This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Magnetic resonance imaging has shown that normal brain development continues into the mid-to-late 40's when maximal white matter volumes are reached in the frontal and temporal lobes. This confirms postmortem evidence suggesting that myelination of these brain areas continues into the 40's. Myelin is crucial for normal brain function because it increases the speed of axonal transmission. The increase in myelination is well regulated and occurs in concert with a decrease in gray matter volume resulting in a constant brain volume in adulthood. Schizophrenia is believed to be a disease caused in part by abnormal brain development. We observed that when examined crossectionally, brain development was dysregulated in adult schizophrenic subjects with an absence of normal myelination in adulthood. This project will examine gray and white matter volume changes in schizophrenia and normal adults prospectively by rescanning cohorts of subjects that were initially scanned 5 and 11 years ago. The project will more definitively test the theory that in schizophrenia, brain development is dysregulated in adulthood and will examine whether patients that have a poor outcome are particularly likely to suffer from this developmental problem in adulthood. If confirmed, the prevailing concept of a fixed and therefore unreparable brain developmental problem causing all schizophrenia will be surpassed. This will change our concept of how we could treat this illness, the feasibility of changing its lifelong course, and would encourage the development of novel pharmacologic interventions to improve myelination.
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