Oxidation induced DNA damage and base excision repair during a current episode and after remission in bipolar and unipolar depression

Abstract

Introduction: Emerging evidence suggest a central role of DNA damage/repair mechanisms in pathogenesis of mood disorders. We aimed to understand DNA damage/repair during a current depres-sive episode and after remission in bipolar and unipolar disorders Method: Twenty- four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were com-pleted at baseline and at remission after 8 weeks. Measure of DNA damage was urine 8- OHdG levels as assessed by liquid chromatog-raphy tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG- 1 were determined from cDNA extracted from blood samples, using real time- polymerase chain reaction. Results: At baseline, patients presented significantly higher levels of 8- OHdG (P = .008), and lower gene expression of OGG- 1 (P = .024) compared to controls. Levels of neither 8- OHdG nor OGG- 1 expres-sions differed between BD and UD. In patients who remitted by the 8th week (n = 30), 8- OHdG decreased significantly (P = .001), and gene expression levels of OGG- 1 increased by 2.95 times compared to baseline levels (P = .001). All comparisons were adjusted for age, sex, smoking status and body mass index. Conclusion: Our results suggest that both bipolar and unipolar de-pression present reversible increases in oxidative DNA damage, and reversible impairments in base excision repair. The causal relation-ship between DNA damage and repair requires further exploration.