M12 - The Oxytocin Receptor Interacts with Autism Diagnosis To Predict Brain Activation In Response To The Eyes Test

Abstract

Background Autism is a highly heritable condition, and common variants explain approximately 50% of the genetic variance of autism. Individuals with autism typically have difficulties with social interactions, which may be due to altered social cognition. Variants in the Oxytocin Receptor (OXTR) have been implicated in both autism and social cognition. Functional neuroimaging studies on the brain’s response to social tasks in individuals with autism have yielded mixed findings. This may not be surprising as autism is a heterogeneous neurodevelopmental condition, with varied genetic and biological aetiologies. In the current study we combine genetics and functional neuroimaging to investigate the biological basis of differences in social cognition in autism. Methods Participants were adolescents (12-18 years old): 41 (11 females) were diagnosed with high-functioning autism or Asperger syndrome (autism group) and 33 (17 females) were typically developing (control group). Participants provided buccal DNA samples and these were genotyped for 7 Single Nucleotide Polymorphisms (SNPs) in the OXTR; of these, 2 had little variance in the sample and were excluded from further analysis. The remaining 5 SNPs were rs2254298, rs53576, rs2268491, rs2228485, and rs7632287. The participants were scanned using a Siemens 3-T TimTrio scanner (Siemens Healthcare, Germany) while completing the adolescent version of the ‘Reading the Mind in the Eyes’ Test. We conducted a whole brain analysis (controlling for sex and age) and examined the effect of genotype, diagnosis and the interaction between genotype and diagnosis on brain activation during the Eyes test. Analyses were conducted for each SNP separately. Results Examining brain activation when making a mental state decision, versus deciding the sex of the portrayed character (baseline condition), we found 3 SNPs with significant effects. For rs2254298 and rs53576 a region overlapping with the Inferior Parietal Lobule (IPL) showed hyperactivation during the mental state condition depending on genotype (F(1,60)=11.97, p value(FWE-corr)=0.010 and F(1,60)=11.97, p value(FWE-corr)=0.006, respectively) and on the interaction between genotype and diagnosis (F(1,60)=11.97, p value (FWE-corr)=0.009 and F(1,60)=11.97, p value (FWE-corr)=0.034, respectively). Increased activation in a region overlapping with the IPL was also found for rs2268491, but this was associated with the interaction only (F(1,60)=11.93, p value (FWE-corr)=0.009). For 2 (rs2228485, rs7632287) of the 5 SNPs, no cluster survived the family-wise correction (FWE) set at 0.05. Discussion The current study provides preliminary evidence that brain activation in response to a social task may be associated with both diagnostic status and common variation in the OXTR. Importantly, the IPL has been previously implicated in the affect sharing system. An imaging genetics approach might lend itself to increasingly accurate understanding of the heterogeneous autism phenotype.