Total Cerebral Volume Is Associated with Onset Status In Preschool Age Children with Autism

Background: Autism is a heterogeneous disorder, and multiple behavioral and biological phenotypes likely exist. One well-characterized behavioral phenotype is onset status. While some children with autism exhibit symptoms very early in life, others experience a regression or loss of previously acquired skills. There is currently very little known about the neural substrates associated with these two different behavioral trajectories in autism.

Objectives: We examined the relationship between total brain volume and onset status in a large sample of 2-4 year old children with autism spectrum disorder (ASD) (n = 48, early onset, n = 58, regression) and a comparison group of age-matched typically developing children (TD) (n = 55).

Methods: Diagnoses and autism severity were based on ADOS and ADI-R scores and clinical judgment by trained, experienced psychologists. Developmental quotients (DQ), verbal quotients (VQ) and nonverbal quotients (NVQ) were based on the Mullen Scales.  Onset status was categorized based on parent reports from related ADI-R questions. Total cerebral volume was compared between autism onset groups as well as relative to age-matched typically developing controls. Autism severity and DQ were also evaluated in relation to brain volume and onset status.

Results: Children who exhibited regression had significantly larger total brain volumes than children with early onset autism (p = .004). Total brain volume in the early onset ASD group did not differ from the TD group, whereas total brain volume was significantly larger in the children with regression. Moreover, children with regression had significantly lower VQ (p = .03) and higher (i.e. more severe) ADOS social and communication scores (p = .02).  Total brain enlargement remained significant even after controlling for these variables. There were no significant correlations between total brain volume and VQ or ADOS scores.

Conclusions: Total brain enlargement has been reported in children with autism under the age of five. However, behavioral associations with abnormal brain enlargement have not been fully explored. Our findings suggest that abnormal brain enlargement in autism is associated with a parent-reported regressive pattern of onset and more severe symptoms involving both developmental impairment and ASD severity.