Association of a polymorphism in the indoleamine-2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C

A. K. Smith, J. S. Simon, E. L. Gustafson, S. Noviello, J. F. Cubells, M. P. Epstein, D. J. Devlin, P. Qiu, J. K. Albrecht, C. A. Brass, M. S. Sulkowski, J. G. McHutchinson, A. H. Miller

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Interferon (IFN)-α treatment for infectious diseases and cancer is associated with significant depressive symptoms that can limit therapeutic efficacy. Multiple mechanisms have been implicated in IFN-α-induced depression including immune, neuroendocrine and neurotransmitter pathways. To further explore mechanisms of IFN-α-induced depression and establish associated genetic risk factors, single nucleotide polymorphisms in genes encoding proteins previously implicated in IFN-α-induced depression were explored in two self-reported ethnic groups, Caucasians (n=800) and African Americans (n=232), participating in a clinical trial on the impact of three pegylated IFN-α treatment regimens on sustained viral response in patients with chronic hepatitis C. Before treatment, all subjects were free of psychotropic medications and had a score ≤20 on the Center for Epidemiologic Studies Depression Scale (CES-D), which was used to assess depressive symptom severity throughout the study. In Caucasians, a polymorphism (rs9657182) in the promoter region of the gene encoding indoleamine-2,3-dioxygenase (IDO1) was found to be associated with moderate or severe IFN-α-induced depressive symptoms (CES-D20) at 12 weeks of IFN-α treatment (P=0.0012, P<0.05 corrected). Similar results were obtained for treatment weeks 24, 36 and 48. In subjects homozygous for the risk allele (CC, n=150), the odds ratio for developing moderate or severe depressive symptoms at treatment week 12 was 2.91 (confidence interval: 1.48-5.73) compared with TT homozygotes (n=270). rs9657182 did not predict depression in African Americans, who exhibited a markedly lower frequency of the risk allele at this locus. The findings in Caucasians further support the notion that IDO has an important role in cytokine-induced behavioral changes.

Original languageEnglish (US)
Pages (from-to)781-789
Number of pages9
JournalMolecular psychiatry
Issue number8
StatePublished - Aug 2012


  • cytokines
  • depression
  • genes
  • indoleamine-2,3-dioxygenase
  • interferon-α
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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