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    Tryptophan Challenge in Healthy Controls and People with Schizophrenia: Acute Effects on Plasma Levels of Kynurenine, Kynurenic Acid and 5-Hydroxyindoleacetic Acid.

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    Author
    Sathyasaikumar, Korrapati V
    Notarangelo, Francesca M
    Kelly, Deanna L
    Rowland, Laura M
    Hare, Stephanie M
    Chen, Shuo
    Mo, Chen
    Buchanan, Robert W
    Schwarcz, Robert
    Date
    2022-08-15
    Journal
    Pharmaceuticals
    Publisher
    MDPI
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/ph15081003
    Abstract
    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.
    Keyword
    cognition
    cytokines
    drug development
    kynurenine pathway
    serotonin
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/19641
    ae974a485f413a2113503eed53cd6c53
    10.3390/ph15081003
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