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We tested a novel transdiagnostic hypothesis that atypical connectivity of the default mode network (DMN) mediates the association between childhood trauma (CT) and cognitive impairment. The sample of 1851 individuals aged 18-25 included 433 patients with depression, eating disorders, alcohol use disorder, psychosis and ADHD) and were recruited as part of the ESTRA\/STRATIFY\/IMAGEN studies. CT was measured using the Childhood Trauma Questionnaire (CTQ). The CANTAB spatial working memory task was administered to assess cognition. Four a priori seeds of the default mode network (DMN) were measured during face processing, namely the medial prefrontal cortex (PFC), right lateral parietal (LP), left lateral parietal (LP) and posterior cingulate cortex (PCC), according to the Harvard-Oxford Cortical and Subcortical Atlas (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.cma.mgh.harvard.edu\/fsl_atlas.html\" ext-link-type=\"uri\">http:\/\/www.cma.mgh.harvard.edu\/fsl_atlas.html<\/jats:ext-link>\n                    ) as implemented in CONN. Patients had significantly reduced DMN connectivity between the four chosen DMN seeds and the rest of the brain. Reduced DMN connectivity mediated the association between higher CT and worse cognitive performance. Our findings are transdiagnostic in nature with stronger effects in some regions observed in depression, and suggest one transdiagnostic cortical network via which CT\u2019s effects on cognition are transmitted.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09400-1","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:05:18Z","timestamp":1772021118000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterising a stress-sensitive default mode network (DMN) deficit in major psychiatric disorders"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1718-7302","authenticated-orcid":false,"given":"Sinead","family":"King","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-3434","authenticated-orcid":false,"given":"Zuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-7281","authenticated-orcid":false,"given":"Robert","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7796-8234","authenticated-orcid":false,"given":"Frauke","family":"Nees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Bobou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4595-1144","authenticated-orcid":false,"given":"Tobias","family":"Banaschewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7421","authenticated-orcid":false,"given":"Gareth J.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-4914","authenticated-orcid":false,"given":"Arun L. 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He received conference support or speaker\u2019s fee by Janssen, Medice and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker\u2019s fees from Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. M. John Broulidakis receives a salary from medical device manufacturer Emteq Labs for which he works as a research scientist. Emteq Labs had no role, financial or otherwise, in the STRATIFY or IMAGEN projects or this paper in particular. Views expressed in this paper do not necessarily reflect those of Emteq Labs. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or potential competing interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"603"}}