title: Interferon-gamma (+874) T/A genotypes and risk of IFN-alpha-induced depression.
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.
authors.affiliation: Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA. goxenkrug@tuftsmedicalcenter.org
authors.forename: G
authors.initials: G
authors.lastname: Oxenkrug
authors.forename: M
authors.initials: M
authors.lastname: Perianayagam
authors.forename: D
authors.initials: D
authors.lastname: Mikolich
authors.forename: P
authors.initials: P
authors.lastname: Requintina
authors.forename: L
authors.initials: L
authors.lastname: Shick
authors.forename: R
authors.initials: R
authors.lastname: Ruthazer
authors.forename: D
authors.initials: D
authors.lastname: Zucker
authors.forename: P
authors.initials: P
authors.lastname: Summergrad
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects*; D003863:Depression / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007371:Interferon-gamma