INDOLEAMINE METABOLISM IN AUTISM AND MENTAL RETARDATION

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Elevated platelet serotonin in some autistic and mentally retarded children has been a finding repeatedly reported in the literature. The mechanisms underlying this finding and the relationship between peripheral hyperserotonemia and central serotonin metabolism are poorly understood. The possible efficacy of fenfluramine, reported to lower platelet serotonin and improve autistic functioning, makes it particularly timely for a definitive investigation of the mechanisms of platelet hyperserotonemia. A carefully diagnosed group of hyperserotonemic autistic children (HSA) will be compared to age, sex and SES-matched groups of normal serotonemic autistic children (NSA), hyperserotonemic mentally retarded children (HSMR) and normal children. The pathways of platelet serotonin production, storage and clearance will be examined systematically in the children and in their first degree relatives. A subgroup of HSA and NSA children will undergo CSF studies to determine the relationship of central to peripheral serotonin metabolism. Loci of metabolic defects in individual children, their family members, and in the clinical diagnostic groups will be determined. If multiple deficits are present in the same child or clinical group, a profile of metabolic dysfunction will be established. Fenfluramine, as part of multi-center collaborative project, will be administered to a selected population of children with autism. The studies will address the biochemical mechanisms responsible for hyperserotonemia, its familial or non-familial nature, the clinical features distinguishing hyperserotonemic autistic from normoserotonemic autistic children, the relationship of peripheral to central serotonin metabolism and the effects of lowering platelet serotonin on clinical symptoms of autism.