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Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains k...

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Autores principales: Watanabe, Takamitsu, Otowa, Takeshi, Abe, Osamu, Kuwabara, Hitoshi, Aoki, Yuta, Natsubori, Tatsunobu, Takao, Hidemasa, Kakiuchi, Chihiro, Kondo, Kenji, Ikeda, Masashi, Iwata, Nakao, Kasai, Kiyoto, Sasaki, Tsukasa, Yamasue, Hidenori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390696/
https://www.ncbi.nlm.nih.gov/pubmed/27798253
http://dx.doi.org/10.1093/scan/nsw150
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author Watanabe, Takamitsu
Otowa, Takeshi
Abe, Osamu
Kuwabara, Hitoshi
Aoki, Yuta
Natsubori, Tatsunobu
Takao, Hidemasa
Kakiuchi, Chihiro
Kondo, Kenji
Ikeda, Masashi
Iwata, Nakao
Kasai, Kiyoto
Sasaki, Tsukasa
Yamasue, Hidenori
author_facet Watanabe, Takamitsu
Otowa, Takeshi
Abe, Osamu
Kuwabara, Hitoshi
Aoki, Yuta
Natsubori, Tatsunobu
Takao, Hidemasa
Kakiuchi, Chihiro
Kondo, Kenji
Ikeda, Masashi
Iwata, Nakao
Kasai, Kiyoto
Sasaki, Tsukasa
Yamasue, Hidenori
author_sort Watanabe, Takamitsu
collection PubMed
description Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs—including rs53576 and rs2254298—were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD.
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spelling pubmed-53906962017-05-01 Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism Watanabe, Takamitsu Otowa, Takeshi Abe, Osamu Kuwabara, Hitoshi Aoki, Yuta Natsubori, Tatsunobu Takao, Hidemasa Kakiuchi, Chihiro Kondo, Kenji Ikeda, Masashi Iwata, Nakao Kasai, Kiyoto Sasaki, Tsukasa Yamasue, Hidenori Soc Cogn Affect Neurosci Original Articles Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs—including rs53576 and rs2254298—were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. Oxford University Press 2016-10-19 /pmc/articles/PMC5390696/ /pubmed/27798253 http://dx.doi.org/10.1093/scan/nsw150 Text en © The Author(s) (2016). Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Watanabe, Takamitsu
Otowa, Takeshi
Abe, Osamu
Kuwabara, Hitoshi
Aoki, Yuta
Natsubori, Tatsunobu
Takao, Hidemasa
Kakiuchi, Chihiro
Kondo, Kenji
Ikeda, Masashi
Iwata, Nakao
Kasai, Kiyoto
Sasaki, Tsukasa
Yamasue, Hidenori
Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
title Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
title_full Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
title_fullStr Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
title_full_unstemmed Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
title_short Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
title_sort oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390696/
https://www.ncbi.nlm.nih.gov/pubmed/27798253
http://dx.doi.org/10.1093/scan/nsw150
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