Longitudinal Study of Amygdala Volume and Joint Attention in 2-to 4-Year-Old Children With Autism

Context: Cerebral cortical volume enlargement has been reported in 2- to 4-year-olds with autism. Little is known about the volume of subregions during this period of development. The amygdala is hypothesized to be abnormal in volume and related to core clinical features in autism. Objectives: To examine amygdala volume at 2 years with follow-up at 4 years of age in children with autism and to explore the relationship between amygdala volume and selected behavioral features of autism. Design: Longitudinal magnetic resonance imaging study. Setting: University medical setting. Participants: Fifty autistic and 33 control ( 11 developmentally delayed, 22 typically developing) children between 18 and 35 months ( 2 years) of age followed up at 42 to 59 months ( 4 years) of age. Main Outcome Measures: Amygdala volumes in relation to joint attention ability measured with a new observational coding system, the Social Orienting Continuum and Response Scale; group comparisons including total tissue volume, sex, IQ, and age as covariates. Results: Amygdala enlargement was observed in subjects with autism at both 2 and 4 years of age. Significant change over time in volume was observed, although the rate of change did not differ between groups. Amygdala volume was associated with joint attention ability at age 4 years in subjects with autism. Conclusions: The amygdala is enlarged in autism relative to controls by age 2 years but shows no relative increase in magnitude between 2 and 4 years of age. A significant association between amygdala volume and joint attention suggests that alterations to this structure may be linked to a core deficit of autism. Arch Gen Psychiatry. 2009;66(5):509-516