title: A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase.
abstract: This article highlights the evidence linking depression to increased inflammatory drive and explores putative mechanisms for the association by reviewing both preclinical and clinical literature. The enzyme indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines and may form a link between immune functioning and altered neurotransmission, which results in depression. Increased indoleamine 2,3-dioxygenase activity may cause both tryptophan depletion and increased neurotoxic metabolites of the kynurenine pathway, two alterations which have been hypothesized to cause depression. The tryptophan-kynurenine pathway is comprehensively described with a focus on the evidence linking metabolite alterations to depression. The use of immune-activated groups at high risk of depression have been used to explore these hypotheses; we focus on the studies involving chronic hepatitis C patients receiving interferon-alpha, an immune activating cytokine. Findings from this work have led to novel strategies for the future development of antidepressants including inhibition of indoleamine 2,3-dioxygenase, moderating the cytokines which activate it, or addressing other targets in the kynurenine pathway.
authors.affiliation: Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Christmas
authors.forename: Jp
authors.initials: J
authors.lastname: Potokar
authors.forename: Simon Jc
authors.initials: SJ
authors.lastname: Davies