Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C
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2011-10-01
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Almeida, Amanda Cristina Galvão Oliveira de [UNIFESP]
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]
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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.
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Brain Behavior and Immunity. San Diego: Academic Press Inc Elsevier Science, v. 25, n. 7, p. 1491-1497, 2011.