期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 46, 期 -, 页码 55-59出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2015.02.007
关键词
Major depressive disorder; Inflammation; Kynurenine; Kynurenic acid; Quinolinic acid; Remission; Anhedonia
资金
- National Institute of Mental Health [K01MH096077]
- William K. Warren Foundation
- Oklahoma Tobacco Research Foundation
- Janssen Pharmaceuticals
- Ironwood Pharma, Cambridge, MA
- Johns-Hopkins University
- University of Michigan
- University of Illinois at Chicago
- University of Kansas-Wichita
- Washington University School of Medicine, St. Louis
- Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology
- Janssen Pharmaceuticals, Inc.
- Myriad/Rules Based Medicine, Inc.
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 lcynurenine-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. (C) 2015 Elsevier Inc. All rights reserved.
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