{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:24:12Z","timestamp":1790454252968,"version":"4.1.0"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"\n Importance<\/jats:title>\n All-cause mortality and the risk for age-related medical disease is increased in individuals with psychiatric illness, but the underlying biological mechanisms are not known. Oxidative stress on nucleic acids (DNA and RNA; NA-OXS) is a molecular driver of aging and a potential pathophysiological mechanism in a range of age-related disorders.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To study the levels of markers of NA-OXS in a large cohort of community-dwelling individuals with and without psychiatric illness and to evaluate their association with prospective all-cause mortality.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cohort study used a combined cohort of participants from 2 population-based health studies: the Danish General Suburban Population Study (January 2010 to October 2013) and nondiabetic control participants from the Vejle Diabetes Biobank study (March 2007 to May 2010). Individual history of psychiatric illness was characterized using register data on psychiatric diagnoses and use of psychotropic drugs before baseline examination. Urinary markers of systemic RNA (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and DNA (8-oxo-7,8-dihydro-2\u2019-deoxyguanosine [8-oxodG]) damage from oxidation were measured by ultraperformance liquid chromatography\u2013tandem mass spectrometry. Cox proportional hazard regression models were applied for survival analyses, using register-based all-cause mortality updated to May 2023. The follow-up time was up to 16.0 years.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n History of psychiatric illness.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Mortality risk according to psychiatric illness status and 8-oxoGuo or 8-oxodG excretion level.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 7728 individuals were included (3983 [51.5%] female; mean [SD] age, 58.6 [11.9] years), 3095 of whom (40.0%) had a history of psychiatric illness. Mean (SD) baseline 8-oxoGuo was statistically significantly higher in individuals with psychiatric illness than in those without (2.4 [1.2] nmol\/mmol vs 2.2 [0.9] nmol\/mmol;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), whereas 8-oxodG was not. All-cause mortality was higher in the psychiatric illness group vs the no psychiatric illness group (hazard ratio [HR], 1.44; 95% CI, 1.27-1.64;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and increased sequentially with each increasing tertile of 8-oxoGuo excretion in both groups to an almost doubled risk in the psychiatric illness\/high 8-oxoGuo group compared to the no psychiatric illness\/low 8-oxoGuo reference group (HR, 1.99; 95% CI, 1.58-2.52;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). These results persisted after adjustment for a range of potential confounders and in a sensitivity analysis stratified for sex.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This study establishes systemic oxidative stress-induced damage to RNA as a potential mechanism in the accelerated aging observed in psychiatric disorders and urinary 8-oxoGuo as a potentially useful marker of mortality risk in individuals with psychiatric illness.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2024.0052","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T11:00:56Z","timestamp":1709722856000},"page":"516","source":"Crossref","is-referenced-by-count":15,"title":["Oxidative Stress-Induced Damage to RNA and DNA and Mortality in Individuals with Psychiatric Illness"],"prefix":"10.1001","volume":"81","author":[{"given":"Anders","family":"Jorgensen","sequence":"first","affiliation":[{"name":"Psychiatric Center Copenhagen, Mental Health Services, Frederiksberg Hospital, Copenhagen, Denmark"},{"name":"Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Brandslund","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark"},{"name":"Faculty of Health Science, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Ellervik","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Laboratory Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Clinical Biochemistry, Zealand University Hospital, K\u00f8ge, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University Hospital Copenhagen, Bispebjerg and Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Weimann","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University Hospital Copenhagen, Bispebjerg and Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel Porsborg","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital, Hiller\u00f8d, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Torp-Pedersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital, Hiller\u00f8d, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Kragh","family":"Andersen","sequence":"additional","affiliation":[{"name":"Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Balslev","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Psychiatric Center Copenhagen, Mental Health Services, Frederiksberg Hospital, Copenhagen, Denmark"},{"name":"Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Enghusen","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital, Hiller\u00f8d, Denmark"},{"name":"Department of Endocrinology, Copenhagen University Hospital Bispebjerg-Frederiksberg, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"6","key":"ybr240001r1","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s42255-022-00591-z","article-title":"Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo.","volume":"4","author":"Murphy","year":"2022","journal-title":"Nat Metab"},{"issue":"9","key":"ybr240001r2","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1001\/jamapsychiatry.2022.2066","article-title":"Association of oxidative stress-induced nucleic acid damage with psychiatric disorders in adults: a systematic review and meta-analysis.","volume":"79","author":"Jorgensen","year":"2022","journal-title":"JAMA Psychiatry"},{"issue":"10211","key":"ybr240001r3","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1016\/S0140-6736(19)32316-5","article-title":"A comprehensive analysis of mortality-related health metrics associated with mental disorders: a 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