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Published Online: 1 June 2012

Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism

Jason J. Wolff, Ph.D., Hongbin Gu, Ph.D., Guido Gerig, Ph.D., Jed T. Elison, Ph.D., Martin Styner, Ph.D., Sylvain Gouttard, M.S., Kelly N. Botteron, M.D., Stephen R. Dager, M.D., Geraldine Dawson, Ph.D., Annette M. Estes, Ph.D., Alan C. Evans, Ph.D., Heather C. Hazlett, Ph.D., Penelope Kostopoulos, Ph.D., Robert C. McKinstry, M.D., Ph.D., Sarah J. Paterson, Ph.D., Robert T. Schultz, Ph.D., Lonnie Zwaigenbaum, M.D., and Joseph Piven, M.D. the IBIS NetworkAuthors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 169, Number 6
https://doi.org/10.1176/appi.ajp.2011.11091447
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Abstract

Children who developed autism spectrum disorders (ASDs) by age 2 had greater development of cerebral white matter fiber tracts by 6 months than unaffected children. After the initial accelerated white matter development, the children who developed ASDs had slower development, so that by age 2 their white matter development was less than that in the unaffected children.

Abstract

Objective:

Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months.

Method:

The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity.

Results:

The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values.

Conclusions:

These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 169 • Number 6 • June 2012
Pages: 589 - 600
PubMed: 22362397

History

Received: 28 September 2011
Revision received: 12 November 2011
Accepted: 5 December 2011
Published online: 1 June 2012
Published in print: June 2012

Authors

Affiliations

Jason J. Wolff, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Hongbin Gu, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Guido Gerig, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Jed T. Elison, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Martin Styner, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Sylvain Gouttard, M.S.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Kelly N. Botteron, M.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Stephen R. Dager, M.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Geraldine Dawson, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Annette M. Estes, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Alan C. Evans, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Heather C. Hazlett, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Penelope Kostopoulos, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Robert C. McKinstry, M.D., Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Sarah J. Paterson, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Robert T. Schultz, Ph.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Lonnie Zwaigenbaum, M.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Joseph Piven, M.D.
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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the IBIS Network
From the Carolina Institute for Developmental Disabilities and the Department of Psychiatry, University of North Carolina, Chapel Hill; the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City; the Department of Psychiatry and the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis; the Department of Radiology and the Department of Speech and Hearing Sciences, University of Washington, Seattle; Autism Speaks, New York; Montreal Neurological Institute, McGill University, Montreal; the Center for Autism Research, Children's Hospital of Philadelphia, and the University of Pennsylvania, Philadelphia; and the Department of Pediatrics, University of Alberta, Edmonton.
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Notes

Address correspondence to Dr. Wolff ([email protected]).

Funding Information

Dr. Evans reports having a 20% equity position in Biospective, Inc., an imaging contract research organization, as founder, and receiving a consulting fee from Biospective. All other authors report no financial relationships with commercial interests.Supported by grants from the National Institute of Child Health and Development (HD-055741, HD-055741-S1, HD-03110, HD-40127), Autism Speaks, and the Simons Foundation. Further support was provided by the National Alliance for Medical Image Computing, funded by the National Institute of Biomedical Imaging and Bioengineering through grant EB-005149.

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