Oxidative Stress and Neuroimaging Alterations in Major Depressive Disorder: A Systematic Review

Major depressive disorder (MDD) is associated with complex neurobiological alterations in which oxidative stress may play a central role; however, direct evidence linking redox biomarkers to alterations in brain chemistry remains limited. This systematic review aimed to synthesize the available evidence on the relationships between oxidative stress and neuroimaging alterations in individuals with MDD. A search was conducted in PubMed, Scopus, and Web of Science (2016-2026) following the PRISMA guidelines, including human studies assessing oxidative biomarkers (central or peripheral) alongside neuroimaging or neurofunctional measures. Four studies met the inclusion criteria (case-control, cross-sectional, and interventional designs). These studies collectively indicate that antioxidant enzymes, glutathione, and malondialdehyde are associated with altered brain activity and connectivity, prefrontal neurochemical changes, and cognitive performance. Overall, the findings support the existence of associations between redox disruption and central nervous system (CNS) alterations in MDD. However, methodological heterogeneity and the limited number of studies highlight the need for further longitudinal and multimodal research to clarify the directionality and clinical relevance of these findings.