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

• Autor(a) principal: Almeida, Amanda Cristina Galvão Oliveira de [UNIFESP]
• Data de Publicação: 2011
• Outros Autores: Quarantini, Lucas de Castro [UNIFESP], Sampaio, Aline Santos [UNIFESP], Lyra, André Castro, Parise, Carmen Livia [UNIFESP], Paraná, Raymundo, Oliveira, Irismar Reis de, Koenen, Karestan C, Miranda-Scippa, Ângela Marisa de Aquino [UNIFESP], Guindalini, Camila [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1016/j.bbi.2011.06.001; http://repositorio.unifesp.br/handle/11600/34065
• topic: Interferon-alpha; Major depressive disorder; Hepatitis C; Genetic polymorphism; Pharmacogenetics; Substance-related disorders

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 < 0.005). 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 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.