Journal
MOLECULAR PSYCHIATRY
Volume 15, Issue 4, Pages 393-403Publisher
SPRINGERNATURE
DOI: 10.1038/mp.2009.116
Keywords
indoleamine 2,3-dioxygenase; kynurenine; quinolinic acid; kynurenic acid; cytokines; depression
Funding
- National Institutes of Health [K23 MH064619, R01 MH070553, R01 MH 71349, R01 MH 079829, R01 AG 029573, K05 MH069124, R01 HL073921, T32 MH020018]
- Clinical and Translational Science Award program [UL1 RR025008]
- General Clinical Research Center program [M01 RR0039]
- National Institutes of Health, National Center for Research Resources
Ask authors/readers for more resources
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 similar to 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 significant increases in CSF QUIN and KA. Despite significant decreases in peripheral blood TRP, IFN-alpha had no effect on CSF TRP concentrations. Increases in CSF KYN and QUIN were correlated with increased CSF IFN-alpha, soluble tumor necrosis factor-alpha receptor 2 and monocyte chemoattractant protein-1 as well as increased depressive symptoms. In conclusion, peripheral administration of IFN-alpha activated IDO in concert with central cytokine responses, resulting in increased brain KYN and QUIN, which correlated with depressive symptoms. Molecular Psychiatry (2010) 15, 393-403; doi: 10.1038/mp.2009.116; published online 17 November 2009
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available