Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder

Jonathan Savitz, Wayne C. Drevets, Brent E. Wurfel, Bart N. Ford, Patrick S.F. Bellgowan, Teresa A. Victor, Jerzy Bodurka, T. Kent Teague, Robert Dantzer

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Low-grade inflammation is characteristic of a subgroup of currently depressed patients with major depressive disorder (dMDD). It may lead to the activation of the kynurenine-metabolic pathway and the increased synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). Nevertheless, few studies have examined whether abnormalities in this pathway are present in remitted patients with MDD (rMDD). Here we compared the serum concentrations of kynurenine metabolites, measured using high performance liquid chromatography with tandem mass spectrometry, across 49 unmedicated subjects meeting DSM-IV-TR criteria for MDD, 21 unmedicated subjects meeting DSM-IV-TR criteria for rMDD, and 58 healthy controls (HCs). There was no significant group difference in the concentrations of the individual kynurenine metabolites, however both the dMDD group and the rMDD group showed a reduction in KynA/QA, compared with the HCs. Further, there was an inverse correlation between KynA/QA and anhedonia in the dMDD group, while in the rMDD group, there was a negative correlation between lifetime number of depressive episodes and KynA/QA as well as a positive correlation between the number of months in remission and KynA/QA. Our results raise the possibility that a persistent abnormality exists within the kynurenine metabolic pathway in MDD that conceivably may worsen with additional depressive episodes. The question of whether persistent abnormalities in kynurenine metabolism predispose to depression and/or relapse in remitted individuals remains unresolved.

Original languageEnglish
Pages (from-to)55-59
Number of pages5
JournalBrain, Behavior, and Immunity
Volume46
DOIs
StatePublished - 1 May 2015
Externally publishedYes

Keywords

  • Anhedonia
  • Inflammation
  • Kynurenic acid
  • Kynurenine
  • Major depressive disorder
  • Quinolinic acid
  • Remission

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