A step for precise medicine: genetic patterns indicate efficacy of oxytocin on autistic social behaivours

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.

Anatomical imbalance in autistic brains

Watanabe, T., & Rees, G. (2016). Anatomical imbalance between cortical networks in autism. Scientific Reports, 6, 31114. http://doi.org/10.1038/srep31114. 

 

 

Core symptoms of autism spectrum disorder (ASD) consist of socio-communicational deficits and repetitive, restricted behaviours. Although the neuroanatomy underlying these two symptoms has been studied, the biological mechanisms that allow these two seemingly irrelevant behavioural characteristics to coexist in a single developmental disorder remains unclear.

In this study using open anatomical neuroimaging data of high-functioning males with ASD and age-/sex-/IQ-matched controls, we found that atypical balance of grey matter volumes (GMV) between three large-scale cortical brain networks can be a key biological mechanism underlying such integration and segregation of these distinct symptoms of ASD.

We identified age-related atypical increases in relative GMVs of the regions constituting auditory and visual networks, and an age-associated aberrant decrease in relative GMV of fronto-parietal network (FPN) regions in ASD children. In addition, the atypically enlarged relative GMV of the auditory network in ASD adults was associated with the severity of their socio-communicational deficits, and that of visual network was correlated with cognitive inflexibility. Moreover, the atypical decrease in relative GMV of FPN was related to both of the two core symptoms.

These observations suggest that disproportionate undergrowth of FPN may be a common anatomical basis for the two dissociable and seemingly heterogeneous core symptoms of ASD, and relative overgrowth of the two different sensory networks may selectively underlie the different autistic symptoms.