Emerging evidence suggest that abnormalities in oligodendroglia may lead to white matter pathology that may contribute to the disease processes of schizophrenia (Please see overview of the CCNMD proposal). In this project, we propose to evaluate several neurochemicals that have been shown to be abnormal in white matter diseases using proton magnetic resonance spectroscopy (1H MRS). Specifically, N-acetyl compounds (NA), a marker of neuronal density or injury, choline-compounds (CHO), reflective of cell membrane injury and demyelination, and myo-inositol (MI), a marker of glial response, will be measured. We will perform MRS on 40 chronic schizophrenic patients and 40 age matched control subjects, represented in each decade of life from 20-80 years to assess abnormalities in cerebral metabolites in schizophrenic brains compared to age-matched normal controls. These subjects will be followed with 1H MRS over a 3-4 year period to evaluate for possible progression of white matter changes. As discussed in Project 4, based on prior controlled longitudinal neuroimaging studies, we believe that a 3-4 year period will be sufficient to observe the progression of white matter changes in some of the schizophrenic patients, even if the progression of the disease might be somewhat different among patients with different disease severity and symptomatology. In addition, a sample of first break schizophrenic patients (n = 40) will be scanned to detect possible white matter changes present at the beginning of the illness. These first break patients will be followed up clinically to allow a look back at original scans for predictors of outcome as measured by days in the hospital, which will be determined in a prospective manner by the Clinical Core (see Project 4 for detailed description of subjects). Taken together, the cerebral metabolite measurements (on 1H MRS), and anisotropy measurements (diffusion MRI) and magnetization transfer ratios (MTI) from project 4, should provide in vivo evidence as to whether white matter abnormalities / demyelination occur in patients with schizophrenia.
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