Published in:
01-02-2011 | Biological Psychiatry - Short Communication
Interferon-gamma (+874) T/A genotypes and risk of IFN-alpha-induced depression
Authors:
G. Oxenkrug, M. Perianayagam, D. Mikolich, P. Requintina, L. Shick, R. Ruthazer, D. Zucker, P. Summergrad
Published in:
Journal of Neural Transmission
|
Issue 2/2011
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Abstract
Depression is a frequent side effect of interferon (IFN)-alpha therapy of hepatitis C (HCV) and is of great relevance with regard to adherence, compliance, and premature therapy discontinuation. There are no reliable tests to identify patients-at-risk for the development of IFN-alpha induced depression. We retrospectively studied distribution of IFN-gamma (IFNG) (+874) T/A genotypes in 170 Caucasian HCV patients treated by IFN-alpha. Distribution of IFNG (+874) genotypes was different between depressed and not depressed subjects with more TA and less AA carriers among depressed than among not depressed subjects (P = 0.003). Carriers with at least one T allele were more frequent among depressed than among not depressed patients (P = 0.003). Our results suggest that presence of high producer (T) alleles might be a genetic risk factor for the development of IFN-alpha-induced depression. Assessment of IFNG (+874) genotypes might help to identify patients-at-risk for IFN-alpha-induced depression. IFNG and IFN-alpha transcriptionally induce indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme of the kynurenine (KYN) pathway of tryptophan (TRY) metabolism. IFN-induced up-regulation of IDO triggers depression by shifting TRY metabolism from formation of serotonin to production of neuroactive kynurenines. TRY–KYN pathway might be a new target for pharmacological prevention and treatment of IFN-alpha-induced psychiatric complications.