Systemic oxidatively generated DNA/RNA damage in clinical depression: Associations to symptom severity and response to electroconvulsive therapy

Background: Depression has been associated with increased oxidative stress and hypothesized to accelerate aging. Nucleic acid damage from oxidation is a critical part of the aging process, and a suggested early event in age-related somatic morbidities that are also prevalent in depression, such as dementia and type 2 diabetes. We hypothesized that increased severity of depression is associated with increased systemic oxidatively generated DNA and RNA damage, and that this increase is attenuated by an effective antidepressant treatment. Methods: The urinary excretion of markers of systemic oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N ¼ 28), moderately depressed, non-medicated patients (N ¼ 26) and severely depressed patients eligible for electroconvulsive therapy (ECT) (N¼ 29). In the severely depressed patient group, samples were also obtained 1 week after the completion of ECT. Results: Systemic RNA damage from oxidation, as measured by 8-oxoGuo excretion, was higher with increasing severity of depression (controlsomoderately depressedo severely depressed) (P for trend ¼ 0.004). The 8-oxoGuo excretion was further increased after clinically effective ECT compared with pre-ECT values (P¼0.006). There were no differences in 8-oxodG excretion between the groups or pre- vs. post-ECT. Limitations: Small sample size and the inclusion of both unipolar and bipolar patients in the severely depressed group. Conclusions: Severe depression is associated with increased systemic oxidatively generated RNA damage, which may be an additional factor underlying the somatic morbidity and neurodegenerative features associated with depression. Due to the lack of normalization by clinically effective ECT, the phenomenon does not appear to be causally linked to the depressive state per se.