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The resulting brain-age gap (BAG), defined as predicted brain age minus chronological age, quantifies deviations from age-expected brain characteristics. Structural brain-age acceleration is well established in schizophrenia spectrum disorders (SSD), but the utility of resting-state functional connectivity (rs-FC)\u2013based brain age remains unclear. Here, we trained rs-FC brain-age models on aggregated lifespan data from healthy controls (n\u2009\u2248\u20092200) and evaluated them in four independent SSD case\u2013control cohorts. Across independent cohorts and two brain atlases, SSD showed higher FC-based BAG than healthy controls (\u03b2\u2009\u2248\u20090.4\u20130.6), indicating modest functional brain-age elevation at the group level. However, within SSD, more negative (younger appearing) BAG was associated with poorer cognitive performance, longer duration of illness, and higher neurological soft signs (NSS). Over 12\u201324 weeks, increases in BAG were associated with reductions in NSS motor coordination and hard signs. Together, these findings suggest that rs-FC brain age captures both a small case\u2013control shift and a clinically relevant dimension within SSD that is not well described by uniform \u201cacceleration\u201d. FC-based BAG may therefore reflect heterogeneity in network-level development and reorganization, with younger-appearing functional profiles potentially indexing greater neurodevelopmental burden.<\/jats:p>","DOI":"10.1038\/s41398-026-04426-3","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:05:54Z","timestamp":1788530754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resting-state brain age is associated with cognitive and sensorimotor abnormalities in schizophrenia spectrum disorders: a validation &amp; longitudinal study"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4489-9125","authenticated-orcid":false,"given":"Sebastian","family":"Volkmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Fritze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5172-3303","authenticated-orcid":false,"given":"Dilsa Cemre Akkoc","family":"Altinok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geva","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersoy","family":"Kocak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4518-1749","authenticated-orcid":false,"given":"Julius","family":"Wiegert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Berhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-7569","authenticated-orcid":false,"given":"Heike","family":"Tost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Meyer-Lindenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-9800","authenticated-orcid":false,"given":"Dusan","family":"Hirjak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0261-5063","authenticated-orcid":false,"given":"Emanuel","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"4426_CR1","doi-asserted-by":"publisher","first-page":"106284","DOI":"10.1016\/j.neubiorev.2025.106284","volume":"176","author":"C Fraza","year":"2025","unstructured":"Fraza C, Rutherford S, Bu\u010dkov\u00e1 BR, Beckmann CF, Marquand AF. 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AM-L has received consultant fees from: Agence Nationale de la Recherche, Brain Mind Institute, Brainsway, CISSN (Catania International Summer School of Neuroscience), Daimler und Benz Stiftung, Fondation FondaMental, Hector Stiftung II, Janssen-Cilag GmbH, Lundbeck A\/S, Lundbeckfonden, Lundbeck Int. Neuroscience Foundation, MedinCell, Sage Therapeutics, Techspert.io, The LOOP Z\u00fcrich, University Medical Center Utrecht, von Behring R\u00f6ntgen Stiftung. AM-L has received speaker fees from: Arztekammer Nordrhein, BAG Psychiatrie Oberbayern, Biotest\u00a8 AG, Forum Werkstatt Karlsruhe, International Society of Psychiatric Genetics, Brentwood, Klinik f\u00fcr Psychiatrie und Psychotherapie Ingolstadt, Lundbeck SAS France, med Update GmbH, Merz-Stiftung, Siemens Healthineers, Society of Biological Psychiatry. AM-L has received editorial fees from: American Association for the Advancement of Science, Elsevier, Thieme Verlag. ES received speaker fees from bfd buchholz-fachingormationsdienst GmbH and Lundbeckfonden as well as editorial fees from Lundbeckfonden and the Wellcome Trust. The other authors have declared that there are no conflicts of interest in relation to the subject of this study.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"451"}}