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Damage generated by oxidation of nucleosides may be implicated in BD pathophysiology; however, evidence from <jats:italic>in vivo<\/jats:italic> studies is limited and the extent of state-related alterations is unclear. This prospective study investigated for we believe the first time the damage generated by oxidation of DNA and RNA strictly in patients with type I BD in a manic or mixed state and subsequent episodes and remission compared with healthy control subjects. Urinary excretion of 8-oxo-deoxyguanosine (8-oxodG) and 8-oxo-guanosine (8-oxoGuo), valid markers of whole-body DNA and RNA damage by oxidation, respectively, was measured in 54 patients with BD I and in 35 healthy control subjects using a modified ultraperformance liquid chromatography and mass spectrometry assay. Repeated measurements were evaluated in various affective phases during a 6- to 12-month period and compared with repeated measurements in healthy control subjects. Independent of lifestyle and demographic variables, a 34% (<jats:italic>P&lt;<\/jats:italic>0.0001) increase in RNA damage by oxidation across all affective states, including euthymia, was found in patients with BD I compared with healthy control subjects. Increases in DNA and RNA oxidation of 18% (<jats:italic>P&lt;<\/jats:italic>0.0001) and 8% (<jats:italic>P<\/jats:italic>=0.02), respectively, were found in manic\/hypomanic states compared with euthymia, and levels of 8-oxodG decreased 15% (<jats:italic>P&lt;<\/jats:italic>0.0001) from a manic or mixed episode to remission. The results indicate a role for DNA and RNA damage by oxidation in BD pathophysiology and a potential for urinary 8-oxodG and 8-oxoGuo to function as biological markers of diagnosis, state and treatment response in BD.<\/jats:p>","DOI":"10.1038\/tp.2016.141","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T13:43:52Z","timestamp":1470750232000},"page":"e867-e867","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Increased DNA and RNA damage by oxidation in patients with bipolar I disorder"],"prefix":"10.1038","volume":"6","author":[{"given":"A S","family":"Jacoby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Vinberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H E","family":"Poulsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L V","family":"Kessing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-0359","authenticated-orcid":false,"given":"K","family":"Munkholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,8,9]]},"reference":[{"key":"BFtp2016141_CR1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.4088\/JCP.v68n0612","volume":"68","author":"TM Laursen","year":"2007","unstructured":"Laursen TM, Munk-Olsen T, Nordentoft M, Mortensen PB . 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