Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders.

Autism is a heterogeneous disorder with multiple behavioral and biological phenotypes. Accelerated brain growth during early childhood is a well-established biological feature of autism. Onset pattern, i.e., early onset or regressive, is an intensely studied behavioral phenotype of autism. There is currently little known, however, about whether, or how, onset status maps onto the abnormal brain growth. We examined the relationship between total brain volume and onset status in a large sample of 2- to 4-y-old boys and girls with autism spectrum disorder (ASD) [n = 53, no regression (nREG); n = 61, regression (REG)] and a comparison group of age-matched typically developing controls (n = 66). We also examined retrospective head circumference measurements from birth through 18 mo of age. We found that abnormal brain enlargement was most commonly found in boys with regressive autism. Brain size in boys without regression did not differ from controls. Retrospective head circumference measurements indicate that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4-6 mo of age. There were no differences in brain size in girls with autism (n = 22, ASD; n = 24, controls). These results suggest that there may be distinct neural phenotypes associated with different onsets of autism. For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported. Thus, rapid head growth may be a risk factor for regressive autism.

Brief report: symptom onset patterns and functional outcomes in young children with autism spectrum disorders.

This study examined the relationship between onset status and current functioning using a recently proposed onset classification system in 272 young children with autism spectrum disorder (ASD). Participants were classified into one of the following groups, based on parent report using the Autism Diagnostic Interview--Revised: Early Onset (symptoms by 12 months, no loss), Delay + Regression (symptoms by 12 months plus loss), Plateau (no early symptoms or loss), and Regression (no early symptoms, followed by loss). Findings indicate that current functioning does not differ according to onset pattern, calling into question the use of onset categorizations for prognostic purposes in children with ASD.