Catechol-O-methyltransferase Val158Met polymorphism is associated with somatosensory amplification and nocebo responses
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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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The basic psychological mechanisms underlying the formation of negative expectations and nocebo effects are anticipation of and information about negative outcomes, prior lack of therapeutic effectiveness, and observation of other patients' pain worsening.
“The basic psychological mechanisms underlying the formation of negative expectations and thus, nocebo effects, are anticipation of and information about negative outcomes,34,76 prior lack of therapeutic effectiveness,33,34 and observation of other patients' pain worsening.42,60,74,77,78”
From Nocebo and pain: an overview of the psychoneurobiological mechanisms (2017) · cites this paper as [77]
Catastrophizing, an important psychological factor for pain management therapies, was found to be relevant for nocebo effects.
“Catastrophizing, an important psychological factor for pain management therapies, was also found to be relevant for nocebo effects.77”
From Nocebo and pain: an overview of the psychoneurobiological mechanisms (2017) · cites this paper as [77]
In a different study, the same research group found that the nocebo response was positively associated with pain catastrophizing.
“In a different study, the same research group found that the nocebo response was positively associated with pain catastrophizing.77”
From Nocebo and pain: an overview of the psychoneurobiological mechanisms (2017) · cites this paper as [77]
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Dusch, M. (2021) · AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie · doi:10.1055/a-1188-2591
Dusch, M. (2021) · AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie
Modalities and Dimensions of Interoception
Ferentzi, E. (2019) · Eötvös Loránd Tudományegyetem · doi:10.15476/elte.2019.045
Mitsikostas, D. D. (2023) · Oxford University Press eBooks · doi:10.1093/med/9780197645444.003.0013
Manaï, M., van Middendorp, H., van der Pol, J. A., Allaart, C. F., Dusseldorp, E., Veldhuijzen, D. S., Huizinga, T. W. J., & Evers, A. W. M. (2024) · Pharmaceuticals · doi:10.3390/ph17010110
van Lennep, J. P. A., van Middendorp, H., Leong, O. V., Kloet, S. L., Vossen, R. H. A. M., Heyman, T., & Evers, A. W. M. (2025) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2025-0029
- Authors
- Wendt, L., Albring, A., Benson, S., Engler, H., Engler, A., Hinney, A., Rief, W., Witzke, O., & Schedlowski, M.
- Affiliations
- Essen University Hospital (DE)
- Philipps University of Marburg (DE)
- Corresponding author
- Schedlowski, Manfred
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-09-15
- Volume
- 9
- Issue
- 9
- Pages
- e107665
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4164653
- OpenAlex
- W1985370266
- Cited by
- 47
- References
- 52
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 2
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (SCHE 341/17-1, SCHE 341/17-2, FOR1328)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nocebo effect, catechol-O-methyltransferase, COMT Val158Met polymorphism, somatosensory amplification, placebo response, adverse drug reactions, immunosuppressants, medication beliefs, interindividual variability
- MeSH terms
- Adolescent, Adult, Catechol O-Methyltransferase, Genotype, Humans, Immunosuppressive Agents, Male, Polymorphism, Single Nucleotide, Genetic Association Studies, Nocebo Effect
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