Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms emerging during
early childhood. The pathophysiology underlying the disorder remains incompletely understood.
To examine cross-sectional and longitudinal patterns of brain chemical concentrations in children
with ASD or idiopathic developmental delay (DD) from 3 different age points, beginning early in the
Proton magnetic resonance spectroscopic imaging data were acquired longitudinally for children
with ASD or DD, and primarily cross-sectionally for children with typical development (TD), at 3 to
4, 6 to 7, and 9 to 10 years of age.
Recruitment, diagnostic assessments, and magnetic resonance imaging were performed at the
University of Washington in Seattle.
Seventy-three children (45 with ASD, 14 with DD, and 14 with TD) at 3 to 4 years of age; 69
children (35 with ASD, 14 with DD, and 20 with TD) at 6 to 7 years of age; and 77 children (29 with
ASD, 15 with DD, and 33 with TD) at 9 to 10 years of age.
Main Outcomes and Measures
Concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr),
myo-inositol (mI), and glutamine plus glutamate (Glx) in cerebral gray matter (GM) and white matter
(WM) at 3 to 4, 6 to 7, and 9 to 10 years of age, and calculation of rates of change of these
chemicals between 3 and 10 years of age.
At 3 to 4 years of age, the ASD group exhibited lower NAA, Cho, and Cr concentrations than did
the TD group in both GM and WM, alterations that largely were not observed at 9 to 10 years of age.
The DD group exhibited reduced GM and WM NAA concentrations at 3 to 4 years of age; GM NAA
concentrations remained reduced at 9 to 10 years of age compared with the TD group. There were
distinct differences between the ASD and DD groups in the rates of GM NAA, Cho, and Cr changes
between 3 and 10 years of age.
Conclusions and Relevance
The GM chemical changes between 3 and 10 years of age differentiated the children with ASD from
those with DD. Most notably, a dynamic reversal of GM NAA reductions was observed in the children
with ASD. By contrast, persistent GM NAA reductions in the children with DD suggest a different,
more static, underlying developmental process.