Individual overall and tissue-specific brain development over time are, in general, known to be correlated with language, social, and emotional development. The severity of cognitive and behavioral functioning in autism spectrum disorders, therefore, may influence longitudinal brain development in affected individuals. At present, reliable quantification of such correlations is unavailable for autistic individuals. We thus investigated these relationships in a small sample of subjects with ASD.
The purpose of our study was to examine individual concurrent changes in the volumes of the total brain (TBV), total gray matter (TGM) and total white matter (TWM) and autism severity measures collected during the course of a five-year longitudinal study of high-functioning individuals with ASD. Our hypotheses were (1) a more rapid decrease of individual TBV, TGM and TWM volumes in autism vs. healthy development, and (2) the rapid volumetric decreases in autism would be associated with established measures of autism severity longitudinally.
Methods: Structural volumetric MR images were collected at 3T from 36 high-functioning individuals with ASD, each scanned between one and five times, with mean age 20.7 years (range 8.1 to 38.9 years) and mean inter-scan interval 3.1 years (range 0.25 to 10.2 years). TBV, TGM and TWM volumes were obtained from manually edited FreeSurfer segmentations. These volumetric time series were then inspected by longitudinal analysis of covariance that accounted for age, age at first scan, and change in ADI-R score, with multiple scans per subject as the repeated measure.
Results: For those subjects that improved clinically (better ADI-R score), TBV with initial mean 1380.4 (range 1006.2, 1632.5) decreased by 19.9 cm3/year (p < 0.000005). TGM for this group, with initial mean 824.9 (range 569.2, 958.8), decreased by 13.4 cm3/year (p < 0.000005). TWM for this group, with initial mean 517.3 (range 379.9, 730.5), decreased by 6.1 cm3/year (p < 0.000005). For those that worsened or had no change clinically (poorer or no change in ADI-R score), TBV with initial mean 14.89.9 (range 1151.5, 1606.2) decreased by 17.0 cm3/year (p = 0.00002). TGM for this group, with initial mean 888.2 (range 670.1, 953.1), decreased by 14.2 cm3/year (p < 0.000005). TWM for this group, with initial mean 564.9 (range 403.2, 659.6), decreased by 3.4 cm3/year (p > 0.35, n.s.).
Conclusions: In our sample of high-functioning individuals with autism, we have identified precipitous drops in the volumes of the total brain, total gray matter, and total white matter that are greater than the mean decreases (TBV, TGM) and increases (TWM) seen in healthy development by a factor of four. These extreme changes appear to occur between late childhood and early-mid adulthood. Rapid decreases in brain size are not associated with clinical improvement, and, in many cases, autism severity appears to worsen over time for those with larger initial brain volumes, while accounting for the effect of age at first scan. These drops were more pronounced in total gray matter volume, with no significant change in white matter volume in the group that did not improve clinically.
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