Watanabe, T;
Otowa, T;
Abe, O;
Kuwabara, H;
Aoki, Y;
Natsubori, T;
Takao, H;
... Yamasue, H; + view all
(2016)
Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.
Social Cognitive & Affective Neuroscience
, 12
(3)
pp. 496-506.
10.1093/scan/nsw150.
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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 remain unknown. 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.
| Type: | Article |
|---|---|
| Title: | Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/scan/nsw150 |
| Publisher version: | http://dx.doi.org/10.1093/scan/nsw150 |
| Language: | English |
| Additional information: | This is a pre-copyedited, author-produced version of an article accepted for publication in Social Cognitive & Affective Neuroscience following peer review. The version of record, Watanabe, T; Otowa, T; Abe, O; Kuwabara, H; Aoki, Y; Natsubori, T; Takao, H; (2016) Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism. Social Cognitive & Affective Neuroscience, is available online at: http://dx.doi.org/10.1093/scan/nsw150. |
| Keywords: | Imaging genetics, Neuropeptide, Pervasive developmental disorder, Pharmacogenetics, Randomized clinical trial, Support vector machine |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1528591 |
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