Interferon-gamma (+874) T/A genotypes and risk of IFN-alpha-induced depression

J Neural Transm (Vienna). 2011 Feb;118(2):271-4. doi: 10.1007/s00702-010-0525-1. Epub 2010 Dec 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / adverse effects*
  • Depression / chemically induced*
  • Depression / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Hepatitis C / drug therapy
  • Humans
  • Interferon-alpha / adverse effects*
  • Interferon-gamma / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Interferon-gamma