Gray and white matter brain chemistry in young children with autism

Context: The brain pathophysiological abnormalities underlying autism remain unclear. Neuroimaging and histological studies suggest cellular abnormalities early in the course of the disease. Objective: To measure the in vivo chemical profile of gray and white matter tissues in autism. Design: Cross-sectional spectroscopic imaging study comparing 3- to 4-year-old children with autism spectrum disorder (ASD) with age-matched comparison groups of children with delayed development (DD) and typical development (TD). Setting: The University of Washington Diagnostic Imaging Sciences Center, Seattle. Participants: Forty-five 3- to 4-year-old children with ASD, 12 age-matched children with DD, and 10 age-matched children with TD. Main Outcome Measures: Estimates of gray and white matter concentrations for choline-containing compounds (Cho), creatine plus phosphocreatine, N-acetylaspartate (NAA), and myo-inositol (mI). Transverse relaxation times for Cho, creatine plus phosphocreatine, and NAA expressed relative to control subjects with TD were examined to evaluate tissue compactness. Results: The children with ASD demonstrated decreased gray matter concentrations of Cho (P <.001), creatine plus phosphocreatine (P=.02), NAA (P=.02), and mI (P=.008) compared with children with TD. Gray matter Cho transverse relaxation was also prolonged for the ASD sample compared with the TD group (P=. 01). The children with ASD demonstrated significantly decreased levels of Cho (P=. 04) and mI (P=. 008) and trend-level NAA (P=. 09) in gray matter compared with the DD group. For white matter, both children with ASD and children with DD showed a similar pattern of NAA and mI level decreases (for children with ASD vs children with TD: NAA, P=. 03; mI, P=. 04; for children with DD vs children with TD, NAA, P=. 03; mI, P=. 07). In several analyses, cerebral volume contributed significantly as a covariate. Conclusions: Reduced gray matter chemical concentrations and altered Cho transverse relaxation, in a pattern distinct from that in children with DD, suggest decreased cellularity, or density, at this early time point in ASD. Possibly reflecting shared developmental features, white matter results were common to ASD and DD groups. The relationship between cerebral volume and neurochemistry at this early time point may indicate processes related to unit scaling.