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

Abstract

Background: Major depression is a frequent adverse effect of interferon-alpha (IFN-a) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-a-induced depression, no pharmacogenetic study has investigated whether variation in the IDO gene mod-ifies vulnerability to this adverse effect. Methods: A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpa-tient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-a 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-a therapy. No association with the diagnosis of a major depressive episode during the course of IFN-a therapy was observed genotype or allele-wise (p > 0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-a-related depression (p < 0.005). However, gender, age, route of infection, result of the antiviral treatment, past history of substance use disorders, depression or any other psychiatric disorder showed no association with IFN-a-related depression (p > 0.05). Conclusions: Our results suggest no influence of the variants in the IDO gene and the diagnosis of inter- feron-a-related depression in the Brazilian population. Interferon-a-related depression may impose per-sistent 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. Prospec- tive pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-a-induced depression.