Essential to understanding the symptomatology of autism is the need to unravel its neurophysiology, neurochemistry, and neuropathology. Progress in understanding its pathophysiology has been stymied by a dearth of post-mortem tissue. This Program Project focuses on sensorimotor deficits, their pharmacologic treatment, and their neural basis. The Core will provide a group of well-characterized DSM IV autistic children and a common data base for statistical analysis. In Project l, we will investigate the physiologic basis of aberrant auditory processing by systematically assessing cochlear, brainstem, and cortical auditory function (automatic and attentional discrimination of auditory stimuli). Abnormalities in timing, amplitude and topographic patterns of cortical event related potentials will be identified. In Project II, we will test the hypothesis that excessive endogenous brain opiods contribute to autistic behaviors by assessing the effectiveness of naltrexone, an opioid antagonist, in conventional and ultra-low doses on sociability, hyperactivity, attention, stereotypies, and self- injurious behavior. In animal studies we will localize changes in neural activity associated with naltrexone treatment. Project III will create an international registry of autistic brain specimens and a brain bank to provide the essential material for the scientific community's and our own studies of morphology, opioid and other neurotransmitters and receptors, growth factors, and apoptosis. We will canvas new neuropathologists nationally, and proselytize parent support groups and chronic disease facilities with the pressing need for brain donations. The applicants bring to this project many years of scientific collaboration and experience in brain banking, and management and participation in multidisiplinary research on autism and other cognitive disorders under the aegis of the Rose F. Kennedy Center for Research in Mental Retardation and Human Development.
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