International Meeting for Autism Research: Growth Curves for Longitudinal Regional Brain Volumes in Autism Vs. Typical Development

Growth Curves for Longitudinal Regional Brain Volumes in Autism Vs. Typical Development

Saturday, May 22, 2010: 9:45 AM
Grand Ballroom E Level 5 (Philadelphia Marriott Downtown)
9:45 AM
J. E. Lainhart , Psychiatry, University of Utah, Salt Lake City, UT
C. Ravichandran , Laboratory for Psychiatric Biostatistics, McLean Hospital/Harvard Medical School, Belmont, MA
A. Froehlich , Psychiatry, University of Utah, Salt Lake City, UT
M. B. DuBray , Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT
T. Abildskov , Brigham Young University
E. Bigler , Neuropsychology, University of Utah, Salt Lake City, UT
A. L. Alexander , Department of Medical Physics, Department of Psychiatry, Waisman Laboratory for Brain Imaging & Behavior, University of Wisconsin, Madison, WI
N. Lange , Departments of Psychiatry and Biostatistics, Harvard University, Belmont, MA
Background: Although cross-sectional samples of regional brain volumes in autism are widely available, longitudinal samples are few and of smaller sample size covering shorter age spans. The necessary caveats on reported associations between age and brain structure sizes in autism derived from these samples remain. Clinically useful growth curves for regional volumetric brain development in autism are severely lacking and highly needed.

Objectives: Our goal is to derive valid and reliable volumetric growth curves for total and regional brain development in autism and to compare them to corresponding growth curves in typical development.

Methods: The subset of our larger longitudinal sample studied thus far contained N = 102 high-functioning males on the autism spectrum aged 3-40 years, matched with N = 53 typically-developing controls. We extracted volumes of all oft-used brain structures by FreeSurfer. The number of scans/subject was 1 (20 autism, 17 control), 2 (55 autism, 27 control) and 3 (26 autism, 26, 11 control). We conducted a longitudinal growth-curve analysis of each structural volume separately to determine its possible dependence on group, age, and group by age interaction.

Results: (1) In autism, while controlling for volume-age associations, we found that all regional volumes depended on total brain size, except for ventricular volume. Relationships between total and regional brain volumes were similar in autism and controls except in the putamen and mid-posterior corpus callosum (CC); volumes of these regions were found to depend more strongly on total brain size in autism (both p < 0.00005). (2) No group mean volume differences were observed for any structure when we accounted for age and total brain size associations. (3) All volumetric growth-curves in both groups were found to be linear in age; no quadratic or other curvilinear relationships were detected. The following regions showed significant volumetric changes with age in autism but not in typical development: intracranial cavity (increasing), cerebrum (decreasing), gray matter (decreasing), white matter (increasing) (all p<0.00005) and ventricles (increasing) (p=0.0391). The total and regional mean volumes and coefficients of variation of our control sample were consistent with those observed in the recent large nationwide study of representative healthy brain development (N = 152 males). Linear volumetric changes with age found in the subset of our control sample 4.8-18.3 years of age matching the age range of the nationwide sample.

Conclusions: As indicated by our wide 3-40 year age range, volumetric growth-curves suggest that total and regional brain growth may be more protracted in autism than in typical development. Total and regional brain structure sizes in autism appear, thus far, to conform to typical values with the 4.8–18.3 range derived from the nationwide longitudinal study of typical peers. More detailed and comprehensive studies of our longitudinal sample are underway, specifically of a possible disturbance in associations between total brain and putamen and mid-posterior CC sizes Acknowledgements and Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of Mental Health or the National Institutes of Health.

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