BRAIN DEVELOPMENT ON ADULTS WITH SCHIZOPHRENIA

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 磁共振成像显示，正常的大脑发育持续到40年代中后期，此时额叶和颞叶中的白色物质体积达到最大。这证实了死后的证据表明，这些大脑区域的髓鞘形成持续到40年代。髓鞘对正常的大脑功能至关重要，因为它增加了轴突传输的速度。髓鞘形成的增加受到很好的调节，并与灰质体积的减少一致，导致成年期脑体积恒定。精神分裂症被认为是一种部分由大脑发育异常引起的疾病。我们观察到，当进行横断面检查时，成年精神分裂症患者的大脑发育失调，成年后没有正常的髓鞘形成。本项目将通过重新扫描5年和11年前首次扫描的受试者队列，前瞻性地检查精神分裂症和正常成人的灰色和白色物质体积变化。该项目将更明确地测试精神分裂症患者成年后大脑发育失调的理论，并将研究结果不佳的患者是否特别有可能在成年后遭受这种发育问题。如果得到证实，将超越导致所有精神分裂症的固定且因此不可修复的大脑发育问题的流行概念。这将改变我们如何治疗这种疾病的概念，改变其终身病程的可行性，并将鼓励开发新的药理学干预措施来改善髓鞘形成。

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.