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dc.contributor.authorSathyasaikumar, Korrapati V
dc.contributor.authorNotarangelo, Francesca M
dc.contributor.authorKelly, Deanna L
dc.contributor.authorRowland, Laura M
dc.contributor.authorHare, Stephanie M
dc.contributor.authorChen, Shuo
dc.contributor.authorMo, Chen
dc.contributor.authorBuchanan, Robert W
dc.contributor.authorSchwarcz, Robert
dc.date.accessioned2022-08-30T13:41:38Z
dc.date.available2022-08-30T13:41:38Z
dc.date.issued2022-08-15
dc.identifier.urihttp://hdl.handle.net/10713/19641
dc.description.abstracthe 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.en_US
dc.description.urihttps://doi.org/10.3390/ph15081003en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.relationData is contained within the article.en_US
dc.relation.ispartofPharmaceuticalsen_US
dc.subjectcognitionen_US
dc.subjectcytokinesen_US
dc.subjectdrug developmenten_US
dc.subjectkynurenine pathwayen_US
dc.subjectserotoninen_US
dc.titleTryptophan Challenge in Healthy Controls and People with Schizophrenia: Acute Effects on Plasma Levels of Kynurenine, Kynurenic Acid and 5-Hydroxyindoleacetic Acid.en_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ph15081003
dc.identifier.pmid36015151
dc.source.journaltitlePharmaceuticals (Basel, Switzerland)
dc.source.volume15
dc.source.issue8
dc.source.countrySwitzerland


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