{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T12:56:33Z","timestamp":1768308993725,"version":"3.49.0"},"reference-count":19,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Schizophrenia spectrum disorders (SSD) are debilitating psychiatric illnesses\n                        that require extensive pharmacologic, cognitive, and functional management.\n                        SSD patients are often prescribed different medications, most commonly\n                        antipsychotics, which bear numerous side effects. Recently, accumulating\n                        evidence has shown epigenetic aging changes in SSD. However, the effects of\n                        antipsychotic medications on this phenomenon remain unexplored.<\/jats:p>\n                  <jats:p>We investigated whether antipsychotic medications are associated with\n                        epigenetic age acceleration (EAA) in 153 SSD patients. EAA was estimated\n                        using six different epigenetic clocks, based on the methylation patterns of\n                        peripheral blood cells.<\/jats:p>\n                  <jats:p>The analysis revealed some evidence of aging deceleration based on the Hannum\n                        DNAm Age in individuals on antipsychotic polypharmacy, relative to their\n                        monopharmacy counterparts (mean difference=\u20130.59 years, p=0.0109), which was\n                        only nearing significance after adjusting for multiple comparisons\n                            (padjusted=0.0654). In sex-specific analysis, only females\n                        displayed significantly decelerated epigenetic aging in the polypharmacy\n                        group in three of the six clocks. Furthermore, we observed no dose-dependent\n                        effects of antipsychotics on EAA in all clocks using three dose\n                        standardization methods (daily defined dose, chlorpromazine equivalents, and\n                        percent of maximum allowed dose).<\/jats:p>\n                  <jats:p>The findings suggest that antipsychotic treatment may modulate biological\n                        aging in SSD; however, this effect is not dose-dependent. Moreover, there\n                        appears to be an interplay between sex, polypharmacy, and epigenetic aging.\n                        These findings contribute to our understanding of the biological effects of\n                        antipsychotic treatment, and future research in this area is key for\n                        weighing the benefits and the risks of pharmacological management of\n                        SSD.<\/jats:p>","DOI":"10.1055\/a-2668-0722","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T23:44:07Z","timestamp":1762213447000},"page":"35-43","source":"Crossref","is-referenced-by-count":0,"title":["Antipsychotic Polypharmacy and Epigenetic Age Acceleration in\n                    Schizophrenia"],"prefix":"10.1055","volume":"59","author":[{"given":"George","family":"Nader","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Yung","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matisse","family":"Ducharme","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Gerretsen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Graff","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Toronto, CAMH, Toronto,\n                    Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-clinpsy-032813-153657","article-title":"Excess early mortality in schizophrenia","volume":"10","author":"T M Laursen","year":"2014","journal-title":"Annu Rev Clin Psychol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.3390\/healthcare10122366","article-title":"Mortality in schizophrenia-spectrum disorders: Recent advances in understanding\n                    and management","volume":"10","author":"V Peritogiannis","year":"2022","journal-title":"Healthcare"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.biopsych.2023.10.023","article-title":"Accelerated pace of aging in schizophrenia: Five case-control studies","volume":"95","author":"A Caspi","year":"2024","journal-title":"Biol Psychiatry"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.schres.2021.04.005","article-title":"Accelerated aging in the brain, epigenetic aging in blood, and polygenic risk\n                    for schizophrenia","volume":"231","author":"J 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versus monotherapy","volume":"14","author":"M D Fisher","year":"2014","journal-title":"BMC Psychiatry"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"109805","DOI":"10.1016\/j.pnpbp.2019.109805","article-title":"Accelerated extrinsic epigenetic aging and increased natural killer cells in\n                    blood of suicide completers","volume":"98","author":"S Okazaki","year":"2020","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"ref14","first-page":"22","article-title":"The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development\n                    and validation of a structured diagnostic psychiatric interview for DSM-IV and\n                    ICD-10","volume":"59","author":"D V Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00406-023-01622-w","article-title":"GWAS of biological aging to find longevity genes in schizophrenia","volume":"274","author":"J Qian","year":"2024","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: A flexible and comprehensive bioconductor package for the analysis of\n                    infinium DNA methylation microarrays","volume":"30","author":"M J Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"ref19","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Foundation for Statistical\n                        Computing","year":"2024"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13148-024-01660-8","article-title":"Meta-analysis of epigenetic aging in schizophrenia reveals multifaceted\n                    relationships with age, sex, illness duration, and polygenic risk","volume":"16","author":"AP S Ori","year":"2024","journal-title":"Clin Epigenetics"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"113646","DOI":"10.1016\/j.psychres.2020.113646","article-title":"Biological aging in schizophrenia and psychosis severity: DNA methylation\n                    analysis","volume":"296","author":"O Dada","year":"2021","journal-title":"Psychiatry Res"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41537-022-00277-1","article-title":"Antipsychotics function as epigenetic age regulators in human neuroblastoma\n                    cells","volume":"8","author":"J Du","year":"2022","journal-title":"Schizophrenia"}],"container-title":["Pharmacopsychiatry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2668-0722.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T23:33:16Z","timestamp":1768260796000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2668-0722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":19,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2026,1,12]]},"published-print":{"date-parts":[[2026,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2668-0722","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0176-3679","1439-0795"],"issn-type":[{"value":"0176-3679","type":"print"},{"value":"1439-0795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}