WHITE MATTER ABNORMALITIES IN SCHIZOPHRENIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 越来越多的证据表明，异常的皮层连接可能是精神分裂症病理生理学的一个重要因素。 支持性数据来自精神分裂症的研究，有报告称神经活动减少，细胞迁移异常，不同皮质区域体积之间的异常相关性，以及PET研究中激活模式的改变。 虽然白色物质为皮层连接提供了物理基础，但白色物质的体内研究很少，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，其独特地适合于白色物质的研究，因为其可用于量化组织水流动性的大小和方向性（即，自扩散）。 白色（WM）中的结构，如髓鞘，轴突膜，细胞骨架元件和白色束，可以作为水流动性的障碍，导致水分子沿着平行于纤维的路径移动得更远，而不是垂直于这些纤维的路径。 当存在水流动性的方向依赖性时，扩散被描述为各向异性的。 各向异性可以被量化并用于评估白色物质纤维的微观结构组织。 高度规则、有序的纤维将具有高的各向异性;不太有序的纤维将具有较低的各向异性测量。 在10例慢性精神分裂症患者（SZ）和10例正常对照者（NC）的初步研究中，我们使用DTI评估了白色物质各向异性分数（FA）。 发现精神分裂症受试者的白色物质FA显著减少（Lim et all 1999）。 这一发现表明，精神分裂症患者的白色物质微结构组织发生了改变，进一步证明了皮质连接受损。 在这项申请中，我们建议研究精神分裂症患者和正常对照组的MRI和神经认知评估，扩大范围，从我们的初步研究。 具体来说，我们的目标是：1）复制我们的初步发现，减少白色物质各向异性分数（FA）与一组新的精神分裂症（SZ）患者和正常对照（NC）。 我们的假设是：A）作为一个群体，SZ将有不同的白色物质FA比NC。 我们预计深圳的FA会更低。 B）对于SZ，白色物质FA随区域而变化，产前区域异常最大。 2)检查精神分裂症患者白色白质FA的神经认知相关性。 措施将包括从神经认知电池衍生的五个neucocognitive域。 我们的假设是，在SZ组，FA从选定的白色物质区域将与特定的神经认知领域。

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.