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Here we show that women with AN, at the first medical evaluation, exhibit hyperactivity and hypercortisolemia, together with a reduced immune cell count yet paradoxically showing increased levels of cell activation. One year later, only subjects considered in remission showed greater increases in cortisol and cytokine levels, along with enhanced monocyte differentiation and recruitment. Using the activity-based anorexia (ABA) rat model, we reproduced AN core features, including hypercorticosteronemia, and observed innate-skewed immune profiles, as well as persistent microglial and glucocorticoid receptor (GR) dysfunction in the ventral hippocampus. Pharmacological blockade of GR with RU486 attenuated hyperactivity and reshaped microglial phenotype in the ventral hippocampus. Our results suggest that cortisol elevation and immune cell adaptation may perpetuate disease vulnerability beyond weight normalization, challenging the notion of weight regain as an indicator of remission.<\/jats:p>","DOI":"10.1038\/s41380-026-03756-4","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:41:03Z","timestamp":1784522463000},"page":"6984-6998","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glucocorticoid signalling dysregulation and immune cell adaptation in Anorexia Nervosa"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-1384","authenticated-orcid":false,"given":"Francesca","family":"Mottarlini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-8689","authenticated-orcid":false,"given":"Lorenzo","family":"Da Dalt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Parolaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Baragetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Rizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Taddini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Cigognini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vairano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bertelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Bonacina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-1257","authenticated-orcid":false,"given":"Giuseppe Danilo","family":"Norata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-7706","authenticated-orcid":false,"given":"Fabio","family":"Fumagalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-3146","authenticated-orcid":false,"given":"Lucia","family":"Caffino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"3756_CR1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/eat.22316","volume":"47","author":"FRE Smink","year":"2014","unstructured":"Smink FRE, Van Hoeken D, Oldehinkel AJ, Hoek HW. 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