The Role of Mitochondrial Dysfunction-Mediated Changes in Immune Cytokine Expression in the Pathophysiology and Treatment of Major Depressive Disorder.

Recent studies have demonstrated an association between major depressive disorder (MDD) and both mitochondrial dysfunction and alterations in pro-inflammatory cytokine expression, suggesting that such changes may be key drivers of MDD pathogenesis. Mechanistically, changes in mitochondrial function are related to endoplasmic reticulum stress, reactive oxygen species production, oxidative phosphorylation, apoptosis, and disrupted calcium ion homeostasis, all of which trigger the activation of signaling cascades that affect the expression of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferons. Certain factors present in the gut microbiota ecosystem can influence communication between microorganisms and the brain through the neuroendocrine, immune, and autonomic nervous systems, thereby altering mitochondrial function and cytokine production. This review article explores the means through which mitochondria regulate immune cytokine expression and the role of mitochondrial dysfunction in the pathogenesis and treatment of MDD to provide new perspectives for the diagnosis of this disease and the development of novel therapeutic interventions with greater efficacy and improved safety profiles.