Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C

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 expl...

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Main Authors:	Smith, Alicia K., Simon, Jason S., Gustafson, Eric L., Noviello, Stephanie, Cubells, Joseph F., Epstein, Michael P., Devlin, David J., Qiu, Ping, Albrecht, Janice K., Brass, Clifford A., Sulkowski, Mark S., McHutchinson, John G., Miller, Andrew H.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179823/

id	pubmed-3179823
recordtype	oai_dc
spelling	pubmed-31798232013-01-01 Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C Smith, Alicia K. Simon, Jason S. Gustafson, Eric L. Noviello, Stephanie Cubells, Joseph F. Epstein, Michael P. Devlin, David J. Qiu, Ping Albrecht, Janice K. Brass, Clifford A. Sulkowski, Mark S. McHutchinson, John G. Miller, Andrew H. Article 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 2 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. Prior to 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-D >20) 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 (CI: 1.48–5.73) compared to 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 indoleamine-2,3-dioxygenase plays an important role in cytokine-induced behavioral changes. 2011-06-21 2012-07 /pmc/articles/PMC3179823/ /pubmed/21691274 http://dx.doi.org/10.1038/mp.2011.67 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Smith, Alicia K. Simon, Jason S. Gustafson, Eric L. Noviello, Stephanie Cubells, Joseph F. Epstein, Michael P. Devlin, David J. Qiu, Ping Albrecht, Janice K. Brass, Clifford A. Sulkowski, Mark S. McHutchinson, John G. Miller, Andrew H.
spellingShingle	Smith, Alicia K. Simon, Jason S. Gustafson, Eric L. Noviello, Stephanie Cubells, Joseph F. Epstein, Michael P. Devlin, David J. Qiu, Ping Albrecht, Janice K. Brass, Clifford A. Sulkowski, Mark S. McHutchinson, John G. Miller, Andrew H. Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C
author_facet	Smith, Alicia K. Simon, Jason S. Gustafson, Eric L. Noviello, Stephanie Cubells, Joseph F. Epstein, Michael P. Devlin, David J. Qiu, Ping Albrecht, Janice K. Brass, Clifford A. Sulkowski, Mark S. McHutchinson, John G. Miller, Andrew H.
author_sort	Smith, Alicia K.
title	Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C
title_short	Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C
title_full	Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C
title_fullStr	Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C
title_full_unstemmed	Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C
title_sort	association of a polymorphism in the indoleamine-2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis c
description	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 2 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. Prior to 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-D >20) 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 (CI: 1.48–5.73) compared to 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 indoleamine-2,3-dioxygenase plays an important role in cytokine-induced behavioral changes.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179823/
_version_	1611477263064236032

Association of a Polymorphism in the Indoleamine-2,3-Dioxygenase Gene and Interferon-α-Induced Depression in Patients with Chronic Hepatitis C

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