Multiple lines of converging evidence document brain enlargement in autism. Magnetic resonance imaging (MRI) studies have revealed generalized enlargement in the cerebral cortex and some subcortical structures by the age of 2 years. Studies of head circumference among high-risk infants suggest that brain overgrowth begins at 6-12 months, and behavioral studies of infants suggest that the defining features of autism generally appear by 12 months of age.

Joseph Piven and collaborators aim to identify early behavioral and neurobiological features that characterize infants who later develop an autism spectrum disorder. Their study is currently enrolling 500 infant siblings of older children with autism, whose brains will be examined with magnetic resonance and diffusion tensor imaging. In addition, the team plans to carry out detailed behavioral assessments and genome-wide analysis at 6, 12 and 24 months of age. Infants at high risk for autism will be compared with a group of 150 typically developing infants and an additional sample of 30 infants carrying the fragile X mutation.

Through this longitudinal (from 6 to 24 months) study of high-risk siblings, Piven and colleagues expect to be able to identify behavioral, familial and neurobiological features that characterize infants who develop autism across a range of symptom severity.

The investigators predict that infants who go on to develop an autism spectrum disorder will begin to show marked changes in behavior around 12 months of age in association with increases in brain volume and changes in the maturation of selected fiber tracts in brain areas thought to be most central to the problems in young children with autism. The availability of genotypic information will enable this research team to examine longitudinal trajectories of brain and behavioral development in relationship to specific genes of interest in autism.