Molecular correlates of mitochondrial dysfunctions in major depression: Evidence from clinical and rodent studies

Major depressive disorder (MDD) is one of the most prevalent stress-related mental disorders worldwide. Several biological mechanisms underlying the pathophysiology of MDD have been proposed, including endocrine disturbances, neurotransmitter deficits, impaired neuronal plasticity, and more recently, mitochondrial dysfunctions. In this review, we provide an overview of relevant molecular correlates of mitochondrial dysfunction in MDD, based on findings from clinical studies and stress-induced rodent models. We also compare differences and similarities between the phenotypes of MDD patients and animal models. Our analysis of the literature reveals that both MDD and stress are associated, in humans and animals, with changes in mitochondrial biogenesis, redox imbalance, increased oxidative damages of cellular macromolecules, and apoptosis. Yet, a considerable amount of conflicting data exist and therefore, the translation of findings from clinical and preclinical research to novel therapies for MDD remains complex. Further studies are needed to advance our understanding of the molecular networks and biological mechanisms involving mitochondria in the pathophysiology of MDD.