Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C

Background: Major depression is a frequent adverse effect of interferon-alpha (IFN-alpha) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-alpha-induced depression, no pharmacogenetic study has investigated Whether variation in the IDO gene modifies vulnerability to this adverse effect.Methods: A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpatient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-alpha plus ribavirin therapy. Genomic DNA of individuals was extracted from venous blood. Three IDO single-nucleotide polymorphisms (SNPs) were genotyped (rs3824259; rs10089084 and rs35099072).Results: MINI indicated that 21.3% of the sample met criteria for a major depressive episode during the course of IFN-alpha therapy. No association with the diagnosis of a major depressive episode during the course of IFN-alpha therapy was observed genotype or allele-wise (p > 0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-alpha-related depression (p 0.05).Conclusions: Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-alpha-related depression in the Brazilian population. Interferon-alpha-related depression may impose persistent psychopathology on at least 15% of the depressed patients even 2 years after antiviral therapy termination. the cross-sectional design is a limitation of our study, predisposing memory bias. Prospective pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-alpha-induced depression. (C) 2011 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Bahia, Sch Med, Dept Neurosci & Mental Hlth, BR-41170290 Salvador, BA, BrazilUniv Fed Bahia, Univ Hosp, Psychiat Serv, BR-41170290 Salvador, BA, BrazilUniversidade Federal de São Paulo, Sch Med, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Inst Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Dept Psychobiol, São Paulo, BrazilUniv Fed Bahia, Sch Med, Dept Gastroenterol, BR-41170290 Salvador, BA, BrazilUniversidade Federal de São Paulo, Sch Med, Hepatitis Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Hosp São Paulo, São Paulo, BrazilHarvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USAUniversidade Federal de São Paulo, Sch Med, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Inst Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Hepatitis Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, Hosp São Paulo, São Paulo, BrazilCNPq: 471592/2008-0CNPq: 142262/2008-0Web of Scienc