Longitudinal Magnetic Resonance Imaging Study of Cortical Development through Early Childhood in Autism

TLDR

Cross‑sectional MRI studies have long suggested that children with autism experience abnormal brain growth, including early overgrowth, but this has never been confirmed longitudinally. This study aimed to be the first longitudinal investigation of brain growth in toddlers when autism symptoms become clinically apparent, using structural MRI scans from 1.5 to 5 years of age. Researchers collected 193 structural MRI scans from 41 toddlers with confirmed autistic disorder (~48 months) and 44 typically developing controls across multiple time points between 1.5 and 5 years. By 2.5 years, toddlers with autistic disorder showed significant enlargement of cerebral gray and white matter, especially in frontal, temporal, and cingulate cortices, and longitudinal analysis revealed abnormal growth rates—quadratic with age—in all regions except occipital gray, with females displaying more pronounced abnormalities, indicating that overgrowth begins before age two and warrants earlier studies and biomarker characterization.

Abstract

Cross-sectional magnetic resonance imaging (MRI) studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however, this has never been confirmed by a longitudinal study. We performed the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent using structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of autistic disorder at ∼48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter were significantly enlarged in toddlers with autistic disorder, with the most severe enlargement occurring in frontal, temporal, and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with autistic disorder that was mainly characterized by a quadratic age effect. Females with autistic disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers to determine the underlying neuropathological processes causing the onset of autistic symptoms.