Dysregulation of peripheral oxidative stress and the Nrf2 antioxidant system in Major Depressive Disorder

Background: Oxidative stress and inflammation have been found to be involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the peripheral levels of oxidative stress and the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant system markers in patients with MDD and to evaluate the changes in these markers after 12 weeks of antidepressant treatment. Methods: We consecutively enrolled 104 drug-na & iuml;ve or drug-free patients with an acute episode of MDD and 50 healthy controls (HCs). Plasma levels of Nrf2, phospho-Nrf2 (p-Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), malondialdehyde (MDA), phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2), were measured with the enzyme-linked immunosorbent assay. Results: Patients with MDD exhibited lower levels of the antioxidant system Nrf2, p-Nrf2, HO-1, SOD and higher levels of oxidative stress markers COX-2, PLA2, MDA compared to HCs (all p < 0.001). HO-1 levels differed significantly among melancholic, anxious, and atypical depression (p = 0.002). In addition, we found a negative correlation between somatic symptoms in HAMA scores and Nrf2 levels in MDD group (p = 0.04). At 12 weeks, COX-2 levels significantly increased in the non-remission group compared to baseline (p = 0.039), whereas no significant changes were observed in the remission group. Conclusions: Peripheral oxidative stress and the Nrf2 antioxidant system were found to be dysregulated in patients with MDD. The Nrf2 antioxidant system might be a protective factor for somatic symptoms in MDD, whereas COX-2 might be a risk factor for poor antidepressant efficacy.