{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:16:53Z","timestamp":1793089013741,"version":"4.5.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n Importance<\/jats:title>\n Anorexia nervosa (AN) is a deadly psychiatric disorder with relapse rates approaching 50% after weight restoration. Disrupted gastrointestinal interoception may underlie persistent symptoms and relapse vulnerability.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine behavioral, computational, neural, and physiological markers of gastrointestinal interoception in weight-restored individuals with AN and test their association with relapse.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This crossover trial was a single-blind, within-participant, randomized (block-order) trial conducted at the Laureate Institute for Brain Research between August 2021 and February 2025. Participants were females with weight-restored restrictive AN and age- and sex-matched healthy comparators (HCs). All participants ingested a vibrating capsule that delivered counterbalanced blocks of normal- and enhanced-intensity gut stimulation. Behavioral detection performance, electroencephalography, peripheral physiology, and computational modeling were used to assess interoception.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Experimental-session measures included interoceptive accuracy, prior beliefs, interoceptive precision, learning rates, gastric-evoked potentials (GEPs), and hunger. Main clinical outcomes at 6 months included relapse status and symptom severity.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The cohort included 62 female participants with weight-restored restrictive AN (mean [SD] age, 18.9 [4.5] years) and 57 age- and sex-matched healthy comparators (HCs; mean [SD] age, 20.7 [5.3] years). Six-month follow-up data were collected for 54 participants with AN. Compared with HCs, participants with AN showed lower perceptual accuracy (Cohen\n d<\/jats:italic>\n \u2009=\u2009\u22120.98; 95% CI, \u22121.51 to \u20130.44;\n P<\/jats:italic>\n \u2009=\u2009.001) and higher miss rates (Cohen\n d<\/jats:italic>\n \u2009=\u20091.02; 95% CI, 0.55 to 1.48;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Computational modeling revealed in the AN group stronger prior expectations that capsule vibrations would not be present (Cohen\n d<\/jats:italic>\n \u2009=\u2009\u22120.31; 95% CI, \u22120.67 to 0.05;\n P<\/jats:italic>\n \u2009=\u2009.05), greater shifts in interoceptive precision between blocks (Cohen\n d<\/jats:italic>\n \u2009=\u20090.38; 95% CI, 0.02 to 0.75;\n P<\/jats:italic>\n \u2009=\u2009.01), and learning asymmetries (vibration: Cohen\n d<\/jats:italic>\n \u2009=\u2009\u22120.40; 95% CI, \u22120.77 to \u22120.04;\n P<\/jats:italic>\n \u2009=\u2009.007; no-vibration: Cohen\n d<\/jats:italic>\n \u2009=\u20090.35; 95% CI, \u22120.02 to 0.71;\n P<\/jats:italic>\n \u2009=\u2009.01). GEP amplitudes did not differ by group but were correlated with accuracy and learning in AN. Capsule stimulation induced greater hunger increases in AN (interaction: \u03b7\n 2<\/jats:sup>\n p\u2009=\u20090.04,\n P<\/jats:italic>\n \u2009=\u2009.04; AN: Cohen\n d<\/jats:italic>\n \u2009=\u20090.94; 95% CI, 0.57 to 1.30; HCs: Cohen\n d<\/jats:italic>\n \u2009=\u20090.40; 95% CI, 0.03 to 0.77). At follow-up, relapse was predicted by initial priors (odds ratio [OR], 3.82; 95% CI, 1.02 to 15.91;\n P<\/jats:italic>\n \u2009=\u2009.05), response bias (OR, 5.37; 95% CI, 1.15 to 32.04;\n P<\/jats:italic>\n \u2009=\u2009.04), and stomach unpleasantness (OR, 5.73; 95% CI, 1.38 to 33.5;\n P<\/jats:italic>\n \u2009=\u2009.03), while eating disorder symptom severity was predicted by miss rate (\u03b2\u2009=\u20091.05;\n \n R\n 2<\/jats:sup>\n <\/jats:italic>\n \u2009=\u20090.08;\n P<\/jats:italic>\n \u2009=\u2009.05), difference in interoceptive precision (\u03b2\u2009=\u20095.84;\n \n R\n 2<\/jats:sup>\n <\/jats:italic>\n \u2009=\u20090.16;\n P<\/jats:italic>\n \u2009=\u2009.004), and initial priors (\u03b2\u2009=\u2009\u22122.99;\n \n R\n 2<\/jats:sup>\n <\/jats:italic>\n \u2009=\u20090.09;\n P<\/jats:italic>\n \u2009=\u2009.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study of weight-restored females with AN, gastrointestinal interoception was disrupted across multiple domains, including reduced accuracy detecting gut signals, maladaptive priors, rigid learning, and abnormal hunger rating. Several interoceptive markers predicted relapse and symptom severity at follow-up. These findings support the use of ingestible mechanosensory probes and computational modeling as scalable tools to monitor treatment response and guide relapse prevention in eating disorders.