NEUROBIOLOGIC STUDIES OF THE LIMBIC SYSTEM IN AUTISM

Boston University Medical Campus, Boston MA

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Abstract

DESCRIPTION (adapted from applicant's abstract): Relatively few pathological studies of the brain in autism have been reported and a variety of findings in cortical, subcortical and posterior fossa regions have been described. Over the past several years, quantitative and semi-quantitative analyses have been conducted in a small series of autistic brains, studies in comparison with age and sex-matched controls that were processed in whole brain serial section. Abnormalities have been consistently observed in the limbic system, cerebellum and related inferior olive. In the limbic system, the hippocampus, amygdala and entorhinal cortex have shown a small nerve cell size and increased cell-packing density at all ages, consistent with a pattern of developmental curtailment. A different pattern of change had been noted in the vertical limb of the Diagonal Band of Broca, cerebellar nuclei and inferior olive with plentiful and abnormally enlarged neurons in the brains of young autistic subjects, and in adult autistic brains small, pale neurons that are often reduced in number. These findings, combined with reported age-related changes in brain weight, have raised the possibility of a progressive process. However, technological restraints have precluded the determination of total number of neurons in these structures and the use of qualitative and quantitative immunocytochemical techniques. This project will utilize modern immunohistochemical and stereological cell counting techniques to quantitatively analyze selected regions of the limbic system in a series of autistic brains studied in comparison with age and sex-matched controls. Findings will be compared with volumetric magnetic resonance imaging (MRI) analysis in these same brains, and patterns of microscopic abnormality will be correlated with clinical characteristic of each subject based on information derived from medical records and formal interviews with families. Further, studies for evidence of a progressive process, and involvement of selected neurotransmitter systems in the limbic system that have been implicated in the clinical features of autism will be conducted.