{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:21:06Z","timestamp":1784550066792,"version":"3.55.0"},"reference-count":127,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Else Kro\u0308ner-Fresenius Foundation for the Residency\/PhD track \u201cTranslational Psychiatry\u201d"},{"name":"International Max Planck Research School for Translational Psychiatry"},{"name":"German Federal Ministry of Education and Research"},{"name":"ESPRIT (Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments","award":["01EE1407E"],"award-info":[{"award-number":["01EE1407E"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Hypothesis<\/jats:title>\n                  <jats:p>Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design<\/jats:title>\n                  <jats:p>Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Results<\/jats:title>\n                  <jats:p>Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/schbul\/sbad065","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T07:37:54Z","timestamp":1683790674000},"page":"1614-1624","source":"Crossref","is-referenced-by-count":29,"title":["Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis"],"prefix":"10.1093","volume":"49","author":[{"given":"Peter","family":"Falkai","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , Germany"},{"name":"Max-Planck-Institute of Psychiatry , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz J","family":"Rossner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian J","family":"Raabe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0244-1024","authenticated-orcid":false,"given":"Daniel","family":"Keeser","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , Germany"},{"name":"NeuroImaging Core Unit Munich (NICUM), University Hospital, Ludwig-Maximilian University , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6208-5180","authenticated-orcid":false,"given":"Isabel","family":"Maurus","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , 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G","family":"Schulze","sequence":"additional","affiliation":[{"name":"Institute for Psychiatric Phenomic and Genomic (IPPG) , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-4023","authenticated-orcid":false,"given":"Andrea","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian University , Munich , Germany"},{"name":"Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of S\u00e3o Paulo (USP) , S\u00e3o Paulo-SP , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"issue":"9","key":"2023112917534329700_CIT0001","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.euroneuro.2011.07.018","article-title":"The size and burden of mental disorders and other disorders of the brain in Europe 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