Role of Opioidergic System in Regulating Depression Pathophysiology

There is a clear clinical need for a better understanding of the biological underpinnings of major depressive disorder (MDD), allowing for the development of a treatment that is targeted to pathophysiology. Recent data indicate a role for the endogenous opioidergic system in MDD. This article reviews the roles and physiological interactions of the endogenous opioidergic system in the pathophysiology and heterogeneity of MDD.Articles on the pathophysiology of MDD, as well as on the endogenous opioidergic system and mitochondrial function, form the basis of this review article.The endogenous opioidergic system is intimately linked to wider MDD pathophysiology, including alterations in the gut microbiome, gut permeability, circadian rhythm, amygdala-prefrontal cortex interactions, and mitochondrial function. A decrease in the μ-/κ-opioid receptor ratio is an important mediator of the changes in mood in MDD, with effects not only on neurons, but also on glia and immune cells.The endogenous opioidergic system is intimately interwoven with MDD pathophysiology and provides a relevant target for novel treatment development, as well as providing a focus for the integration of wider MDD pathophysiology.