Autism spectrum disorder (ASD), characterized by core challenges in socialization and restrictive and repetitive behaviors, has a complicated relationship with intellectual disability (ID), which is characterized by core difficulties in cognitive skills (verbal reasoning, information processing, etc.). Although ASD and ID are two distinct neurodevelopmental conditions, they are highly comorbid, and the socialization features associated with ASD and the cognitive features associated with ID are confounded. Because of this pervasive confound of ID in ASD, parsing the causal biological factors related specifically to autism presents challenges, even in the face of ongoing, large-scale genomic and brain imaging studies. Currently, there is no large-scale cohort of ASD that is expressly free of ID, and this represents a significant barrier for the field.

To eliminate the confounding effects of very low cognitive ability, Jacob Michaelson and colleagues will recruit a highly unique cohort of extremely high-ability individuals with ASD and will collect genetic, brain imaging and extensive psychoeducational data from these individuals. In the psycho-educational literature, individuals with high cognitive ability and a co-occurring disability or condition, such as ASD, are referred to as twice exceptional (2e). Because high cognitive ability is in direct contrast to ID, an investigation of 2e individuals with ASD may provide a window into the molecular and neuroanatomical aspects of ASD that distinguish it from ID.

The foundation of the study will be the digitization of ~1,800 psychoeducational records from the Belin-Blank Center at the University of Iowa, which has a specialized clinical operation serving 2e individuals. Using recruitment materials designed specifically for this population, 2e individuals will be recruited from this database and enrolled in SPARK (Simons Foundation Powering Autism Research for Knowledge), while high-ability typically developing individuals will be enrolled in a local registry and have salivary DNA collected and stored for use in follow-up studies as ability-matched controls for 2e participants. A pilot magnetic resonance imaging (MRI) study will be performed to pave the way for scaled-up studies of brain anatomy and connectivity as it relates to twice exceptionality.

Such a cohort has not been previously assembled at this scale, and the success of this project will have a significant impact on ASD research. The cohort will enable examination of the biological processes that are unique to ASD (i.e., without the confound of intellectual disability), thus informing potential therapeutic mechanisms for the core symptoms of ASD. It will permit investigation into whether ASD and high ability in these 2e individuals arise from distinct co-occurring processes, or processes that simultaneously confer abilities in some domains and liabilities in others. Finally, this work will provide insights into an underserved population that has a latent potential for great societal contribution if more can be done to help them reach their potential, particularly with regard to severe challenges in social communication and comorbid learning disabilities.