CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression.

Molecular Psychiatry
Charles L RaisonAndrew H Miller

Abstract

Cytokine-induced activation of indoleamine 2,3-dioxygenase (IDO) catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA). QUIN and KA are neuroactive and may contribute to the behavioral changes experienced by some patients during exposure to inflammatory stimuli such as interferon (IFN)-alpha. A relationship between depressive symptoms and peripheral blood TRP, KYN and KA during treatment with IFN-alpha has been described. However, whether peripheral blood changes in these IDO catabolites are manifest in the brain and whether they are related to central nervous system cytokine responses and/or behavior is unknown. Accordingly, TRP, KYN, QUIN and KA were measured in cerebrospinal fluid (CSF) and blood along with CSF concentrations of relevant cytokines, chemokines and soluble cytokine receptors in 27 patients with hepatitis C after approximately 12 weeks of either treatment with IFN-alpha (n=16) or no treatment (n=11). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. IFN-alpha significantly increased peripheral blood KYN, which was accompanied by marked increases in CSF KYN. Increased CSF KYN was in turn associated with ...Continue Reading

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Citations

Aug 9, 2011·Inflammatory Bowel Diseases·Nitin K GuptaMatthew A Ciorba
Jul 26, 2011·Journal of Neural Transmission·Vilma GabbayLeonard Liebes
Sep 20, 2011·Current Psychiatry Reports·Charles L Raison, Andrew H Miller
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Sep 16, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ebrahim HaroonAndrew H Miller
Nov 11, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Patricia A ZunszainCarmine M Pariante
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Methods Mentioned

BETA
blood collection
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

SPSS
ESA EZ Chrom SI

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