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Brain. 2015 Jul;138(Pt 7):2046-58. doi: 10.1093/brain/awv118. Epub 2015 May 3.

Altered corpus callosum morphology associated with autism over the first 2 years of life.

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1 Department of Educational Psychology, University of Minnesota, Minneapolis, MN, USA
2 Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA.
3 Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
4 Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Boston, MA, USA 5 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
5 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 6 Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
7 Department of Psychiatry, Washington University at St. Louis, St. Louis, MO, USA.
8 Institute for Child Development, University of Minnesota, Minneapolis, MN, USA.
9 Department of Radiology, University of Washington, Seattle, WA, USA.
10 Department of Speech and Hearing Science, University of Washington, Seattle, WA, USA.
11 Centre for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
12 Department of Paediatrics, University of Alberta, Edmonton AB, Canada.


Numerous brain imaging studies indicate that the corpus callosum is smaller in older children and adults with autism spectrum disorder. However, there are no published studies examining the morphological development of this connective pathway in infants at-risk for the disorder. Magnetic resonance imaging data were collected from 270 infants at high familial risk for autism spectrum disorder and 108 low-risk controls at 6, 12 and 24 months of age, with 83% of infants contributing two or more data points. Fifty-seven children met criteria for ASD based on clinical-best estimate diagnosis at age 2 years. Corpora callosa were measured for area, length and thickness by automated segmentation. We found significantly increased corpus callosum area and thickness in children with autism spectrum disorder starting at 6 months of age. These differences were particularly robust in the anterior corpus callosum at the 6 and 12 month time points. Regression analysis indicated that radial diffusivity in this region, measured by diffusion tensor imaging, inversely predicted thickness. Measures of area and thickness in the first year of life were correlated with repetitive behaviours at age 2 years. In contrast to work from older children and adults, our findings suggest that the corpus callosum may be larger in infants who go on to develop autism spectrum disorder. This result was apparent with or without adjustment for total brain volume. Although we did not see a significant interaction between group and age, cross-sectional data indicated that area and thickness differences diminish by age 2 years. Regression data incorporating diffusion tensor imaging suggest that microstructural properties of callosal white matter, which includes myelination and axon composition, may explain group differences in morphology.


autism; brain development; corpus callosum; infants

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