Title:Mitochondria: A Connecting Link in the Major Depressive Disorder Jigsaw
Volume: 17
Issue: 6
Author(s): Shilpa Sharma and Ravi S. Akundi*
Affiliation:
- Neuroinflammation Research Lab, Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi,India
Keywords:
Major depressive disorder, mitochondria, ATP, purinergic receptors, neuroinflammation, PBAIDs.
Abstract:
Background: Depression is a widespread phenomenon with varying degrees of pathology
in different patients. Various hypotheses have been proposed for the cause and continuance of
depression. Some of these include, but not limited to, the monoamine hypothesis, the neuroendocrine
hypothesis, and the more recent epigenetic and inflammatory hypotheses.
Objective: In this article, we review all the above hypotheses with a focus on the role of mitochondria
as the connecting link. Oxidative stress, respiratory activity, mitochondrial dynamics and metabolism
are some of the mitochondria-dependent factors which are affected during depression. We
also propose exogenous ATP as a contributing factor to depression.
Result: Literature review shows that pro-inflammatory markers are elevated in depressive individuals.
The cause for elevated levels of cytokines in depression is not completely understood. We propose
exogenous ATP activates purinergic receptors which in turn increase the levels of various proinflammatory
factors in the pathophysiology of depression.
Conclusion: Mitochondria are integral to the function of neurons and undergo dysfunction in major
depressive disorder patients. This dysfunction is reflected in all the various hypotheses that have
been proposed for depression. Among the newer targets identified, which also involve mitochondria,
includes the role of exogenous ATP. The diversity of purinergic receptors, and their differential
expression among various individuals in the population, due to genetic and environmental (prenatal)
influences, may influence the susceptibility and severity of depression. Identifying specific
receptors involved and using patient-specific purinergic receptor antagonist may be an appropriate
therapeutic course in the future.
