Journal
PSYCHIATRY AND CLINICAL NEUROSCIENCES
Volume 62, Issue 5, Pages 597-602Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1440-1819.2008.01854.x
Keywords
3-hydroxykynurenine; depression; interferon-alpha; kynurenine; kynurenic acid; neurotoxicity; quinolinic acid
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Funding
- Foundation Nuts OHRA
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Aims: Immunotherapy with interferon-alpha (IFN-alpha) 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-alpha 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-alpha-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-alpha 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-alpha-based immunotherapy, is neither supported nor rejected.
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