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Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses

A large number of unwanted adverse events and symptoms reported by patients in clinical trials are not caused by the drug provided, since most of adverse events also occur in corresponding placebo groups. These nocebo effects also play a major role in drug discontinuation in clinical practice, negat...

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Autores principales: Wendt, Laura, Albring, Antje, Benson, Sven, Engler, Harald, Engler, Andrea, Hinney, Anke, Rief, Winfried, Witzke, Oliver, Schedlowski, Manfred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164653/
https://www.ncbi.nlm.nih.gov/pubmed/25222607
http://dx.doi.org/10.1371/journal.pone.0107665
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author Wendt, Laura
Albring, Antje
Benson, Sven
Engler, Harald
Engler, Andrea
Hinney, Anke
Rief, Winfried
Witzke, Oliver
Schedlowski, Manfred
author_facet Wendt, Laura
Albring, Antje
Benson, Sven
Engler, Harald
Engler, Andrea
Hinney, Anke
Rief, Winfried
Witzke, Oliver
Schedlowski, Manfred
author_sort Wendt, Laura
collection PubMed
description A large number of unwanted adverse events and symptoms reported by patients in clinical trials are not caused by the drug provided, since most of adverse events also occur in corresponding placebo groups. These nocebo effects also play a major role in drug discontinuation in clinical practice, negatively affecting treatment efficacy as well as patient adherence and compliance. Experimental and clinical data document a large interindividual variability in nocebo responses, however, data on psychological, biological or genetic predictors of nocebo responses are lacking. Thus, with an established paradigm of behaviorally conditioned immunosuppressive effects we analyzed possible genetic predictors for nocebo responses. We focused on the genetic polymorphisms in the catechol-O-methyltransferase (COMT) gene (Val158Met) and analyzed drug specific and general side effects before and after immunosuppressive medication and subsequent placebo intake in 62 healthy male subjects. Significantly more drug-specific as well as general side effects were reported from homozygous carriers of the Val158 variant during medication as well as placebo treatment compared to the other genotype groups. Val158/Val158 carriers also had significantly higher scores in the somatosensory amplification scale (SSAS) and the BMQ (beliefs about medicine questionnaire). Together these data demonstrate potential genetic and psychological variables predicting nocebo responses after drug and placebo intake, which might be utilized to minimize nocebo effects in clinical trials and medical practice.
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spelling pubmed-41646532014-09-19 Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses Wendt, Laura Albring, Antje Benson, Sven Engler, Harald Engler, Andrea Hinney, Anke Rief, Winfried Witzke, Oliver Schedlowski, Manfred PLoS One Research Article A large number of unwanted adverse events and symptoms reported by patients in clinical trials are not caused by the drug provided, since most of adverse events also occur in corresponding placebo groups. These nocebo effects also play a major role in drug discontinuation in clinical practice, negatively affecting treatment efficacy as well as patient adherence and compliance. Experimental and clinical data document a large interindividual variability in nocebo responses, however, data on psychological, biological or genetic predictors of nocebo responses are lacking. Thus, with an established paradigm of behaviorally conditioned immunosuppressive effects we analyzed possible genetic predictors for nocebo responses. We focused on the genetic polymorphisms in the catechol-O-methyltransferase (COMT) gene (Val158Met) and analyzed drug specific and general side effects before and after immunosuppressive medication and subsequent placebo intake in 62 healthy male subjects. Significantly more drug-specific as well as general side effects were reported from homozygous carriers of the Val158 variant during medication as well as placebo treatment compared to the other genotype groups. Val158/Val158 carriers also had significantly higher scores in the somatosensory amplification scale (SSAS) and the BMQ (beliefs about medicine questionnaire). Together these data demonstrate potential genetic and psychological variables predicting nocebo responses after drug and placebo intake, which might be utilized to minimize nocebo effects in clinical trials and medical practice. Public Library of Science 2014-09-15 /pmc/articles/PMC4164653/ /pubmed/25222607 http://dx.doi.org/10.1371/journal.pone.0107665 Text en © 2014 Wendt et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wendt, Laura
Albring, Antje
Benson, Sven
Engler, Harald
Engler, Andrea
Hinney, Anke
Rief, Winfried
Witzke, Oliver
Schedlowski, Manfred
Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses
title Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses
title_full Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses
title_fullStr Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses
title_full_unstemmed Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses
title_short Catechol-O-Methyltransferase Val158Met Polymorphism Is Associated with Somatosensory Amplification and Nocebo Responses
title_sort catechol-o-methyltransferase val158met polymorphism is associated with somatosensory amplification and nocebo responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164653/
https://www.ncbi.nlm.nih.gov/pubmed/25222607
http://dx.doi.org/10.1371/journal.pone.0107665
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