The role of inflammation and oxidative stress in the pathogenesis of depressive disorders: A review
Abstract
Depressive disorders are among the leading causes of disability worldwide, and a substantial proportion of patients fail to achieve full remission with standard monoaminergic therapies. Consequently, increasing attention has been directed toward alternative pathophysiological mechanisms, particularly chronic inflammation and oxidative stress. A narrative review was conducted based on a comprehensive search of PubMed, Scopus, Web of Science, and PsycINFO databases, including studies published between 2000 and 2025. The literature search strategy relied on precise keywords such as "depressive disorders," "chronic inflammation," "oxidative stress," and various "biological biomarkers." The analysis focused on inflammatory markers, oxidative stress parameters, and their association with depressive disorders. To ensure a rigorous study selection process, a two-stage screening strategy was applied, involving an initial evaluation of titles and abstracts followed by a comprehensive full-text review of the shortlisted articles by the authors. Available evidence indicates that patients with depression frequently exhibit elevated levels of pro-inflammatory markers, including interleukin-6, tumor necrosis factor-alpha, and C-reactive protein. Concurrently, increased production of reactive oxygen species and reduced activity of antioxidant enzymes have been observed. These processes are associated with alterations in neurotransmission, activation of the kynurenine pathway, and impaired neuroplasticity, partly mediated by decreased levels of brain-derived neurotrophic factor. Inflammation and oxidative stress appear to represent important components of the pathophysiology of depression, particularly in a subset of patients. Their potential role as biomarkers and therapeutic targets remains promising but requires further validation in well-designed prospective studies, taking into account the clinical heterogeneity of depressive disorders.