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Title
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Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-: course and relationship with psychiatric status
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Author
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Abstract
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| Aims: Immunotherapy with interferon-á (IFN-á) is associated with psychiatric side-effects, including depression. One of the putative pathways underlying these psychiatric side-effects involves tryptophan (TRP) metabolism. Cytokines including IFN-á induce the enzyme indoleamine 2,3-dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5-HT). In addition, the production of neurotoxic metabolites of KYN such as 3-hydroxykynurenine and quinolinic acid (QA) might increase and contribute to IFN-á-induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties. Methods: In a group of 24 patients treated with standard IFN-á for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months. Results: No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN. Conclusions: The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side-effects of IFN-á-based immunotherapy, is neither supported nor rejected. |
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Language
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English
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Source (journal)
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Psychiatry and clinical neurosciences. - Tokyo
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Publication
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Tokyo
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2008
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ISSN
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1323-1316
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DOI
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10.1111/J.1440-1819.2008.01854.X
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Volume/pages
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62
:5
(2008)
, p. 597-602
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ISI
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000259685000016
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Full text (Publisher's DOI)
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