Psychosocial Phenotype of Agenesis of the Corpus Callosum

Background:   Parent reports suggest that behavioral symptoms in children with AgCC overlap with the autism spectrum disorders (ASD), particularly with respect to impairments in social interaction and communication (Badaruddin et al., 2007). In fact, autism screening instruments suggest that up to 45% of children with AgCC have significant symptoms on the autism spectrum. 

Objectives:   To clarify the phenotypic overlap of AgCC and ASD as assessed with both standardized diagnostic measures and experimental measures targeting specific aspects of the ASD diagnosis.

Methods: The first half of the presentation draws from multiple studies of psychosocial processing involving over 70 children and adults with isolated AgCC. These studies examined comprehension of affective prosody, theory of mind, social attribution, affect naming from faces, and affective responses to stimuli. The second section of the presentation focuses on a comprehensive diagnostic assessment in 27 adolescents and adults (ages 16 – 54) with isolated AgCC. We will report data from the Autism Diagnostic Observation Schedule (ADOS), either Autism Diagnostic Inventory – Revised (ADI-R) or Social Communication Questionnaire (SCQ), and a clinical diagnosis. Finally, we will present new fMRI data examining lateralization of language processes in individuals with complete AgCC.

Results: Individuals with AgCC exhibit deficits in non-literal language comprehension (e.g., Paul, Van Lancker-Sidtis, Schieffer, Dietrich, & Brown, 2003), theory of mind (e.g., Symington, Paul, Symington, Ono & Brown, 2010), and social reasoning (e.g., Turk, Brown, Symington, & Paul, 2010). Results from several additional recent (as yet unpublished) studies have found clear similarities to the findings in high functioning adults who have autism. For example, adults with AgCC have significant difficulty attributing mental states to non-human animations, although they can identify goal-directed behavior. Additionally, emotion naming from facial expressions and eye-tracking patterns when looking at faces are also similarly impaired in AgCC and ASD. Both groups were particularly impaired in identifying fearful faces and attended significantly less to the eyes than their peers.

Regarding ASD diagnosis, stringent application of observation, parent report and clinical assessment methods identified that one-third of adults with AgCC (9 out of 27) meet criteria for an ASD on all three measures. Of the 18 who did not meet full criteria, 7 met ASD criteria on a parent report that emphasizes functioning between ages 4 and 5. This suggests that in early childhood, the rate of ASD diagnosis may be over 50% in the AgCC population.

Finally, in a select sample of 8 right-handed adults with complete isolated AgCC, we identified typical cortical lateralization for motor production, but decreased laterality of language generation.

Conclusions: The behavioral phenotype of AgCC overlaps substantially with ASD and these similarities may be even more evident in childhood. Impaired non-literal language comprehension, facial processing, mental state attribution and social reasoning appear to play a significant role in the social phenotype of AgCC, suggesting that connectivity may be particularly relevant for these skills in ASD as well.