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05111977<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2026.1301","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:30:37Z","timestamp":1781710237000},"page":"902","source":"Crossref","is-referenced-by-count":2,"title":["Gastrointestinal Interoception and Relapse in Anorexia Nervosa"],"prefix":"10.1001","volume":"83","author":[{"given":"Charles","family":"Verdonk","sequence":"first","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"},{"name":"UMR VIFASOM, Universit\u00e9 de Paris, Paris, France"},{"name":"French Armed Forces Biomedical Research Institute, Br\u00e9tigny-sur-Orge, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keller","family":"Mink","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Choquette","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Moseman","sequence":"additional","affiliation":[{"name":"Laureate Eating Disorders Program, Tulsa, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Mayeli","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"},{"name":"Oxley College of Health Sciences, University of Tulsa, Tulsa, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Paulus","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"},{"name":"Oxley College of Health Sciences, University of Tulsa, Tulsa, Oklahoma"},{"name":"Deputy Editor, JAMA Psychiatry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Smith","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"},{"name":"Oxley College of Health Sciences, University of Tulsa, Tulsa, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahib S.","family":"Khalsa","sequence":"additional","affiliation":[{"name":"Laureate Institute for Brain Research, Tulsa, Oklahoma"},{"name":"Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"7","key":"yoi260028r1","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1001\/archgenpsychiatry.2011.74","article-title":"Mortality rates in patients with anorexia nervosa and other eating disorders. a meta-analysis of 36 studies.","volume":"68","author":"Arcelus","year":"2011","journal-title":"Arch Gen Psychiatry"},{"issue":"12","key":"yoi260028r2","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/S2215-0366(15)00356-9","article-title":"Anorexia nervosa: aetiology, assessment, and treatment.","volume":"2","author":"Zipfel","year":"2015","journal-title":"Lancet Psychiatry"},{"issue":"6","key":"yoi260028r3","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/YCO.0000000000000453","article-title":"Relapse in anorexia nervosa: a systematic review and meta-analysis.","volume":"31","author":"Berends","year":"2018","journal-title":"Curr Opin Psychiatry"},{"key":"yoi260028r4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40337-017-0145-3","article-title":"What happens after treatment? a systematic review of relapse, remission, and recovery in anorexia nervosa.","volume":"5","author":"Khalsa","year":"2017","journal-title":"J Eat Disord"},{"issue":"6","key":"yoi260028r5","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.bpsc.2017.12.004","article-title":"Interoception and mental health: a roadmap.","volume":"3","author":"Khalsa","year":"2018","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"6","key":"yoi260028r6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0033-3182(70)71578-8","article-title":"Gastric perceptivity in normal, obese and schizophrenic subjects.","volume":"11","author":"Coddington","year":"1970","journal-title":"Psychosomatics"},{"issue":"2","key":"yoi260028r7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/1098-108X(198321)2:2<15::AID-EAT2260020203>3.0.CO;2-6","article-title":"Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia.","volume":"2","author":"Garner","year":"1983","journal-title":"Int J Eat Disord"},{"issue":"8","key":"yoi260028r8","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrn2682","article-title":"New insights into symptoms and neurocircuit function of anorexia nervosa.","volume":"10","author":"Kaye","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"yoi260028r9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/7854_2024_470","article-title":"Perceptual dysfunction in eating disorders.","volume":"74","author":"Reilly","year":"2025","journal-title":"Curr Top Behav Neurosci"},{"key":"yoi260028r10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/7854_2010_85","article-title":"Neurocircuity of eating disorders.","volume":"6","author":"Kaye","year":"2011","journal-title":"Curr Top Behav Neurosci"},{"key":"yoi260028r11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3389\/fpsyt.2020.00281","article-title":"The role of interoception in the pathogenesis and treatment of anorexia nervosa: a narrative review.","volume":"11","author":"Jacquemot","year":"2020","journal-title":"Front Psychiatry"},{"issue":"7","key":"yoi260028r12","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/eat.22387","article-title":"Altered