Premium
Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder
Author(s) -
Munkholm Klaus,
Poulsen Henrik Enghusen,
Kessing Lars Vedel,
Vinberg Maj
Publication year - 2015
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12245
Subject(s) - bipolar disorder , dna damage , medicine , urinary system , pathophysiology , rapid cycling , deoxyguanosine , endocrinology , chemistry , dna , lithium (medication) , oxidative stress , biochemistry
Objectives 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.