title: Increased DNA and RNA damage by oxidation in patients with bipolar I disorder.
abstract: The mechanisms underlying bipolar disorder (BD) and the associated medical burden are unclear. Damage generated by oxidation of nucleosides may be implicated in BD pathophysiology; however, evidence from in vivo 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% (P<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% (P<0.0001) and 8% (P=0.02), respectively, were found in manic/hypomanic states compared with euthymia, and levels of 8-oxodG decreased 15% (P<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.
authors: Psychiatric Center Copenhagen, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: A S
authors: AS
authors: Jacoby
authors: Psychiatric Center Copenhagen, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: M
authors: M
authors: Vinberg
authors: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet and Department of Clinical Pharmacology, Bispebjerg Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: H E
authors: HE
authors: Poulsen
authors: Psychiatric Center Copenhagen, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: L V
authors: LV
authors: Kessing
authors: Psychiatric Center Copenhagen, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: K
authors: 0000-0001-6437-0359
authors: K
authors: Munkholm
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D018692:Antimanic Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D016022:Case-Control Studies; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011446:Prospective Studies; D012313:RNA / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D006151:Guanosine; C046215:8-hydroxyguanosine; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine