BRAIN DEVELOPMENT ON ADULTS WITH SCHIZOPHRENIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。磁共振成像显示，正常的大脑发育持续到40岁左右，此时额叶和颞叶的白质体积达到最大。这证实了死后的证据，表明这些大脑区域的髓鞘形成一直持续到40多岁。髓磷脂对正常的脑功能至关重要，因为它能加快轴突传递的速度。髓鞘形成的增加受到良好的调节，并与灰质体积的减少相一致，导致成年期脑容量不变。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，当横断面检查时，成年精神分裂症患者的大脑发育失调，成年期缺乏正常的髓鞘形成。该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患者和正常成年人的灰质和白质体积变化。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，并将检查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，普遍认为是一种固定的、因此无法修复的大脑发育问题导致了所有精神分裂症的观点将被超越。这将改变我们对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物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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.