WHITE MATTER ABNORMALITIES IN SCHIZOPHRENIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 越来越多的证据表明，皮质连接异常可能是精神分裂症病理生理学中的一个重要因素。支持数据来自精神分裂症的研究，有报道称神经纤维减少，细胞异常迁移，不同皮质区域体积之间的异常相关性，以及PET研究中的激活模式改变。尽管白质为大脑皮层的连接提供了物理基础，但目前对白质的活体研究很少，可能是因为缺乏适当的工具。 扩散张量成像(DTI)是一种磁共振成像(MRI)方法，它可以在三维上量化组织水流动性(即自扩散)的大小和方向性，因此特别适合于白质的研究。白质(WM)中的结构，如髓鞘、轴突膜、细胞骨架元素和白质束，可以作为水流动的障碍，导致水分子沿着平行于纤维的路径而不是垂直于这些纤维的路径移动得更远。当水的流动性存在方向依赖性时，扩散被描述为各向异性。各向异性可以被量化并用于评估白质纤维的微结构组织。高度规则、有组织的纤维将具有较高的各向异性；组织较差的纤维将具有较低的各向异性度量。在10例慢性精神分裂症患者(SZ)和10例正常对照(NC)的初步研究中，我们使用弥散张量成像(DTI)评估脑白质分数各向异性(FA)。精神分裂症受试者的脑白质FA显著降低(Lim Et All 1999)。这一发现表明，精神分裂症患者的脑白质微结构组织发生了变化，为皮质连接性受损提供了进一步的证据。 在这一应用中，我们建议用MRI和神经认知评估来研究精神分裂症患者和正常对照，扩大了我们初步研究的范围。具体地说，我们的目标是：1)在一组新的精神分裂症(SZ)患者和正常对照组(NC)中重复我们最初发现的白质部分各向异性(FA)减少。我们的假设是：a)作为一个群体，SZ的白质FA与NC不同。我们预计深圳的FA会更低。B)对于SZ，白质FA会因胎儿期异常最严重的地区而异。2)探讨精神分裂症患者脑白质FA的神经认知相关性。这些措施将包括从神经认知电池派生的五个新认知领域。我们的假设是，在SZ组中，来自选定白质区域的FA将与特定的神经认知领域相关。

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. There is converging evidence that abnormal cortical connectivity may be an important factor in the pathophysiology of schizophrenia. Supporting data have come from studies of schizophrenia, with reports of decreased neuropil, aberrant cell migration, abnormal correlations between volumes of different cortical regions, and altered activation patterns from PET studies. Although white matter provides the physical foundation for cortical connectivity, there has been little in vivo study of white matter, perhaps because of lack of appropriate tools. Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) method which is uniquely suited to the study of white matter because it can be used to quanitify the magnitude and directionality of tissue water mobility (i.e., self-diffusion) in three dimensions. Structures in white matter (WM), such as myelin sheaths, axon membranes, cytoskeletal elements and white matter tracts, can act as barriers to water mobility, causing water molecules to move farther along paths that are parallel to fibers rather than those that are perpendicular to these fibers. When there is a directional dependence of water mobility, the diffusion is described as being anisotropic. The anisotropy can be quantified and used to assess the microstructural organization of white matter fibers. Highly regular, organized fibers will have high anisotropy; less well-organized fibers will have lower anisotropy measures. In a preliminary study of 10 chronic schizophrenic subjects (SZ) and 10 normal controls (NC), we used DTI to assess white matter fractional anisotropy (FA). The white matter FA was found to be significantly reduced in schizophrenic subjects (Lim et all 1999). This finding suggests that white matter microstructure organization is altered in schizophrenia, providing further evidence of compromised cortical connectivity. In this application, we propose to study schizophrenia patients and normal controls with MRI and neurocognitive assessments, expanding the scope from our preliminary study. Specifically, our aims are to: 1) Replicate our initial finding of decreased white matter fractional anisotropy (FA) with a new group of schizophrenic (SZ) patients and normal controls (NC). Our hypotheses are: A) As a group, SZ will have different white matter FA than NC. We anticipate the FA in SZ to be lower. B) For the SZ, white matter FA will vary by region with greatest abnormality in the prenatal region. 2) Examine the neurocognitive correlates of white matter FA in schizophrenia. Measures will include five neucognitive domains derived from a neurocognitive battery. Our hypothesis is that within the SZ group, FA from selected white matter regions will be correlated with specific neurocognitive domains.