Oxidative/Nitrosative Stress and Immuno-inflammatory Pathways in Depression: Treatment Implications

George      Anderson; Michael      Maes

doi:10.2174/13816128113196660738

Abstract

This paper reviews recent work on the biological underpinnings of clinical depression emphasizing the crucial role of immunoinflammatory and oxidative and nitrosative stress (O&NS) pathways in driving changes in neuronal regulating tryptophan catabolites (TRYCATs). The essence of the association of O&NS pathways with autoimmune responses in depression is via damage to lipid membranes, anchorage molecules and functional proteins that lead to changes in their chemical structures creating new modified epitopes (neoepitopes), which are highly immunogenic. The abovementioned pathways together with decreased antioxidant levels, including zinc, coenzyme Q10, glutathione and vitamin E, and melatonin are intimately involved in different aspects of depression, including mitochondrial functions and the regulation of cAMP / circadian genes, allowing for impacts across different aspects of symptom patterning. Immuno- inflammatory and O&NS processes may additionally cause alterations in blood-brain barrier permeability and neuroprogression, that is tissue damage, including neurodegeneration and apoptosis, and decreased neurogenesis and neuroplasticity. Activation of those interconnected pathways is relevant to the pathophysiology of acute and chronic depression and the progressive course (staging) of clinical depression. This implies that compounds that target these pathways may be useful to treat acute episodes and prevent further progression of the disease. We herein review some promising compounds, such as melatonin, melatonin receptor agonists, allopregnanolone, PDE4 inhibitors, statins, aspirin, sodium benzoate, tryptophan-enriched diets, and antioxidants, including epigallocatechin gallate, curcumin, quercitin, alpha-lipoic acid and resveratrol.

Keywords: Depression, oxidative, nitrosative, inflammation, kynurenine, circadian, antioxidants, sirtuins, AHr.