title: Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder.
abstract: OBJECTIVE
  The pathophysiological mechanisms underlying bipolar disorder and its multi-system nature are unclear. Oxidatively generated damage to nucleosides has been demonstrated in metabolic disorders; however, the extent to which this occurs in bipolar disorder in vivo is unknown. We investigated oxidatively generated damage to DNA and RNA in patients with bipolar disorder and its relationship with the affective phase compared with healthy control subjects.
  
  
  METHODS
  Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), markers of oxidatively generated DNA and RNA damage, respectively, was measured in 37 rapid cycling patients with bipolar disorder and in 40 age- and gender-matched healthy control subjects. Employing a longitudinal design, repeated measurements of both markers were evaluated in various affective phases in patients with bipolar disorder during a six- to 12-month period and compared with repeated measurements in healthy control subjects.
  
  
  RESULTS
  In linear mixed models, adjusting for demographical, metabolic, and lifestyle factors, the excretion of 8-oxodG and 8-oxoGuo was significantly elevated in euthymic patients with bipolar disorder compared with healthy control subjects, with increases of 40% (p < 0.0005) and 43% (p < 0.0005), respectively. The increased oxidatively generated nucleoside damage was present through all affective phases of the illness, with no significant difference between affective states.
  
  
  CONCLUSIONS
  Our results indicate that bipolar disorder is associated with increased oxidatively generated damage to nucleosides. The findings could suggest a role for oxidatively generated damage to DNA and RNA as a molecular mechanism contributing to the increased risk of medical disorders, shortened life expectancy, and the progressive course of illness observed in bipolar disorder.
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Munkholm
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D001714:Bipolar Disorder / 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; D012313:RNA / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006151:Guanosine; C046215:8-hydroxyguanosine; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine
keywords: 8-oxoGuo; 8-oxodG; bipolar disorder; nucleosides; oxidation; urinary marker