Oxidative stress, inflammation and treatment response in major depression

Objective: Increased inflammation and oxidative stress have been shown in Major Depressive Disorder(MDD), although there is significant heterogeneity across studies. Whether markers of inflammation andoxidative stress are associated with antidepressant treatment response in MDD is currently unclear. Thegoals of the present study are to investigate markers of inflammation and oxidative stress in unmedicatedMDD subjects and controls and test the relationship between these markers and antidepressant responsein MDD subjects.Methods: Interleukin (IL)-6, tumor necrosis factor (TNF)-, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in bloodsamples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severitywas rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somaticallyhealthy and free from medications that could interfere with inflammation and oxidative stress mark-ers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI)antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated.Antidepressant treatment “response” was defined as ≥50% decrease in HDRS ratings over 8 weeks oftreatment.Results: After controlling for the effects of age, sex, body mass index and smoking, MDD subjects hadsignificantly higher levels of IL-6 (p < 0.001), TNF- (p < 0.001), 8-OHdG (p = 0.018), and F2-isoprostanes(p = 0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levelsof F2-isoprostanes at baseline (p = 0.006), and after eight weeks of treatment (p = 0.031). Non-respondersshowed a significant increase in 8-OHdG over the course of treatment (p = 0.021), whereas Respondersshowed a significant decrease in IL-6 over the course of treatment (p = 0.019).Conclusion: Our results are in line with previous reports of increased levels of markers of inflammationand oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higherbaseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressantresponse was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.