Mitochondrial Dysfunction in Depression

Abstract

Background: Depression is the most debilitating neuropsychiatric disorder with significant impact on socio-occupational and well being of individual. The exact pathophysiology of depression is still enigmatic though various theories have been put forwarded. There are evidences showing that mitochondrial dysfunction in various brain regions is associated with depression. Recent findings have sparked renewed appreciation for the role of mitochondria in many intracellular processes coupled to synaptic plasticity and cellular resilience. New insights in depression pathophysiology are revolving around the impairment of neuroplasticity. Mitochondria have potential role in ATP production, intracellular Ca2+ signalling to establish membrane stability, reactive oxygen species (ROS) balance and to execute the complex processes of neurotransmission and plasticity. So understanding the various concepts of mitochondrial dysfunction in pathogenesis of depression indubitably helps to generate novel and more targeted therapeutic approaches for depression treatment.

Objective: The review was aimed to give a comprehensive insight on role of mitochondrial dysfunction in depression.

Result: Targeting mitochondrial dysfunction and enhancing the mitochondrial functions might act as potential target for the treatment of depression.

Conclusion: Literature cited in this review highly supports the role of mitochondrial dysfunction in depression. As impairment in the mitochondrial functions lead to the generation of various insults that exaggerate the pathogenesis of depression. So, it is useful to study mitochondrial dysfunction in relation to mood disorders, synaptic plasticity, neurogenesis and enhancing the functions of mitochondria might show promiscuous effects in the treatment of depressed patients.

Fig. (1)

Exposure to different stressful situations leads to increase ROS production, increased levels proinflammatory cytokines, increased nitrosative stress and decrease in antioxidant enzymes level which ultimately leads to reduce OXPHOS, activation of apoptotic pathway and causes mtDNA damage as consequence of which there is decreased mitochondrial biogenesis, increased ROS production, apoptosis of neuronal cells, impaired translation of mitochondrial ETC complex proteins and decreased ATP production which results into mitochondrial dysfunction. Neurogenesis, synaptic plasticity and neuronal transmission, the important parameters for successful adaptation to the stressful conditions are also compromised due to mitochondrial dysfunction hence also play an important role in major depression.