (p = .042), and plasma leptin appeared to partially mediate the association between BMI increase and RSFC decrease (p = .039), suggesting a possible region-specific modulatory effect. Underweight patients with AN also showed higher characteristic path length (p = .035), indicating reduced integration between brain regions, and higher assortativity (p = .013), indicating stronger coupling among similarly connected regions. Longitudinally, characteristic path length decreased during weight restoration (p = .004), whereas findings for assortativity were suggestive of no change. CONCLUSIONS: The results provide novel longitudinal evidence that functional connectome alterations in AN partially normalize during short-term weight restoration. Speculatively, taking previous results in long-term recovered individuals into consideration, higher assortativity might reflect potential vulnerability for AN. Our finding of a tentative association between the normalization of plasma leptin concentrations and RSFC suggests the possibility that leptin may modulate changes in specific patterns of functional connectivity, offering a potential neurobiological target for novel pharmacotherapies.