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Published June 2014 | Supplemental Material + Accepted Version
Journal Article Open

Agenesis of the corpus callosum and autism: a comprehensive comparison


The corpus callosum, with its ∼200 million axons, remains enigmatic in its contribution to cognition and behaviour. Agenesis of the corpus callosum is a congenital condition in which the corpus callosum fails to develop; such individuals exhibit localized deficits in non-literal language comprehension, humour, theory of mind and social reasoning. These findings together with parent reports suggest that behavioural and cognitive impairments in subjects with callosal agenesis may overlap with the profile of autism spectrum disorders, particularly with respect to impairments in social interaction and communication. To provide a comprehensive test of this hypothesis, we directly compared a group of 26 adults with callosal agenesis to a group of 28 adults with a diagnosis of autism spectrum disorder but no neurological abnormality. All participants had full-scale intelligence quotient scores >78 and groups were matched on age, handedness, and gender ratio. Using the Autism Diagnostic Observation Schedule together with current clinical presentation to assess autistic symptomatology, we found that 8/26 (about a third) of agenesis subjects presented with autism. However, more formal diagnosis additionally involving recollective parent-report measures regarding childhood behaviour showed that only 3/22 met complete formal criteria for an autism spectrum disorder (parent reports were unavailable for four subjects). We found no relationship between intelligence quotient and autism symptomatology in callosal agenesis, nor evidence that the presence of any residual corpus callosum differentiated those who exhibited current autism spectrum symptoms from those who did not. Relative to the autism spectrum comparison group, parent ratings of childhood behaviour indicated children with agenesis were less likely to meet diagnostic criteria for autism, even for those who met autism spectrum criteria as adults, and even though there was no group difference in parent report of current behaviours. The findings suggest two broad conclusions. First, they support the hypothesis that congenital disruption of the corpus callosum constitutes a major risk factor for developing autism. Second, they quantify specific features that distinguish autistic behaviour associated with callosal agenesis from autism more generally. Taken together, these two findings also leverage specific questions for future investigation: what are the distal causes (genetic and environmental) determining both callosal agenesis and its autistic features, and what are the proximal mechanisms by which absence of the callosum might generate autistic symptomatology?

Additional Information

© 2014 The Author. Published by Oxford University Press on behalf of the Guarantors of Brain. Received September 13, 2013. Revised December 12, 2013. Accepted January 13, 2014. First published online: April 25, 2014. The authors wish to thank Catherine Holcomb for help in recruiting and testing subjects, Mike Tyszka for help with neuroimaging analyses, and Deborah Childress for help with ADOS administration. Funding: This work is supported in part by grants from the National Institutes of Mental Health (R01MH080721) and the Simons Foundation Autism Research Initiative to R.A., a National Alliance for Research on Schizophrenia and Depression Young Investigator Award presented to L.K.P, and a grant from the National Institutes of Mental Health (K99/R00MH094409) and a Brain and Behavior Research Foundation Young Investigator Award to D.P.K.

Attached Files

Accepted Version - BRAIN-2013-01637.R1.pdf

Supplemental Material - suppl_data.zip


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