title: Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.
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.
authors: Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London WC1N 3AZ, UK.
authors: Takamitsu
authors: T
authors: Watanabe
authors: Department of Neuropsychiatry Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Takeshi
authors: T
authors: Otowa
authors: Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo 173-8610, Japan.
authors: Osamu
authors: O
authors: Abe
authors: Disability Services Office.
authors: Hitoshi
authors: H
authors: Kuwabara
authors: Department of Neuropsychiatry Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Yuta
authors: Y
authors: Aoki
authors: Department of Neuropsychiatry Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Tatsunobu
authors: T
authors: Natsubori
authors: Department of Radiology Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors: Hidemasa
authors: H
authors: Takao
authors: Department of Neuropsychiatry Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Chihiro
authors: C
authors: Kakiuchi
authors: Department of Psychiatry Fujita Health University School of Medicine, Aichi 470-1192, Japan.
authors: Kenji
authors: K
authors: Kondo
authors: Department of Psychiatry Fujita Health University School of Medicine, Aichi 470-1192, Japan.
authors: Masashi
authors: M
authors: Ikeda
authors: Department of Psychiatry Fujita Health University School of Medicine, Aichi 470-1192, Japan.
authors: Nakao
authors: N
authors: Iwata
authors: Department of Neuropsychiatry Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Kiyoto
authors: K
authors: Kasai
authors: Department of Physical and Health Education Graduate School of Education, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Tsukasa
authors: T
authors: Sasaki
authors: Department of Neuropsychiatry Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.|Department of Psychiatry Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City 431-3192, Japan.
authors: Hidenori
authors: H
authors: Yamasue
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000483:Alleles; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000069550:Machine Learning; D008297:Male; D010121:Oxytocin / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018045:Receptors, Oxytocin / Q000235:genetics*; D012919:Social Behavior; D055815:Young Adult
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin
keywords: imaging genetics; neuropeptide; pervasive developmental disorder; pharmacogenetics; randomized clinical trial; support vector machine