title: Role of Proinflammatory Cytokines in Dopaminergic System Disturbances, Implications for Anhedonic Features of MDD.
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.
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street - Toronto, ON, Canada.
authors.forename: Zihang
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Hurvitz Brain Science Program, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rosenblat
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
authors.affiliation: Professor of Psychiatry and Pharmacology, University of Toronto, Head, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street - Toronto, ON, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004298:Dopamine
keywords: Anhedonia; Major Depressive Disorder (MDD); cytokines; inflammation; kynurenine pathway; oxidative
  stress; tetrahydrobiopterin; treatment implications.