The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-α: relationship to CNS immune responses and depression
Open accessAbstract
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 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.
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“cytokines have been found to reduce levels of serotonin and possibly other related neurotransmitters by decreasing the availability of its serotonin precursor, an essential amino acid called tryptophan”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Raison et al., 2010
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“which may be attributed to the rapid metabolism of KYN once it is produced [47].”
From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [47]
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“Activation of the enzyme indoleamine 2,3-dioxygenase (IDO) is also believed to be involved in cytokine-induced neurotransmitter alterations, in part by diverting the metabolism of tryptophan (the primary amino acid precursor of serotonin) into kynurenine, a compound that can be converted into the neurotoxic metabolite quinolinic acid by activated microglia and infiltrating monocytes and macrophage”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [76]
In the citing paper
“other studies have suggested that increased kynurenine levels without a decrease in tryptophan levels could also lead to depressive-like behavior in both animal models and human subjects (Raison et al., 2010).”
From A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder (2014) · cites this paper as Raison et al., 2010
In the citing paper
“current results are promising and show altered levels of proinflammatory biomarkers in CSF samples of depressed patients relative to healthy controls (Raison et al., 2010).”
From A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder (2014) · cites this paper as Raison et al., 2010
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From inflammation to sickness and depression: when the immune system subjugates the brain
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Self-citationInflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
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Sorted by citations
The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942
Self-citationSlavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
“Finally, cytokines have been found to reduce levels of serotonin and possibly other related neurotransmitters by decreasing the availability of its serotonin precursor, an essential amino acid called tryptophan (Konsman, Parnet, & Dantzer, 2002; Mattson, Maudsley, & Martin, 2004; Raison et al., 2010; Schwarcz, Bruno,…”
BackgroundThe Bidirectional Relationship of Depression and Inflammation: Double Trouble
Beurel, E., Toups, M., & Nemeroff, C. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.002 · Cited by 2,136
Serotonin, tryptophan metabolism and the brain-gut-microbiome axis
O’Mahony, S. M., Clarke, G., Borre, Y. E., Dinan, T. G., & Cryan, J. F. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.07.027 · Cited by 2,012
Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530
Metadata
- Authors
- Raison, C. L., Dantzer, R., Kelley, K. W., Lawson, M. A., Woolwine, B. J., Vogt, G., Spivey, J. R., Saito, K., & Miller, A. H.
- Affiliations
- Emory University (US)
- University of Illinois Urbana-Champaign (US)
- Kyoto University (JP)
- Corresponding author
- Miller, A H
- Venue
- Molecular Psychiatry
- Published
- 2009-11-17
- Volume
- 15
- Issue
- 4
- Pages
- 393-403
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2844942
- OpenAlex
- W1973172818
- Cited by
- 630
- References
- 73
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 35 · 2023: 30 · 2022: 36 · 2021: 45 · 2020: 50 · 2019: 36 · 2018: 48 · 2017: 36 · 2016: 40 · 2015: 57 · 2014: 37 · 2013: 38 · 2012: 49
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Institute on Aging (R01AG029573)
- National Heart, Lung, and Blood Institute (R01HL073921)
- National Institute of Mental Health (R01MH079829, R01MH083746, R01MH071349, K23MH064619, T32MH020018, R01MH070553, K05MH069124)
- National Center for Research Resources (UL1RR025008, M01RR000039)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- interferon-alpha, kynurenine, quinolinic acid, kynurenic acid, tryptophan metabolism, indoleamine 2,3-dioxygenase, cerebrospinal fluid, depressive symptoms, hepatitis C, MCP-1, neuroinflammation
- MeSH terms
- Adult, Antiviral Agents, Chromatography, High Pressure Liquid, Depression, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis C, Humans, Kynurenine, Longitudinal Studies, Male, Middle Aged, Ribavirin, Statistics as Topic, Tryptophan, Cytokines, Interferon-alpha, Quinolinic Acid, Chemokine CCL2, Receptors, Tumor Necrosis Factor, Type II
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