This is a proposal for support to continue several years of research on brain structure and function in schizophrenia by the investigator, who has recently moved his laboratory to a new institution. Over the past ten years, under the direction of the investigator and guided by specific hypotheses, a large body of neuroimaging, neuropsychology and ERP data has been collected on patients with schizophrenia and normal controls. These data provide fertile ground for cross-sectional exploratory investigations, testing of additional hypotheses not initially posed, and the continuation of a longitudinal study of the progression of brain dysfunction and dysmorphology in schizophrenia. Based on the investigator's preliminary longitudinal observations, he proposes the hypothesis that schizophrenia is a progressive neurodegenerative disorder.
The specific aims of this proposal are: 1. To test specific hypotheses in cross-sectional studies regarding brain structure and function in schizophrenia with quantitative MRI, neuropsychology, and electrophysiology. What is the pattern of the tissue volume deficits consistently observed in cortical, caudate, cingulate, limbic, and cerebellar regions in patients with schizophrenia? Are there selective relationships between the brain volume abnormalities and specific clinical, neuropsychological, and electrophysiological variables or processes? 2. To test the hypothesis that schizophrenia is a progressive neurodegenerative disorder demonstrable with quantitative MRI, neuropsychology and electrophysiology. Is the progression additive or interactive with age? Is the progression differentially expressed in different brain regions and in different cognitive and electrophysiological measures of brain function?
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