Agenesis of the corpus callosum and autism: a comprehensive comparison

Abstract

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?

A Neuropsychological Profile for Agenesis of the Corpus Callosum? Cognitive, Academic, Executive, Social, and Behavioral Functioning in School-Age Children

“…Significant behavioral and social difficulties were observed in our cohort, consistent with previous studies. Furthermore, a high rate of ASD symptoms was observed, with more than half of parents and teachers reporting clinical levels of ASD in our cohort (Paul et al, 2014;Paul et al, 2004). Consistent with previous AgCC studies that have reported a higher proportion of left-handers than in the general population, ranging from 24% to 56% (e.g., Lábadi & Beke, 2017;Sauerwein & Lassonde, 1994;Chiarello, 1980), in our AgCC cohort almost half of the children were left-handed.…”

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

“…The genetics of corpus callosum biology is, however, highly heterogeneous, and despite technological advances in next generation sequencing, 75% of callosal disorders have no identified genetic cause (11). Recent studies have suggested that a smaller corpus callosum is associated with a higher risk for autisms (12), bipolar disorder (13), and schizophrenia (14). Corpus callosum abnormalities are often seen in conjunction with other defects, such as smaller or larger brain size and malformations of cortical development (15).…”

Corpus callosum in cognitive and sensory processing: insights into autism

“…The pattern of deficits was generally in the social skills, imagination, communication and mind reading domains; however, no differences were reported in the attention to detail domain, which has questions pertaining to noticing small sounds, vision information (e.g., license plate REviEW Demopoulos, Yu, Paul, Sherr & Marco future science group numbers) and patterns. Paul et al [58] conducted comprehensive autism diagnostic assessments in 26 adolescents and adults with AgCC using gold standard autism diagnostic tools, the ADI-R [59] and ADOS [60]. Unlike the previous studies, this sample included only individuals with AgCC who also had a Full Scale Intelligence Quotient greater than 78, no known chromosomal anomaly or genetic syndromes and minimal additional neuropathology on MRI (i.e., participants were not excluded for structural abnormalities which commonly co-occur with AgCC, including colpocephaly, Probst bundles, interhemispheric cysts and small heterotopias).…”

“…These studies leave open the question as to whether autistic behaviors in AgCC are more prevalent in children or adults [56]. Behavioral data suggest that in higher functioning individuals with AgCC unlike idiopathic autism, autistic behaviors may emerge during later childhood and adolescence [58]. Moreover, among the 70% of participants whose current behavior did not meet full criteria for autism, half of the tested individuals did exhibit deficits of social and/or communication skills.…”