{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:17:05Z","timestamp":1788236225162,"version":"build-2803163510"},"posted":{"date-parts":[[2026,8,31]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Innovative Medical Research by the Medical Faculty of M\u00fcnster","award":["LE 1 1 24 09"],"award-info":[{"award-number":["LE 1 1 24 09"]}]},{"name":"German Research Foundation","award":["DA1151\/5-1"],"award-info":[{"award-number":["DA1151\/5-1"]}]},{"name":"German Research Foundation","award":["DA1151\/5-2"],"award-info":[{"award-number":["DA1151\/5-2"]}]},{"name":"German Research Foundation","award":["DA1151\/9-1"],"award-info":[{"award-number":["DA1151\/9-1"]}]},{"name":"German Research Foundation","award":["DA1151\/10-1"],"award-info":[{"award-number":["DA1151\/10-1"]}]},{"name":"German Research Foundation","award":["DA1151\/11-1"],"award-info":[{"award-number":["DA1151\/11-1"]}]},{"name":"German Research Foundation","award":["SFB\/TRR 393, project grant no 521379614"],"award-info":[{"award-number":["SFB\/TRR 393, project grant no 521379614"]}]},{"name":"German Research Foundation","award":["KI 588\/23-1"],"award-info":[{"award-number":["KI 588\/23-1"]}]},{"name":"Interdisciplinary Center for Clinical Research","award":["Dan3\/022\/22"],"award-info":[{"award-number":["Dan3\/022\/22"]}]},{"name":"German Federal Ministry of Education and Research","award":["FKZ-01ER0816"],"award-info":[{"award-number":["FKZ-01ER0816"]}]},{"name":"German Federal Ministry of Education and Research","award":["FKZ-01ER1205"],"award-info":[{"award-number":["FKZ-01ER1205"]}]},{"name":"German Federal Ministry of Education and Research","award":["FKZ-01ER1506"],"award-info":[{"award-number":["FKZ-01ER1506"]}]},{"name":"Germany\u0092s Excellence Strategy","award":["EXC 3066\/1, Project No. 533717223"],"award-info":[{"award-number":["EXC 3066\/1, Project No. 533717223"]}]},{"name":"DYNAMIC center, funded by the LOEWE program of the Hessian Ministry of Science and Arts","award":["LOEWE1\/16\/519\/03\/09.001(0009)\/98"],"award-info":[{"award-number":["LOEWE1\/16\/519\/03\/09.001(0009)\/98"]}]},{"name":"Wellcome Trust funded DIALOG consortium","award":["314138\/Z\/24\/Z"],"award-info":[{"award-number":["314138\/Z\/24\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,31]]},"abstract":"<jats:p>Major depressive disorder (MDD) has been associated with accelerated structural brain aging, yet whether this reflects a pre-existing neurobiological vulnerability, a dynamic acute state effect, or an accumulating biological residual remains unresolved. Across two longitudinal cohorts (N=3220), including a unique sample of 78 initially healthy individuals who transitioned into their first depressive episode during the study course, we systematically tested all three hypotheses. Patients with diagnosed MDD showed elevated MRI-derived brain age relative to healthy controls (1.4 and 2.5 years across cohorts). For the vulnerability hypothesis, individuals scanned prior to their first episode showed no baseline elevation, despite already demonstrating subclinical elevations in self-reported symptom severity, indicating that advanced brain age does not precede illness onset. For the state hypothesis, we found no acceleration of brain aging following the first depressive episode, and longitudinal brain age trajectories were independent of acute clinical symptom severity. Finally, neither episode duration nor recurrence scaled with brain age. Accelerated brain aging in depression is therefore neither an antecedent vulnerability nor an acute state marker of the first episode, but rather a stable biological feature of a long term illness course.<\/jats:p>","DOI":"10.64898\/2026.08.29.26361710","type":"posted-content","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:45:17Z","timestamp":1788234317000},"source":"Crossref","is-referenced-by-count":0,"title":["The timeline of brain aging in major depression: A prospective study from before first-onset to established illness"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2790-9330","authenticated-orcid":false,"given":"Maximilian","family":"Konowski","sequence":"first","affiliation":[{"name":"Institute for Machine Learning in Medicine with focus area psychiatry;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kraus","sequence":"additional","affiliation":[{"name":"Institute for Translational Psychiatry, 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