Anorexia nervosa (AN) is a deadly psychiatric disorder, yet relapse remains common after weight restoration and no objective tools exist to track recovery. AN involves profound disturbances of gastrointestinal interoception, but no clinical tests assess this dysfunction. In this single-blind, randomized-crossover study, 62 weight-restored females with restrictive AN and 57 matched healthy comparisons completed a gastrointestinal detection task using an ingestible vibrating capsule while behavioral, electroencephalographic, and peripheral physiological signals were recorded. AN participants showed reduced perceptual accuracy and higher miss-rates despite intact neural and physiological responses. Computational modeling revealed stronger prior beliefs against perceiving gut sensations, diminished interoceptive precision, and maladaptive learning. Capsule stimulation also induced larger hunger increases in AN. Initial priors, response bias, and stomach unpleasantness predicted six-month relapse, while miss-rate and precision shifts predicted symptom severity. These findings reveal mechanistic disruptions in gastrointestinal interoception that predict relapse, offering scalable biomarkers to personalize treatment and prevent recurrence.
Competing Interest StatementThe authors have declared no competing interest.
Funding StatementThis work was supported by the National Institute of Mental Health (Grant No. R01MH127225 [to SSK]), the William K. Warren Foundation, and the Laureate Institute for Brain Research. SSK was supported, in part, by the Louis Jolyon West Innovation Chair, the UCLA Semel Institute for Neuroscience and Human Behavior, and the UCLA Departments of Psychiatry and Medicine. CV was supported, in part, by the Federation pour la recherche sur le cerveau (FRC), the Union Nationale de Familles et Amis de Personnes Malades et Handicapees Psychiques (UNAFAM), and by the Fondation des Gueules Cassees. The content is solely the responsibility of the authors and the funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Author DeclarationsI 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 was approved by the Western Institutional Review Board. All participants provided written informed consent before participation and were financially compensated for their involvement. ClinicalTrials.gov identifier: #NCT05111977.
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
Data AvailabilityAll data produced in the present study are available upon reasonable request to the authors.
Comments (0)