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Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach

Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and border...

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Autores principales: Chen, F S, Kumsta, R, Dvorak, F, Domes, G, Yim, O S, Ebstein, R P, Heinrichs, M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930136/
https://www.ncbi.nlm.nih.gov/pubmed/26506050
http://dx.doi.org/10.1038/tp.2015.163
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author Chen, F S
Kumsta, R
Dvorak, F
Domes, G
Yim, O S
Ebstein, R P
Heinrichs, M
author_facet Chen, F S
Kumsta, R
Dvorak, F
Domes, G
Yim, O S
Ebstein, R P
Heinrichs, M
author_sort Chen, F S
collection PubMed
description Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917–rs2268498–rs4564970–rs237897–rs2268495–rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration.
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spelling pubmed-49301362016-07-14 Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach Chen, F S Kumsta, R Dvorak, F Domes, G Yim, O S Ebstein, R P Heinrichs, M Transl Psychiatry Original Article Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917–rs2268498–rs4564970–rs237897–rs2268495–rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration. Nature Publishing Group 2015-10 2015-10-27 /pmc/articles/PMC4930136/ /pubmed/26506050 http://dx.doi.org/10.1038/tp.2015.163 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Chen, F S
Kumsta, R
Dvorak, F
Domes, G
Yim, O S
Ebstein, R P
Heinrichs, M
Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
title Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
title_full Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
title_fullStr Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
title_full_unstemmed Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
title_short Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
title_sort genetic modulation of oxytocin sensitivity: a pharmacogenetic approach
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930136/
https://www.ncbi.nlm.nih.gov/pubmed/26506050
http://dx.doi.org/10.1038/tp.2015.163
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