title: Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder.
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.
authors: Laureate Institute for Brain Research, Tulsa, OK, USA; Faculty of Community Medicine, University of Tulsa, Tulsa, OK, USA. Electronic address: jsavitz@laureateinstitute.org.
authors: Jonathan
authors: J
authors: Savitz
authors: Janssen Pharmaceuticals of Johnson & Johnson, Inc., Titusville, NJ, USA.
authors: Wayne C
authors: WC
authors: Drevets
authors: Laureate Institute for Brain Research, Tulsa, OK, USA; Department of Psychiatry, University of Oklahoma College of Medicine, Tulsa, OK, USA.
authors: Brent E
authors: BE
authors: Wurfel
authors: Laureate Institute for Brain Research, Tulsa, OK, USA.
authors: Bart N
authors: BN
authors: Ford
authors: Laureate Institute for Brain Research, Tulsa, OK, USA; Faculty of Community Medicine, University of Tulsa, Tulsa, OK, USA.
authors: Patrick S F
authors: PS
authors: Bellgowan
authors: Laureate Institute for Brain Research, Tulsa, OK, USA.
authors: Teresa A
authors: TA
authors: Victor
authors: Laureate Institute for Brain Research, Tulsa, OK, USA; College of Engineering, University of Oklahoma, Tulsa, OK, USA.
authors: Jerzy
authors: J
authors: Bodurka
authors: Department of Surgery, University of Oklahoma College of Medicine, Tulsa, OK, USA; Department of Psychiatry, University of Oklahoma College of Medicine, Tulsa, OK, USA; Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, OK, USA; Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA.
authors: T Kent
authors: TK
authors: Teague
authors: Division of Internal Medicine, Department of Symptom Research, MD Anderson Cancer Center, Houston, TX, USA.
authors: Robert
authors: R
authors: Dantzer
mesh_terms: D000293:Adolescent; D000328:Adult; D002853:Chromatography, Liquid; D003865:Major Depressive Disorder / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007736:Kynurenic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017378:Quinolinic Acid / Q000097:blood*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D017378:Quinolinic Acid; D007736:Kynurenic Acid
keywords: Anhedonia; Inflammation; Kynurenic acid; Kynurenine; Major depressive disorder; Quinolinic acid; Remission