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, Mark Sulkowski, J. G. McHutchinson, A. H. Miller

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
Pages (from-to)781-789
Number of pages9
JournalMolecular Psychiatry
Volume17
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Chronic Hepatitis C
Interferons
Depression
Genes
Therapeutics
Ethnic Groups
Genetic Promoter Regions
African Americans
Single Nucleotide Polymorphism
Communicable Diseases
Neurotransmitter Agents
Epidemiologic Studies
Clinical Trials

Keywords

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

ASJC Scopus subject areas

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

Cite this

Smith, A. K., Simon, J. S., Gustafson, E. L., Noviello, S., Cubells, J. F., Epstein, M. P., ... Miller, A. H. (2012). Association of a polymorphism in the indoleamine-2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C. Molecular Psychiatry, 17(8), 781-789. https://doi.org/10.1038/mp.2011.67

Association of a polymorphism in the indoleamine-2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C. / Smith, A. K.; Simon, J. S.; Gustafson, E. L.; Noviello, S.; Cubells, J. F.; Epstein, M. P.; Devlin, D. J.; Qiu, P.; Albrecht, J. K.; Brass, C. A.; Sulkowski, Mark; McHutchinson, J. G.; Miller, A. H.

In: Molecular Psychiatry, Vol. 17, No. 8, 08.2012, p. 781-789.

Research output: Contribution to journalArticle

Smith, AK, Simon, JS, Gustafson, EL, Noviello, S, Cubells, JF, Epstein, MP, Devlin, DJ, Qiu, P, Albrecht, JK, Brass, CA, Sulkowski, M, McHutchinson, JG & Miller, AH 2012, 'Association of a polymorphism in the indoleamine-2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C', Molecular Psychiatry, vol. 17, no. 8, pp. 781-789. https://doi.org/10.1038/mp.2011.67
Smith, A. K. ; Simon, J. S. ; Gustafson, E. L. ; Noviello, S. ; Cubells, J. F. ; Epstein, M. P. ; Devlin, D. J. ; Qiu, P. ; Albrecht, J. K. ; Brass, C. A. ; Sulkowski, Mark ; McHutchinson, J. G. ; Miller, A. H. / Association of a polymorphism in the indoleamine-2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C. In: Molecular Psychiatry. 2012 ; Vol. 17, No. 8. pp. 781-789.
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