{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:53:50Z","timestamp":1774936430594,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371538"],"award-info":[{"award-number":["82371538"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515010705"],"award-info":[{"award-number":["2024A1515010705"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2023A03J0847"],"award-info":[{"award-number":["2023A03J0847"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2023A03J0838"],"award-info":[{"award-number":["2023A03J0838"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2024A03J0219"],"award-info":[{"award-number":["2024A03J0219"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2024A03J0298"],"award-info":[{"award-number":["2024A03J0298"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hippocampal subfield pathology is established in bipolar disorder (BD); yet no studies have investigated these alterations in adolescents at clinical high risk for BD (MDD\u2010Sub), which is a critical gap given adolescence as a neurodevelopmental window for early intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed baseline 3D T1\u2010weighted MRI data from 72 adolescents at Clinical High Risk for BD \u201cMDD\u2010Sub\u201dMDD\u2010Sub vs. MDD\u2010nSub, 74 pure adolescents with MDD (MDD\u2010nSub), and 72 healthy adolescents (HC) aged 12\u201318\u2009years in the sBEAD cohort. Hippocampal subfields were segmented using FreeSurfer 7.3.1. All patients were followed up for at least 12\u2009months to ensure that no participants progressed to schizophrenia or developed new manic symptoms in the MDD\u2010nSub group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MDD\u2010Sub exhibited significant volume reductions in the left cornu ammonis (CA)1, CA3, CA4, molecular layer (ML) and dentate gyrus (DG) even after controlling for medication effects (d<jats:sub>Hc Vs. Mdd\u2010sub<\/jats:sub>\u2009=\u20090.70\u20130.78; d<jats:sub>MDD\u2010Sub vs. MDD\u2010nSub<\/jats:sub>\u2009=\u20090.50\u20130.61). Strikingly, illness duration &gt;\u20091\u2009year predicted volumetric increases in bilateral CA1\/ML\/DG and left CA3\/CA4 (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.13\u20130.21, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), replicated in medication\u2010na\u00efve MDD\u2010Sub (<jats:italic>n<\/jats:italic>\u2009=\u200932). MDD\u2010nSub showed no subfield differences versus HC and MDD\u2010Sub.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This first hippocampal subfield study in BD high\u2010risk adolescents suggests that prodromal\u2010specific left CA1, CA3, CA4, ML, and DG atrophy may help differentiate BD risk from unipolar depression, while nonlinear volumetric trajectories, characterized by early reductions followed by compensatory increases with prolonged illness duration, provide new perspectives on classical neurodegeneration paradigms. These findings provide initial biological support for stage\u2010specific interventions, enhancing neuroplasticity pre\u2010conversion versus neuroprotection post\u2010conversion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.70014","type":"journal-article","created":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T17:52:20Z","timestamp":1741542740000},"page":"232-245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hippocampal Volume Reductions in Key Regions and Their Role in Disease Progression in Adolescents at High Risk for Bipolar Disorder: Findings From the <scp>sBEAD<\/scp> Cohort"],"prefix":"10.1111","volume":"27","author":[{"given":"Xiaofei","family":"Zhang","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University  Guangzhou China"},{"name":"Department of Child and Adolescent Psychiatry Affiliated Brain Hospital, Guangzhou Medical University  Guangzhou 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