The kynurenine pathway in major depression: Haplotype analysis of three related functional candidate genes
Abstract
A consistent finding in major depressive disorder (MDD) research is dysfunction of the immune system. One of the relevant metabolic pathways in this regard is the kynurenine pathway. In patients with major depression, an imbalance between neuroprotective and neurotoxic arms of the pathway with lower plasma kynurenic acid concentration was demonstrated. Therefore, we investigated Single Nucleotide Polymorphism (SNP) and haplotype association of three candidate genes of the three enzymes involved in this metabolism. The three genes, namely, tryptophan hydroxylase 2 (TPH2), kynurenine 3 monooxygenase (KMO) and kynurenine amino transferase 3 (KAT III) SNPs and haplotype association analysis was performed in 338 (266 major depression and 72 bipolar depression) unrelated Caucasian patients with major depressive episodes and 310 age, gender and ethnicity matched controls. In sliding window analyses using PLINK of the haplotypes of KAT III, all windows which include the first SNP (rs12729558), the overall haplotype distribution (OMNIBUS) was significantly different between patients with a major depressive episode and control for all windows, with p-values ranging between 1.75 × 10=5 and 0.006. This is due to the haplotype CGCTCT (referring to 6 SNP window analysis), which is found in about 5.7% of patients and 1.9% of healthy controls. It was due to CGCTCT haplotype and the frequencies of this haplotype in both bipolar patients and patients with major depression showed significantly…
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Plasma kynurenine levels are strongly correlated with depression.
“It may be that changes in mood and fatigue are associated more with the ability of the gut microbi-ota to control host tryptophan metabolism and levels of plasma kynurenine, which are strongly correlated with depression (Claes et al., 2011).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Claes et al., 2011
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- Authors
- Claes, S., Myint, A.-M., Domschke, K., Del-Favero, J., Entrich, K., Engelborghs, S., De Deyn, P., Mueller, N., Baune, B., & Rothermundt, M.
- Affiliations
- KU Leuven (BE)
- Ludwig-Maximilians-Universität München (DE)
- University of Münster (DE)
- University of Antwerp (BE)
- Corresponding author
- Myint, Aye-Mu
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 188
- Issue
- 3
- Pages
- 355-360
- ISSN
- 0165-1781 (ISSN-L)
- OpenAlex
- W2142148369
- Cited by
- 65
- References
- 2
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2022: 7 · 2021: 7 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 8 · 2015: 9 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatry Research (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Advanced Practical Diagnostics n.v., Belgium
- Special Research Fund of the University of Antwerp
- Flemish Government
- Stichting Alzheimer Onderzoek
- Thomas Riellaerts Research Fund
- Institute Born-Bunge
- central Biobank facility
- Neurosearch Antwerp
- Belgian Federal Science Policy Office, Belgium
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- kynurenine pathway, major depressive disorder, bipolar depression, kynurenic acid, tryptophan hydroxylase 2, kynurenine 3-monooxygenase, single nucleotide polymorphisms, haplotype association, immune dysfunction, neuroinflammation, genetic susceptibility
- MeSH terms
- Adult, Transaminases, Major Depressive Disorder, Female, Gene Frequency, Haplotypes, Humans, Kynurenine, Male, Middle Aged, Psychiatric Status Rating Scales, Tryptophan Hydroxylase, Signal Transduction, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Kynurenine 3-Monooxygenase
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