Brain structural anomalies in both gray and white matter have been found in patients with schizophrenia. A strong genetic component has also been established for schizophrenia although the mode of inheritance is unknown. We propose that the symptoms of schizophrenia are based on underlying deficits in the axonal connections (white matter) that facilitate language perception and production, particularly through the left superior temporal gyrus including Heschl?s gyrus and the planum temporale. We further hypothesize that a disturbance in this portion of brain could underlie the genetic predisposition for schizophrenia. This hypothesis will be pursued using the newest brain imaging technology available to examine brain white matter integrity, Diffusion Tensor Imaging (DTI) and Magnetization Transfer Imaging (MT). Combined, both methods complement each other and can give information about white matter microstructure that may reflect fiber organization, fiber directional coherence, fiber integrity and/or variations in myelination. Thus, sets of siblings with schizophrenia, their well siblings and pairs of siblings who have no psychotic illness in themselves or their family members will be examined using these imaging techniques. The results from this project will determine whether variation in white matter integrity is familial in both normal individuals and individuals from families afflicted with schizophrenia and whether it is associated with the inherited tendency for schizophrenia. The unraveling of a brain white matter pathology underlying schizophrenia could lead to the establishment of new pharmacologic agents aimed at correcting these defects and protecting the brains of high familial-risk individuals from developing abnormally. Since this hypothesis has not been tested specifically in this way and is speculative, but if correct, may have a great impact on future research, we are using the R21 exploratory mechanism.
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