Neuroimmune, metabolic and oxidative stress pathways in major depressive disorder

This Review examines the role of neuroimmune imbalances and their relationship with metabolism and oxidative stress in the development and progression of major depressive disorder (MDD) and suicidal behaviours. We provide a concise overview of the neuroinflammatory environment and indicators of neuronal injury in the central nervous system of individuals with MDD. Furthermore, we explore the evidence for perturbations in both the peripheral and central immune system, T cell activation versus T regulatory cell depletion, intracellular signalling networks including nuclear factor-κB, lipid metabolism and neuroprotection. Last, we examine the mechanisms by which psychological stressors, translocation of Gram-negative bacteria, viral infections such as SARS-CoV-2 and metabolic syndrome can contribute to neuroimmune imbalances and, consequently, the acute phase of MDD.