Although a variety of data strongly indicate that autism is a neurodevelopmental disorder, the etiology of this disorder remains unknown. Neuroimaging methods offer the unique capability of studying neural abnormalities in vivo. However, due in part to heterogeneity of diagnostic methods, study design and image measurement procedures, there are few replicated findings in the neuroimaging literature of autism. This project seeks to rectify these problems by combining the efforts of two research laboratories active in the investigation of the neurobiology of autism (UCLA and Yale), expanding their resources and sample sizes, and employing a uniform set of core diagnostic, neuropsychological and imaging methodologies across centers to address several critical hypotheses regarding the pathophysiology of autism. All high functioning probands and unaffected controls in the Project Family Genetics, will undergo the neuroimaging protocol at the UCLA or Yale site, and will be assessed with identical diagnostic and neuropsychological procedures. Structural neuroimaging data will be combined for statistically powerful examination of potentially subtle neuroantomic differences between autistic subjects and controls including: volume of the amygdala, hippocampus and select frontal lobe regions, total brain volume, neurodevelopmental abnormalities, and cross-sectional areas of the corpus callosum and the cerebellar vermis. MRI data from the subjects with autism will be compiled into a computerized atlas and compared to a similar atlas of normal development. Yale will further its effort to validate the distinction between higher functioning autism and Asperger syndrome, and extend pilot work using functional MRI to study the perception of faces and emotional expressions. This project would represent the first study to integrate genetics, in vivo imaging and behavioral research methodologies in a large sample of autistic subjects and well matched controls, thus providing a unique opportunity to better understand the varying manifestations of autism.
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