Posterior-anterior striatal reorganization after weight restoration in anorexia nervosa is associated with remission outcome: from mice to longitudinal human study
- 1Universite Paris Cite, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Vulnerability to Psychiatric and Addictive Disorders, 75014 Paris
Abstract
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, including cross-sectional analyses in mice and longitudinal neuroimaging and clinical assessments in patients with AN, to investigate striatal alterations associated with recovery. Male mice with deletion of the vesicular acetylcholine transporter (VAChTcKO; n = 9), a model of maladaptive eating behaviour, showed reduced dorsolateral striatal volume compared with wild-type mice (n=9). 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, goal-directed and habitual control, reward processing, and metabolic processes in AN.
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BibTeX
@misc{zarrabi2026posterioranterior,
title = {{Posterior-anterior striatal reorganization after weight restoration in anorexia nervosa is associated with remission outcome: from mice to longitudinal human study}},
author = {A. Adl Zarrabi and A. Cachia and V. Tolle and C. Da Costa and N. Lebrun and C. Debacker and S. Charron and M. Chakravarty and S. Daumas and S. El Mestikawy and C. Oppenheim and P. Gorwood and P. Duriez},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.23.26366116},
url = {https://www.medrxiv.org/content/10.64898/2026.10.23.26366116v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Posterior-anterior striatal reorganization after weight restoration in anorexia nervosa is associated with remission outcome: from mice to longitudinal human study
AU - A. Adl Zarrabi
AU - A. Cachia
AU - V. Tolle
AU - C. Da Costa
AU - N. Lebrun
AU - C. Debacker
AU - S. Charron
AU - M. Chakravarty
AU - S. Daumas
AU - S. El Mestikawy
AU - C. Oppenheim
AU - P. Gorwood
AU - P. Duriez
PY - 2026
DA - 2026/10/23
PB - medRxiv
DO - 10.64898/2026.10.23.26366116
UR - https://www.medrxiv.org/content/10.64898/2026.10.23.26366116v1
AB - 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, including cross-sectional analyses in mice and longitudinal neuroimaging and clinical assessments in patients with AN, to investigate striatal alterations associated with recovery. Male mice with deletion of the vesicular acetylcholine transporter (VAChTcKO; n = 9), a model of maladaptive eating behaviour, showed reduced dorsolateral striatal volume compared with wild-type mice (n=9). 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, goal-directed and habitual control, reward processing, and metabolic processes in AN.
ER -