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Neurology 2003;60:100-107
© 2003 American Academy of Neurology

Regional brain chemical alterations in young children with autism spectrum disorder

S.D. Friedman, PhD, D.W. Shaw, MD, A.A. Artru, MD, T.L. Richards, PhD, J. Gardner, PhD, G. Dawson, PhD, S. Posse, PhD and S.R. Dager, MD

From the Departments of Radiology (Drs. Friedman, Shaw, Richards, Gardner, and Dager), Anesthesiology (Dr. Artru), Psychology (Dr. Dawson), Psychiatry (Dr. Dager), and Bioengineering (Drs. Richards and Dager), University of Washington School of Medicine, Seattle; and Wayne State University (Dr. Posse), Department of Psychiatry, Detroit, MI.

Address correspondence and reprint requests to Dr. Dager, Departments of Radiology, Psychiatry & Bioengineering, University of Washington School of Medicine, 4225 Roosevelt Way NE, Suite 306-C, Seattle, WA 98105-6099; e-mail: srd{at}u.washington.edu

Objective: The authors evaluated regional brain chemistry for evidence of increased neuronal packing density in autism.

Methods: Forty-five 3- to 4-year-old children with autism spectrum disorder (ASD), 13 children with typical development (TD), and 15 children with delayed development (DD) were studied using dual-echo proton echoplanar spectroscopic imaging (32 x 32 matrix-1 cm3 voxels) to measure brain chemical concentrations and relaxation times. Chemical quantification was corrected for tissue partial volume and relative measures of chemical relaxation (T2r) were calculated from the paired echoes. Measures from averaged and individual regions were compared using analysis of variance corrected for multiple comparisons.

Results: ASD subjects demonstrated reduced N-acetylaspartate (NAA) (-10%), creatine (Cre) (-8%), and myo-inositol (-13%) concentrations compared to TD controls and prolonged NAA T2r relative to TD (7%) and DD (9%) groups. Compared to DD subjects, children with ASD also demonstrated prolonged T2r for choline (10%) and Cre (9%). Regional analyses demonstrated subtle patterns of chemical alterations in ASD compared to the TD and DD groups.

Conclusions: Brain chemical abnormalities are present in ASD at 3 to 4 years of age. However, the direction and widespread distribution of these abnormalities do not support hypothesis of diffuse increased neuronal packing density in ASD.




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