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Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity

The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its ro...

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Autores principales: Viviani, Roberto, Messina, Irene, Bosch, Julia E., Dommes, Lisa, Paul, Anna, Schneider, Katharina L., Scholl, Catharina, Stingl, Julia C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539151/
https://www.ncbi.nlm.nih.gov/pubmed/33024081
http://dx.doi.org/10.1038/s41398-020-01020-z
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author Viviani, Roberto
Messina, Irene
Bosch, Julia E.
Dommes, Lisa
Paul, Anna
Schneider, Katharina L.
Scholl, Catharina
Stingl, Julia C.
author_facet Viviani, Roberto
Messina, Irene
Bosch, Julia E.
Dommes, Lisa
Paul, Anna
Schneider, Katharina L.
Scholl, Catharina
Stingl, Julia C.
author_sort Viviani, Roberto
collection PubMed
description The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data, while N = 415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate.
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spelling pubmed-75391512020-10-19 Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity Viviani, Roberto Messina, Irene Bosch, Julia E. Dommes, Lisa Paul, Anna Schneider, Katharina L. Scholl, Catharina Stingl, Julia C. Transl Psychiatry Article The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data, while N = 415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate. Nature Publishing Group UK 2020-10-06 /pmc/articles/PMC7539151/ /pubmed/33024081 http://dx.doi.org/10.1038/s41398-020-01020-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Viviani, Roberto
Messina, Irene
Bosch, Julia E.
Dommes, Lisa
Paul, Anna
Schneider, Katharina L.
Scholl, Catharina
Stingl, Julia C.
Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
title Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
title_full Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
title_fullStr Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
title_full_unstemmed Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
title_short Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
title_sort effects of genetic variability of cyp2d6 on neural substrates of sustained attention during on-task activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539151/
https://www.ncbi.nlm.nih.gov/pubmed/33024081
http://dx.doi.org/10.1038/s41398-020-01020-z
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