interoceptive awareness in anorexia nervosa: effects of meal anticipation, consumption and bodily arousal.","volume":"48","author":"Khalsa","year":"2015","journal-title":"Int J Eat Disord"},{"issue":"1","key":"yoi260028r14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11920-022-01318-3","article-title":"Gastrointestinal interoception in eating disorders: charting a new path.","volume":"24","author":"Khalsa","year":"2022","journal-title":"Curr Psychiatry Rep"},{"issue":"1","key":"yoi260028r15","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1038\/s41467-023-39058-4","article-title":"Parieto-occipital ERP indicators of gut mechanosensation in humans.","volume":"14","author":"Mayeli","year":"2023","journal-title":"Nat Commun"},{"key":"yoi260028r16","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopsycho.2021.108152","article-title":"Gut inference: a computational modelling approach.","volume":"164","author":"Smith","year":"2021","journal-title":"Biol Psychol"},{"key":"yoi260028r17","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev-clinpsy-050718-095617","article-title":"An active inference approach to interoceptive psychopathology.","volume":"15","author":"Paulus","year":"2019","journal-title":"Annu Rev Clin Psychol"},{"issue":"4","key":"yoi260028r18","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijchp.2023.100383","article-title":"Mental health meets computational neuroscience: a predictive Bayesian account of the relationship between interoception and multisensory bodily illusions in anorexia nervosa.","volume":"23","author":"Lernia","year":"2023","journal-title":"Int J Clin Health Psychol"},{"issue":"1","key":"yoi260028r19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.tins.2020.09.012","article-title":"Computational models of interoception and body regulation.","volume":"44","author":"Petzschner","year":"2021","journal-title":"Trends Neurosci"},{"issue":"1","key":"yoi260028r20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1017\/S0033291717001635","article-title":"Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa.","volume":"48","author":"Berner","year":"2018","journal-title":"Psychol Med"},{"issue":"10","key":"yoi260028r21","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.12925","article-title":"Estimation of eating disorders prevalence by age and associations with mortality in a simulated nationally representative US cohort.","volume":"2","author":"Ward","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"9","key":"yoi260028r22","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/eat.23580","article-title":"Examining the significance of age of onset in persons with lifetime anorexia nervosa: comparing child, adolescent, and emerging adult onsets in nationally representative U.S. study.","volume":"54","author":"Grilo","year":"2021","journal-title":"Int J Eat Disord"},{"issue":"1","key":"yoi260028r23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jpsychores.2013.10.009","article-title":"Adolescent anorexia nervosa: cognitive performance after weight recovery.","volume":"76","author":"Lozano-Serra","year":"2014","journal-title":"J Psychosom Res"},{"issue":"3","key":"yoi260028r24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/eat.22462","article-title":"Gastrointestinal complications associated with anorexia nervosa: a systematic review.","volume":"49","author":"Norris","year":"2016","journal-title":"Int J Eat Disord"},{"issue":"8","key":"yoi260028r25","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1002\/eat.20274","article-title":"Does the frequency of anxiety and depressive disorders differ between diagnostic subtypes of anorexia nervosa and bulimia?","volume":"39","author":"Godart","year":"2006","journal-title":"Int J Eat Disord"},{"key":"yoi260028r26","first-page":"22","article-title":"The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.","volume":"59","author":"Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"issue":"6","key":"yoi260028r27","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1037\/h0031246","article-title":"Nonparametric indexes for sensitivity and bias: computing formulas.","volume":"75","author":"Grier","year":"1971","journal-title":"Psychol Bull"},{"issue":"1","key":"yoi260028r28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3758\/BF03207704","article-title":"Calculation of signal detection theory measures.","volume":"31","author":"Stanislaw","year":"1999","journal-title":"Behav Res Methods Instrum Comput"},{"issue":"1","key":"yoi260028r29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jneumeth.2003.10.009","article-title":"EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis.","volume":"134","author":"Delorme","year":"2004","journal-title":"J Neurosci Methods"},{"key":"yoi260028r30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.neuroimage.2016.01.042","article-title":"Automatic