STRUCTURE AND FUNCTION OF WHITE MATTER 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。 精神分裂症患者的大脑区域如额叶、基底前脑和边缘系统之间的连通性改变被认为是网络缺陷。假设的连通性问题的多个区域方面意味着白质可能存在缺陷，这可能导致一些特定的大脑回路改变路线或中断。精神分裂症患者髓鞘的全球缺陷也可能产生一种分布的多区域缺陷模式，与精神分裂症患者复杂的、不明确定位的行为和认知障碍相适应。最近在精神分裂症患者的前额叶皮质中发现了少突胶质细胞的数量、分布和超微结构完整性的改变，这与我们最初关于额叶白质各向异性减弱的扩散张量发现一致，并在本项目的第一个资助期重复了这一发现。 为了扩大我们对精神分裂症患者脑白质异常的发现，我们计划： 1)完成一项纵向样本研究，对一组精神分裂症患者和对照组进行3年的随访扫描，其中我们已经从3T纵向样本中获得了扩散张量和结构图像(240名受试者--125名精神分裂症患者和115名匹配的对照组)； 2)对32名未服药的精神分裂症患者和32名年龄和性别匹配的对照组进行FDG-PET绝对葡萄糖定量。为了进一步发展我们最初发现的精神分裂症患者脑白质相对代谢率增加的发现，我们将建立各向异性与葡萄糖代谢率之间的探索性体素-体素相关性； 3)利用我们最近开发的束跟踪程序来评估前额叶皮质中扣带、丘脑、纹状体和胼胝体纤维的特定束方向和终止点；4)我们将与项目1、2、3和5以及Core B共享白质各向异性和体积测量，以帮助并告知他们潜在的要检查的脑区选择。综上所述，这些目标将使我们能够获得最可靠、有效、功能不同和信息量最大的白质评估，以确认精神分裂症患者特定的丘脑-额叶、额叶-纹状体和扣带回通路异常。

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. Alterations in connectivity among brain regions such as the frontal lobe, basal forebrain and limbic system have been proposed as network deficits in schizophrenia. The multiregional aspects of the hypothesized problems in connectivity implicate a possible deficit in white matter that could lead to the rerouting or interruption of a number of specific brain circuits. A global deficit in myelin in schizophrenia may also produce a pattern of distributed multiregional deficits compatible with the complex, not clearly localizing, behavioral and cognitive disorganization in schizophrenia. Alteration in numbers, distribution, and ultrastructural integrity of oligodendrocytes, key white matter components, has recently been reported in the prefrontal cortex in schizophrenia, consistent with our original diffusion tensor findings of diminished anisotropy in frontal white matter and our replication of this in the first funding period of this project. To extend our findings of white matter abnormalities in schizophrenia we plan to: 1) complete a longitudinal sample study with follow-up scans 3 yrs in a cohort of patients with schizophrenia and controls where we have already acquired diffusion tensor and structural images from the already acquired sample of 3T longitudinal sample (240 subjects - 125 patients with schizophrenia and 115 matched controls); 2) acquire FDG-PET with absolute glucose quantification on a cohort of 32 unmedicated patients with schizophrenia and 32 age- and sex-matched controls to further develop our initial finding of increased white matter relative metabolic rate in schizophrenia, we will develop exploratory voxel-by-voxel correlations between anisotropy and glucose metabolic rate; 3) exploit our recently developed tract tracing programs to assess the specific tract directions and termination points for cingulate, thalamic, striatal, and callosal fibers in the prefrontal cortex; 4) We will share white matter anisotropy and volumetric measures with Projects 1, 2, 3 and 5 and Core B in order to facilitate and inform their potential choice of brain areas to be examined. Taken together, these aims will allow us to obtain the most reliable, valid, functionally different, and informative white matter assessments to confirm specific thalamo-frontal, fronto-striatal and cingulate pathway abnormalities in schizophrenia.