Oxidative stress, inflammation and treatment response in major depression

Abstract

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 and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. Methods Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. 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 of treatment. Results After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p<0.001), TNF-α (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 levels of F2-isoprostanes at baseline (p=0.006), and after eight weeks of treatment (p=0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p=0.021), whereas Responders showed 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 inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.

Severity of anxiety– but not depression– is associated with oxidative stress in Major Depressive Disorder

“…However, our finding is in line with a previous report from our group that GSH levels were not decreased in MDD subjects compared to healthy controls, despite the fact that F2-isoprostanes were elevated (Lindqvist et al, 2017). Our findings may indicate that chronic oxidative stress results in a compensatory but inadequate increase in GSH synthesis in attempt to reduce further oxidative damage (Andreazza et al, 2009), but this is purely hypothetical.…”

“…Oxidative stress data from subsets of this sample have been previously reported in relation to hypotheses not explored in the present study (Lindvist et al, 2017; Rawdin et al, 2013). MDD diagnoses were determined using the Structured Clinical Interview for the DSM-IV (First et al, 1997).…”

“…Peripheral markers of increased oxidative stress, as well as decreased antioxidants, have been reported in individuals with MDD (Black et al, 2015, Lindqvist et al, 2017 and Palta et al, 2014) and in individuals with anxiety disorders, including panic disorder, social phobia, and obsessive compulsive disorder (Atmaca et al, 2008, Kuloglu et al, 2002 and Ozdemir et al, 2009). To our knowledge, only two prior studies examined the relationship between oxidative stress and specific symptom dimensions of MDD.…”

“…Indeed, many studies have found evidence of increased oxidative stress in MDD, as well as increased gene expression regulated by oxidative stress, suggesting that this is an important contributor to depression pathophysiology (Lindqvist et al, 2017, Maes et al, 2011, Mellon et al, 2016 and Wolkowitz et al, 2011). …”

Tauroursodeoxycholic acid produces antidepressant‐like effects in a chronic unpredictable stress model of depression via attenuation of neuroinflammation, oxido‐nitrosative stress, and endoplasmic reticulum stress

“…In previous studies, the oxidative and nitrosative stresses have been widely reported to be involved in the pathogenesis of depression . Here, we studied the influence of TUDCA on NO, MDA, and GSH.…”