Caudate Volume In Preschool Age Children with Autism

Background: Previous investigations into the neuropathology of autism have suggested that the caudate nucleus is enlarged in older children and adolescents with autism. Moreover, associations between caudate volume and repetitive behavior have also been reported. However, few studies have examined the caudate in very young children with autism.

Objectives: To evaluate whether abnormal enlargement of the caudate nucleus is present in very young children with autism spectrum disorders (ASD) relative to age-matched typically developing (TD) controls. We also investigated the relationship between repetitive behavior and caudate volume.

Methods: High-resolution structural MRIs were acquired during natural nocturnal sleep. Caudate volume was measured in 88 participants (58 ASD, 30 TD) between 2.1 - 4.6 years of age. Autism diagnoses were conducted by trained, experienced psychologists using the ADOS and ADI-R.  Severity of repetitive behavior deficits was measured using the Repetitive Behavior Scale (RBS), a parent-report questionnaire. Two researchers, blinded with respect to diagnosis, manually traced the right and left caudate using Analyze 10.0 software after achieving an inter-rater reliability of .94 ICC.

Results: There was no significant overall group difference in the caudate volume between children with autism and age-matched TD controls. Preliminary analyses within the autism group show there was a significant difference in right and left caudate volume between children who had early onset autism compared to those with regression (p=0.03). Right and left caudate volumes were 7% smaller in children with early onset autism (n = 28) compared to those with regression (n = 27). Children with early onset autism also had more severe RBS scores compared to children with regression (p=0.03). This is consistent with a trend suggesting that smaller caudate volume is related to more severe repetitive behavior in all children with ASD (r = -.23, p = .13). 

Conclusions: Abnormal caudate enlargement is not present in very young children with autism. However, autism is an extremely heterogeneous disorder, and preliminary data suggest that caudate volume may be associated with onset status of autism. Interestingly, these data suggest that smaller caudate volumes were associated with more severe repetitive behavior symptoms in very young children. Additional studies with larger sample sizes and longitudinal analyses will be necessary to understand the role of the caudate in the neuropathology of autism.