Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

Hdl Handle:
http://hdl.handle.net/10147/200770
Title:
Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.
Authors:
Bull, S J; Huezo-Diaz, P; Binder, E B; Cubells, J F; Ranjith, G; Maddock, C; Miyazaki, C; Alexander, N; Hotopf, M; Cleare, A J; Norris, S; Cassidy, E; Aitchison, K J; Miller, A H; Pariante, C M
Affiliation:
King's College London, Section and Laboratory of Stress, Psychiatry and Immunology, Institute of Psychiatry, London, UK.
Citation:
Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. 2009, 14 (12):1095-104 Mol. Psychiatry
Journal:
Molecular psychiatry
Issue Date:
Dec-2009
URI:
http://hdl.handle.net/10147/200770
DOI:
10.1038/mp.2008.48
PubMed ID:
18458677
Abstract:
Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.
Item Type:
Article
Language:
en
Description:
Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.
MeSH:
Adult; Antiviral Agents; Cohort Studies; Depression; Fatigue; Female; Gene Frequency; Genotype; Hepatitis C, Chronic; Humans; Interferon Type I; Interleukin-6; Male; Middle Aged; Polymorphism, Genetic; Psychiatric Status Rating Scales; Recombinant Proteins; Ribavirin; Serotonin Plasma Membrane Transport Proteins
ISSN:
1476-5578

Full metadata record

DC FieldValue Language
dc.contributor.authorBull, S Jen
dc.contributor.authorHuezo-Diaz, Pen
dc.contributor.authorBinder, E Ben
dc.contributor.authorCubells, J Fen
dc.contributor.authorRanjith, Gen
dc.contributor.authorMaddock, Cen
dc.contributor.authorMiyazaki, Cen
dc.contributor.authorAlexander, Nen
dc.contributor.authorHotopf, Men
dc.contributor.authorCleare, A Jen
dc.contributor.authorNorris, Sen
dc.contributor.authorCassidy, Een
dc.contributor.authorAitchison, K Jen
dc.contributor.authorMiller, A Hen
dc.contributor.authorPariante, C Men
dc.date.accessioned2012-01-06T15:41:54Z-
dc.date.available2012-01-06T15:41:54Z-
dc.date.issued2009-12-
dc.identifier.citationFunctional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. 2009, 14 (12):1095-104 Mol. Psychiatryen
dc.identifier.issn1476-5578-
dc.identifier.pmid18458677-
dc.identifier.doi10.1038/mp.2008.48-
dc.identifier.urihttp://hdl.handle.net/10147/200770-
dc.descriptionDepression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.en
dc.description.abstractDepression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.-
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshAntiviral Agents-
dc.subject.meshCohort Studies-
dc.subject.meshDepression-
dc.subject.meshFatigue-
dc.subject.meshFemale-
dc.subject.meshGene Frequency-
dc.subject.meshGenotype-
dc.subject.meshHepatitis C, Chronic-
dc.subject.meshHumans-
dc.subject.meshInterferon Type I-
dc.subject.meshInterleukin-6-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshPsychiatric Status Rating Scales-
dc.subject.meshRecombinant Proteins-
dc.subject.meshRibavirin-
dc.subject.meshSerotonin Plasma Membrane Transport Proteins-
dc.titleFunctional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.en
dc.typeArticleen
dc.contributor.departmentKing's College London, Section and Laboratory of Stress, Psychiatry and Immunology, Institute of Psychiatry, London, UK.en
dc.identifier.journalMolecular psychiatryen
dc.description.provinceMunster-

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