Systemic DNA and RNA damage from oxidation after serotonergic treatment of unipolar depression

Abstract

Previous studies have indicated that antidepressants that inhibit the serotonin transporter reduces oxidative stress. DNA and RNA damage from oxidation is involved in aging and a range of age-related pathophysiological processes. Here, we studied the urinary excretion of markers of DNA and RNA damage from oxidation, 8-oxodG and 8-oxoGuo, respectively, in the NeuroPharm cohort of 100 drug-free patients with unipolar depression and in 856 non-psychiatric community controls. Patients were subsequently treated for 8 weeks with escitalopram in flexible doses of 5–20 mg; seven of these switched to duloxetine by week 4, as allowed by the protocol. At week 8, 82 patients were followed up clinically and with measurements of 8-oxodG/8-oxoGuo. Contextual data were collected in patients, including markers of cortisol excretion and low-grade inflammation. The intervention was associated with a substantial reduction in both 8-oxodG/8-oxoGuo excretion (25% and 10%, respectively). The change was not significantly correlated to measures of clinical improvement. Both markers were strongly and negatively correlated to cortisol, as measured by the area under the curve for the full-day salivary cortisol excretion. Surprisingly, patients had similar levels of 8-oxodG excretion and lower levels of 8-oxoGuo excretion at baseline compared to the controls. We conclude that intervention with serotonin reuptake inhibitors in unipolar depression is associated with a reduction in systemic DNA and RNA damage from oxidation. To our knowledge, this to date the largest intervention study to characterize this phenomenon, and the first to include a marker of RNA oxidation.

Specific prediction of mortality by oxidative stress‐induced damage to RNA vs. DNA in humans

“…The markers do not show diurnal variation (Grew et al, 2014 ) and are highly stable for 10+ years when stored at −20 degrees Celsius (Henriksen et al, 2021 ). We recently demonstrated that the storage time did not influence the marker levels in the present cohorts (Jorgensen et al, 2022 ). The exact subcellular origins of the molecules have not been completely clarified, but the cellular release of 8‐oxodG is thought to stem from enzymatic repair of DNA and/or the nucleotide pool, whereas the release of 8‐oxoGuo is thought to stem from the degradation of RNA.…”

Oxidative DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder

“…Increasing data suggest that there is a signi cant elevation in 8-OH-dG levels in depression [4,28]. However, follow-up studies suggest that the increase in acute depression is reversible and returns to normal values after the resolution of depressive symptoms [20,21,29]. It should be noted that the siblings with previous episodes were euthymic at the time of inclusion in our study.…”

Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

“…In a meta-analysis, DNA oxidation damage seem to be higher in MDD patients compared to controls [ 109 ]. Interestingly, modifications of urinary 8-oxo-7,8-dihydroguanosine (8-oxoGuo), a biomarker of RNA oxidation, were also observed in MDD [ 115 , 116 ]. Increased hippocampal RNA oxidation was also observed in a postmortem study of depressed patients [ 117 ].…”