Watanabe, T., Otowa, T., Abe, O., Kuwabara, H., Aoki, Y., Natsubori, T., et al. (2016). Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism. Social Cognitive and Affective Neuroscience, nsw150. http://doi.org/10.1093/scan/nsw150
Oxytocin and its receptor (OXTR) are known to be deeply associated with autism spectrum disorder (ASD), a prevalent neurodevelopmental disorder with impaired social communication and interactions as its core symptoms. A line of genetics studies have identified associations between ASD and more than a dozen single-nucleotide polymorphisms (SNPs) in OXTR, and clinical trials have shown a possibility that administration of oxytocin could behaviorally and neurally mitigate its social symptoms.
However, despite these biologically and clinically crucial relationships, the neurobiological functionality of OXTR SNPs in ASD is poorly understood, and hence, the crucial OXTR SNPs determining oxytocin efficacy in ASD are also unknown.
Here, to address this issue, we have applied a newly-developed machine-learning-based algorithm to newly-obtained genetic information of ASD participants, whose sample size was determined based on a power analysis a priori.
We have found that specific OXTR SNPs have functionally dissociable influences on behavioral and neural responses to oxytocin in ASD. In particular, ASD risk alleles in the two most prominent OXTR SNPs (rs53576 and rs2254298) were suggested to have opposite neurobiological effects on oxytocin-related neural systems in ASD. Furthermore, we have demonstrated that allelic information in such specific SNP sets enables accurate prediction of behavioral, neural, and neurochemical responses to oxytocin for each individual with ASD.
These results provide novel biological understandings of functionality of OXTR SNPs in ASD, and the current analysis approach is widely applicable to future investigations on gene-endophenotype relationships.
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