Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
Open accessAbstract
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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Several studies suggest that oxytocin effects on behavior and brain function are modulated by OXTR genotype.
“Several studies indeed suggest that oxytocin effects on behavior54–56 and brain function57–59 are modulated by OXTR genotype.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [59]
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- Authors
- 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.
- Affiliations
- University College London (GB)
- The University of Tokyo (JP)
- Nihon University (JP)
- Disability Services Office
- Fujita Health University (JP)
- Hamamatsu University (JP)
- Corresponding author
- Yamasue, Hidenori
- ORCID
- Venue
- Social Cognitive and Affective Neuroscience
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-10-19
- Volume
- 12
- Issue
- 3
- Pages
- 496-506
- ISSN
- 1749-5016 (ISSN-L)
- 1749-5024
- PMC
- PMC5390696
- OpenAlex
- W2536702549
- Cited by
- 54
- References
- 57
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 8 · 2017: 5
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Social Cognitive and Affective Neuroscience (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Grants-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science (26670535)
- Adaptable and Seamless Technology Transfer Program; the Centre of Innovation Program
- CREST from Japan Science and Technology Agency; Medicinal-Grant from Takeda Science Foundation
- Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science, and Technology
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- oxytocin receptor, autism spectrum disorder, intranasal oxytocin, rs53576, rs2254298, high-functioning adults, precision medicine
- MeSH terms
- Autism Spectrum Disorder, Machine Learning, Adolescent, Adult, Algorithms, Alleles, Genotype, Humans, Male, Oxytocin, Social Behavior, Genetic Variation, Receptors, Oxytocin, Polymorphism, Single Nucleotide, Young Adult
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