Title:Role of Proinflammatory Cytokines in Dopaminergic System Disturbances, Implications for Anhedonic Features of MDD
Volume: 23
Issue: 14
Author(s): Zihang Pan, Joshua D. Rosenblat, Walter Swardfager and Roger S. McIntyre*
Affiliation:
- Professor of Psychiatry and Pharmacology, University of Toronto, Head, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street - Toronto, ON,Canada
Keywords:
Anhedonia, Major Depressive Disorder (MDD), inflammation, tetrahydrobiopterin, kynurenine pathway, cytokines, oxidative
stress, treatment implications.
Abstract: Anhedonia, characterized by a loss of interest and/or pleasure in previously enjoyable activities, is an
important diagnostic criterion of Major Depressive Disorder (MDD). Converging evidence implicates a causal
relationship between proinflammatory cytokines and behavioural disturbances that characterize anhedonia in the
context of MDD. Additionally, anhedonia has been implicated in disturbances of key central dopaminergic modulatory
pathways. Emerging research into the roles of tetrahydrobiopterin, a cytokine-targeted co-enzyme in the
synthesis of dopamine, and kynurenine, a product of inflammation-sensitive breakdown of tryptophan via indoleamine
2, 3-dioxygenase, have shed new light into the role of inflammation in mediating anhedonic behaviours.
The following narrative review is not meant to be comprehensive, but highlights the roles of both tetrahydrobiopterin
and kynurenine pathways in anhedonia, and discusses a potential mechanism of action via oxidative
stress and excitotoxicity. Treatment implications are discussed, with an emphasis on anti-inflammatories as
complements to current treatments of anhedonia and MDD.
