Tryptophan Challenge in Healthy Controls and People with Schizophrenia: Acute Effects on Plasma Levels of Kynurenine, Kynurenic Acid and 5-Hydroxyindoleacetic Acid.
Author
Sathyasaikumar, Korrapati VNotarangelo, Francesca M
Kelly, Deanna L
Rowland, Laura M
Hare, Stephanie M
Chen, Shuo
Mo, Chen
Buchanan, Robert W
Schwarcz, Robert
Date
2022-08-15Journal
PharmaceuticalsPublisher
MDPIType
Article
Metadata
Show full item recordAbstract
he pivotal tryptophan (TRP) metabolite kynurenine is converted to several neuroactive compounds, including kynurenic acid (KYNA), which is elevated in the brain and cerebrospinal fluid of people with schizophrenia (SZ) and may contribute to cognitive abnormalities in patients. A small proportion of TRP is metabolized to serotonin and further to 5-hydroxyindoleacetic acid (5-HIAA). Notably, KP metabolism is readily affected by immune stimulation. Here, we assessed the acute effects of an oral TRP challenge (6 g) on peripheral concentrations of kynurenine, KYNA and 5-HIAA, as well as the cytokines interferon-γ, TNF-α and interleukin-6, in 22 participants with SZ and 16 healthy controls (HCs) using a double-blind, placebo-controlled, crossover design. TRP raised the levels of kynurenine, KYNA and 5-HIAA in a time-dependent manner, causing >20-fold, >130-fold and 1.5-fold increases in kynurenine, KYNA and 5-HIAA concentrations, respectively, after 240 min. According to multivariate analyses, neither baseline levels nor the stimulating effects of TRP differed between participants with SZ and HC. Basal cytokine levels did not vary between groups, and remained unaffected by TRP. Although unlikely to be useful diagnostically, measurements of circulating metabolites following an acute TRP challenge may be informative for assessing the in vivo efficacy of drugs that modulate the neosynthesis of KYNA and other products of TRP degradation.Data Availibility
Data is contained within the article.Identifier to cite or link to this item
http://hdl.handle.net/10713/19641ae974a485f413a2113503eed53cd6c53
10.3390/ph15081003
Scopus Count
Collections
Related articles
- Role of d-amino acid oxidase in the production of kynurenine pathway metabolites from d-tryptophan in mice.
- Authors: Notarangelo FM, Wang XD, Horning KJ, Schwarcz R
- Issue date: 2016 Feb
- Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia.
- Authors: Chiappelli J, Notarangelo FM, Pocivavsek A, Thomas MAR, Rowland LM, Schwarcz R, Hong LE
- Issue date: 2018 Jul
- Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia.
- Authors: Kindler J, Lim CK, Weickert CS, Boerrigter D, Galletly C, Liu D, Jacobs KR, Balzan R, Bruggemann J, O'Donnell M, Lenroot R, Guillemin GJ, Weickert TW
- Issue date: 2020 Nov
- Peripheral and cerebral metabolic abnormalities of the tryptophan-kynurenine pathway in a murine model of major depression.
- Authors: Laugeray A, Launay JM, Callebert J, Surget A, Belzung C, Barone PR
- Issue date: 2010 Jun 26
- Altered serum levels of kynurenine metabolites in patients affected by cluster headache.
- Authors: Curto M, Lionetto L, Negro A, Capi M, Perugino F, Fazio F, Giamberardino MA, Simmaco M, Nicoletti F, Martelletti P
- Issue date: 2015