EEG-assisted retrospective motion correction for fMRI (aE-REMCOR).","volume":"129","author":"Wong","year":"2016","journal-title":"Neuroimage"},{"key":"yoi260028r31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jneumeth.2016.09.012","article-title":"Real-time EEG artifact correction during fMRI using ICA.","volume":"274","author":"Mayeli","year":"2016","journal-title":"J Neurosci Methods"},{"issue":"4","key":"yoi260028r32","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0049-16.2016","article-title":"Computational phenotyping in psychiatry: a worked example.","volume":"3","author":"Schwartenbeck","year":"2016","journal-title":"eNeuro"},{"key":"yoi260028r33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmp.2021.102632","article-title":"A step-by-step tutorial on active inference and its application to empirical data.","volume":"107","author":"Smith","year":"2022","journal-title":"J Math Psychol"},{"issue":"4","key":"yoi260028r34","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/eat.23255","article-title":"On bells, saliva, and abdominal pain or discomfort: early aversive visceral conditioning and vulnerability for anorexia nervosa.","volume":"53","author":"Zucker","year":"2020","journal-title":"Int J Eat Disord"},{"issue":"2","key":"yoi260028r35","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3758\/s13415-020-00777-6","article-title":"Keep your interoceptive streams under control: an active inference perspective on anorexia nervosa.","volume":"20","author":"Barca","year":"2020","journal-title":"Cogn Affect Behav Neurosci"},{"key":"yoi260028r36","doi-asserted-by":"crossref","DOI":"10.1016\/j.cpr.2020.101905","article-title":"Cognitive flexibility in acute anorexia nervosa and after recovery: a systematic review.","volume":"81","author":"Miles","year":"2020","journal-title":"Clin Psychol Rev"},{"key":"yoi260028r37","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.neubiorev.2017.08.011","article-title":"Anorexia nervosa and bulimia nervosa: a meta-analysis of executive functioning.","volume":"83","author":"Hirst","year":"2017","journal-title":"Neurosci Biobehav Rev"},{"issue":"1","key":"yoi260028r39","doi-asserted-by":"crossref","first-page":"92","DOI":"10.5334\/cpsy.109","article-title":"Updating prospective self-efficacy beliefs about cardiac interoception in anorexia nervosa: an experimental and computational study.","volume":"8","author":"Saramandi","year":"2024","journal-title":"Comput Psychiatr"},{"issue":"8","key":"yoi260028r40","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1001\/jamapsychiatry.2025.0812","article-title":"Anorexia nervosa: facts, frustrations, and the future.","volume":"82","author":"Phillipou","year":"2025","journal-title":"JAMA Psychiatry"},{"issue":"6","key":"yoi260028r41","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1002\/eat.23555","article-title":"Brain-gut psychotherapies: promising tools to address gastrointestinal problems in patients with eating disorders.","volume":"54","author":"Wildes","year":"2021","journal-title":"Int J Eat Disord"},{"issue":"5","key":"yoi260028r42","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1162\/jocn_a_02131","article-title":"Neural mechanisms determining the duration of task-free, self-paced visual perception.","volume":"36","author":"Baror","year":"2024","journal-title":"J Cogn Neurosci"},{"issue":"3","key":"yoi260028r43","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/hbm.20567","article-title":"Cortical sources of visual evoked potentials during consciousness of executive processes.","volume":"30","author":"Babiloni","year":"2009","journal-title":"Hum Brain Mapp"},{"key":"yoi260028r44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/2050-2974-1-21","article-title":"Alexithymia and eating disorders: a critical review of the literature.","volume":"1","author":"Nowakowski","year":"2013","journal-title":"J Eat Disord"},{"key":"yoi260028r13","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/978-3-031-68521-7_9","volume-title":"Interoception: A Comprehensive Guide","author":"Khalsa","year":"2024"},{"key":"yoi260028r38","doi-asserted-by":"crossref","unstructured":"Saramandi? A, Crucianelli? L, Koukoutsakis? A, . Belief updating about interoception and body size estimation in anorexia nervosa.? PsyArXiv. Posted April 28, 2022. doi:10.31234\/osf.io\/rntsf","DOI":"10.31234\/osf.io\/rntsf"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2850389\/jamapsychiatry_verdonk_2026_oi_260028_1788289936.90539.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:00:40Z","timestamp":1788361240000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2850389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2026.1301","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}