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

Takamitsu Watanabe, Takeshi Otowa, Osamu Abe, Hitoshi Kuwabara, Yuta Aoki, Tatsunobu Natsubori, Hidemasa Takao, Chihiro Kakiuchi, Kenji Kondo, Masashi Ikeda, Nakao Iwata, Kiyoto Kasai, Tsukasa Sasaki, Hidenori Yamasue

研究成果: Article

14 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)496-506
ページ数11
ジャーナルSocial Cognitive and Affective Neuroscience
12
発行部数3
DOI
出版物ステータスPublished - 01-01-2017

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Oxytocin Receptors
Oxytocin
Autistic Disorder
Single Nucleotide Polymorphism
Genes
Precision Medicine
Autism Spectrum Disorder
Alleles
Placebos
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience

これを引用

Watanabe, T., Otowa, T., Abe, O., Kuwabara, H., Aoki, Y., Natsubori, T., ... Yamasue, H. (2017). Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism. Social Cognitive and Affective Neuroscience, 12(3), 496-506. https://doi.org/10.1093/scan/nsw150
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. :: Social Cognitive and Affective Neuroscience. 2017 ; 巻 12, 番号 3. pp. 496-506.
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abstract = "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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Watanabe, T, Otowa, T, Abe, O, Kuwabara, H, Aoki, Y, Natsubori, T, Takao, H, Kakiuchi, C, Kondo, K, Ikeda, M, Iwata, N, Kasai, K, Sasaki, T & Yamasue, H 2017, 'Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism', Social Cognitive and Affective Neuroscience, 巻. 12, 番号 3, pp. 496-506. https://doi.org/10.1093/scan/nsw150

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.

:: Social Cognitive and Affective Neuroscience, 巻 12, 番号 3, 01.01.2017, p. 496-506.

研究成果: Article

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T1 - Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

AU - Watanabe, Takamitsu

AU - Otowa, Takeshi

AU - Abe, Osamu

AU - Kuwabara, Hitoshi

AU - Aoki, Yuta

AU - Natsubori, Tatsunobu

AU - Takao, Hidemasa

AU - Kakiuchi, Chihiro

AU - Kondo, Kenji

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Kasai, Kiyoto

AU - Sasaki, Tsukasa

AU - Yamasue, Hidenori

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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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