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BRAIN DEVELOPMENT IN DEVELOPMENTAL DISORDERS

$429,037R01FY2000MHNIH

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

Autism is a severe neuropsychiatric disorder that affects young children with a disability that often continues throughout life. Because of the severe impairment and duration of this disorder, autism often confers a profound burden on autistic individuals, their families and society. Thus, research aimed at uncovering the pathogenesis of autism and potentially leading to rational approaches to prevention or treatment is of great importance. Our research team recently reported the presence of increased total brain volume (TBV) on MRI (including increased tissue and lateral ventricular volume) in autistic individuals. These findings are consistent with multiple reports of autistic individuals showing increased rates of macrocephaly (head circumference greater than or equal to 98th percentile) and post mortem studies showing increased brain weight and size. Head circumference studies by our group and others suggest that although enlarged head size may be present at birth, macrocephaly is not present until early childhood (age 4 years). Subsequent analyses of our MRI data suggest that cortical enlargement is the result of an increase in gray matter volume, further supporting our hypothesis that the increased rate of brain growth in autism occurs prior to age 5 years. Subsequent studies by our group and others have revealed a pattern of brain size and shape changes including: enlargement of the temporal, parietal and occipital (but not frontal) cortical lobes, that appears to be localized mostly to the right side of the brain; enlargement of the total cerebellar and caudate volume (proportionate to the increase in TBV); decreased size of some subregions of the corpus callosum; and, no change in size of the hippocampus. Clarification of the timing and pattern of brain growth and organization in autism will provide important insights into the pathogenesis and neural mechanisms underlying this disorder. Therefore we propose to conduct a longitudinal MRI study of the size and shape of the brain in autistic individuals and controls at 18-35 months of age with follow-up MRI brain scans of these same subjects after 24 months to examine the pattern of brain size and shape changes over time.

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