Early-onset restrictive eating disorders (rEO-ED) encompass a heterogeneous group of conditions, including early-onset anorexia nervosa (EO-AN) and avoidant restrictive food intake disorders (ARFID). Almost nothing is known about the consequences of rEO-ED on brain development. We performed the largest comparison of MRI-derived brain features in children and early adolescents (<13 years) with EO-AN (n=124), ARFID (n=50), and typically developing individuals (TD, n=112). Despite similar body mass index (BMI) distributions, EO-AN and ARFID showed divergent structural patterns, suggesting independent brain mechanisms. Half the regional brain measures were correlated with BMI in EO-AN and none in ARFID, indicating a partial mediation of EO-AN signal by BMI. EO-AN was associated with a widespread pattern of thinner cortex, while underweight ARFID patients exhibited smaller surface area and subcortical volumes than TD. Future studies will be required to partition the contribution of low BMI vs. ED mechanisms in neurodevelopmental disorders.

The authors have declared no competing interest.

The authors would like to thank all participants and their families who participated in the study, as well as the Clinical Investigation Center, Robert Debre Hospital, Paris, France, for managing the study. This study was supported by funding from the Fondation de France (2015-00059547) and the Institut Pasteur (Universite de Paris, CNRS UMR 3571, Contrat interface hospitalier). CAM, PMT, SE, and RD acknowledge funding from the National Institute of Mental Health (U01MH136221). This work was supported by the German Research Foundation (SFB 940 TP C03, EH 367/5-1, EH 367/7-1).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study followed the principles of the Declaration of Helsinki and the Good Clinical Practice (ICH GCP) standards. Data from patients with eating disorders were studied following the French regulation (MR-004) and approved by the local Ethics Committee (CEER - 'Comite d'Evaluation de l'Ethique des Projets de Recherche' of the Robert Debre hospital: 2022-610ter). Data from the control group were used under authorizations of the PARIS (ref: Inserm C07-33 - CEER of Robert Debre hospital 2008-A00019-46) and DEVine cohorts (ref: CCP 3772-RM, Protocol 'Commissariat aux Energies Atomique et Alternative' number: 100 054). All participants and their guardians provided written informed consent.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All derived imaging data produced in the present study are available upon reasonable request to the authors