Dysregulated relationship of inflammation and oxidative stress in major depression

Abstract

Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n = 20) before and after 8 weeks of open-label sertraline treatment (n = 17), compared to healthy non-depressed controls (n = 20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p < 0.05) and were negatively correlated with IL-10 concentrations (p < 0.01). Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/IL-10 (p < 0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio. After MDD subjects were treated with sertraline for 8 weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/IL-10 ratio. These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD. Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment. These findings may help explain the increased risk of comorbid medical illnesses in MDD.

Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels

“…In certain chronic disease states, both of these systems remain activated and may, indeed, form a positive self-sustaining feedback loop or a Bco-activation^state [44]. Over time, such co-activation may lead to a higher risk of depression [5]. Third, Hs-CRP may contribute to the development of depression via an increased white matter hyperintensity burden.…”

“…A large body of evidence suggests that depression is accompanied by activation of inflammatory pathways, reflected by an increased level of inflammatory cytokines [5]. Baune et al [6] found that IL-8 was associated with the first onset of depressive symptoms, whereas plasminogen activator inhibitor-1 (PAI-1) could be regarded as a marker of remitted depression, and Becking et al [7] found that depressed men who developed manic symptoms during Chao-Zhi Tang and Yu-Ling Zhang contributed equally to this work.…”

Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response

“…Studies have described the balance between pro-and antiinflammatory factors to be a more accurate reflection of the inflammatory environment [58,59]. Due to significant interindividual differences in the concentrations of pro-or antiinflammatory factors, here, we evaluated the ratio of pro-to anti-inflammatory factors, which provided a useful measure of the net immunological effect of the circulating cytokines and/ or other factors associated with damage.…”

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

“…Glutathione in particular plays a major role in the redox process (Schafer and Buettner, 2001) and affects the brain by directly detoxifying drugs, ROS, and electrophilic xenobiotics, being a source of cysteine, promoting neurodevelopment and enhancing excitatory glutamatergic neurotransmission (Kohr et al, 1994;Meister, 1988;Shi et al, 2000). Oxidative stress and inflammation contribute notably to major depression (de Morais et al, 2014;Rawdin et al, 2013). In a meta-analysis based on 4908 subjects, depression was associated with high oxidative stress status and with an imbalance towards oxidative markers rather than anti-oxidants (Palta et al, 2014).…”