title: 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-α) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-α-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-α 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-α therapy. No association with the diagnosis of a major depressive episode during the course of IFN-α therapy was observed genotype or allele-wise (p>0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-α-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-α-related depression (p>0.05).
  
  
  CONCLUSIONS
  Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-α-related depression in the Brazilian population. Interferon-α-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-α-induced depression.
authors.affiliation: Department of Neurosciences and Mental Health, Medical School, Universidade Federal da Bahia, Bahia, Brazil. amandacgalvao@yahoo.com.br
authors.forename: Amanda
authors.initials: A
authors.lastname: Galvão-de Almeida
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Quarantini
authors.forename: Aline S
authors.initials: AS
authors.lastname: Sampaio
authors.forename: André C
authors.initials: AC
authors.lastname: Lyra
authors.forename: Carmen Lívia
authors.initials: CL
authors.lastname: Parise
authors.forename: Raymundo
authors.initials: R
authors.lastname: Paraná
authors.forename: Irismar R
authors.initials: IR
authors.lastname: de Oliveira
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
authors.forename: Angela
authors.initials: A
authors.lastname: Miranda-Scippa
authors.forename: Camila
authors.initials: C
authors.lastname: Guindalini
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001938:Brazil; D003430:Cross-Sectional Studies; D003863:Depression / Q000139:chemically induced / Q000235:genetics; D003866:Depressive Disorder / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha; D012254:Ribavirin