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

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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.

TidsskriftTranslational Psychiatry
Antal sider8
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Financial support was granted from various foundations: The Research Fund of the Mental Health Services—Capital Region of Denmark, the Innovation Fund Denmark (GrantID: 4108-00004B), the Independent Research Fund Denmark (GrantID: DFF-6120-00038), the Lundbeck Foundation alliance BrainDrugs (GrantID: R279-2018-1145), the Research Council of Rigshospitalet, the Augustinus Foundation (GrantID: 16-0058), the G.J. Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, and Eva and Robert Voss Hansen Foundation. GESUS was funded by the Region Zealand Foundation, Naestved Hospital Foundation, Naestved commune, Johan and Lise Boserup Foundation, TrygFonden, Johannes Fog’s Foundation, Region Zealand, Naestved Hospital, The National Board of Health, and the Local Government Denmark Foundation.

Publisher Copyright:
© 2022, The Author(s).

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