Saturday, May 22, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
11:00 AM
Background: Impairments in social functioning are the defining, core feature of autism spectrum disorders (ASD). Although it is accepted that ASD are neurodevelopmental disorders, no widely applicable genetic or neurochemical markers with diagnostic or prognostic utility have been identified. Researchers have theorized, however, that the neurobiological systems critical for social functioning in healthy individuals are promising candidates for investigation in autism. One such candidate is oxytocin (OT), and several lines of evidence support its potential role in ASD. OT and its receptor (OTR) are critically involved in social behavior and social cognition, whereas OT and OTR impairments induced pharmacologically or through genetic manipulation produce diverse social deficits in animals. Importantly, preliminary research in multiple patient populations suggests that certain OTR single nucleotide polymorphisms (SNPs) increase risk for autism, and that plasma OT levels are lower in autistic compared to typically developing control children.
Objectives: We hypothesize that the degree of impairment in social functioning is associated with genetic OTR polymorphisms (e.g., rs53576) previously associated with autism. As part of our larger research program, we also hypothesize that variability in plasma OT concentrations is associated with differences in social functioning. Methods: Participants included children with autism and typically developing control children. An extensive behavioral phenotype battery was completed on all subjects, and included the Social Responsiveness Scale (SRS). Autism diagnosis was based on the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview Revised, and expert clinical opinion. Blood samples were collected from all subjects for DNA extraction and genotyping of OTR SNPs using standard SNP genotyping methods. Plasma aliquots were frozen for subsequent quantification of OT concentrations, and data will be presented if available.
Results: To date 90 participants have enrolled and completed the study procedures, including 43 children with ASD and 47 control children. We have analyzed SNP genotypes from the OTR for these subjects. In our initial analysis we did not detect any difference in overall social functioning for any of the OTR SNPs under investigation. However, our preliminary data indicate that the homozygous AA genotype of the OTR rs53576 is associated with increases in some social deficits as measured by the SRS in comparison to either the AG or GG genotypes. In contrast, in the control population this AA genotype is not associated with increased social deficits.
Conclusions: These preliminary data suggest that in autistic individuals carrying the AA genotype of rs53576 may increase vulnerability to social impairments. These findings are in agreement with prior studies examining this SNP in measures of social functioning and suggest that variability in the OTR may modulate social behavior in autism. While our preliminary findings need to be replicated in a larger cohort, it is possible that a better understanding of OT biology may lead to improved prognostic and possibly therapeutic approaches in autism.
Objectives: We hypothesize that the degree of impairment in social functioning is associated with genetic OTR polymorphisms (e.g., rs53576) previously associated with autism. As part of our larger research program, we also hypothesize that variability in plasma OT concentrations is associated with differences in social functioning. Methods: Participants included children with autism and typically developing control children. An extensive behavioral phenotype battery was completed on all subjects, and included the Social Responsiveness Scale (SRS). Autism diagnosis was based on the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview Revised, and expert clinical opinion. Blood samples were collected from all subjects for DNA extraction and genotyping of OTR SNPs using standard SNP genotyping methods. Plasma aliquots were frozen for subsequent quantification of OT concentrations, and data will be presented if available.
Results: To date 90 participants have enrolled and completed the study procedures, including 43 children with ASD and 47 control children. We have analyzed SNP genotypes from the OTR for these subjects. In our initial analysis we did not detect any difference in overall social functioning for any of the OTR SNPs under investigation. However, our preliminary data indicate that the homozygous AA genotype of the OTR rs53576 is associated with increases in some social deficits as measured by the SRS in comparison to either the AG or GG genotypes. In contrast, in the control population this AA genotype is not associated with increased social deficits.
Conclusions: These preliminary data suggest that in autistic individuals carrying the AA genotype of rs53576 may increase vulnerability to social impairments. These findings are in agreement with prior studies examining this SNP in measures of social functioning and suggest that variability in the OTR may modulate social behavior in autism. While our preliminary findings need to be replicated in a larger cohort, it is possible that a better understanding of OT biology may lead to improved prognostic and possibly therapeutic approaches in autism.