Abstracts

Rationale: Comorbidity of epilepsy and autism spectrum disorder (ASD) is well established, suggesting shared neurobiological and genetic mechanisms. However, the extent to which shared mechanisms are causal to the comorbidity remains undetermined. The high rate of intellectual disability in individuals with comorbid epilepsy and ASD poses a significant challenge to elucidating this.The Broader Autism Phenotype (BAP) refers to mild autism traits relating to social and communication difficulties and restricted and repetitive behaviors and interests. The BAP is observed in 20% of first-degree relatives of individuals with ASD, and may be a marker of autism susceptibility genes. Our first aim was to compare the rate of the BAP in people with seizures (PWS) without intellectual disability, to the general population and relatives of individuals with ASD (ASD-relatives). Our second aim was to examine the BAP trait profile of PWS compared to individuals without the BAP recruited from the local community. Methods: First, we used the Broad Autism Phenotype Questionnaire (BAPQ) to assess the BAP in 103 consecutively recruited PWS (Mage =37.4 years, SD =12.5; MIQ = 104.0, SD =12.4; 48 males) and compared the rate of the BAP in these individuals to published rates in the general population and to those in ASD-relatives, retrieved through a systematic literature search (cohorts  >100 individuals).Second, we combined the BAPQ and Autism Endophenotype Interview (AEI), a semi-structured interview and observational measure, to determine the rate of the BAP in PWS and 58 individuals recruited from the local community (Mage =39.6 years, SD =14.6; MIQ =113.0, SD =11.6; 20 males). Third, individuals without the BAP in the local community sample (n=35) were used as controls for characterization of the BAP profile in PWS. Results: PWS had a higher rate of the BAP (21%) compared to the general population (6%; p 0.05). Cluster analysis of combined BAPQ and AEI scores found that 40% of PWS had the BAP. Epilepsy-related variables (e.g. age at seizure onset, time since onset, seizure frequency) were not associated with BAP status (p >0.05). Compared to controls, PWS and the BAP had higher scores across the social, pragmatic language, and restricted and repetitive behaviors and interests domains of the BAP. Conclusions: Our findings show that the rate of PWS with the BAP varies from 21% to 40%, depending on the measures used. Our findings suggest that a more detailed profile analysis doubles the identification of individuals with the BAP. These data suggest overlap in the etiological mechanisms of epilepsy and ASD and raise the possibility that previous delineation of the “epileptic personality” may in fact represent people with the comorbidity of the BAP in PWS. This has important implications for the clinical management of PWS. Funding: The study was supported by the National Health and Medical Research Council of Australia Project grant and an Australian Postgraduate Award.