STRUCTURE AND FUNCTION OF WHITE MATTER IN SCHIZOPHRENIA

精神分裂症白质的结构和功能

• 批准号: 7953660
• 负责人: MONTE Stuart BUCHSBAUM
• 金额: $ 1.76万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953660
• 关键词: Age; Anisotropy; Area; Behavioral; Brain; Brain region; Clinical Research; Cognitive; Complex; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Diffusion; Fiber; Funding; Glucose; Grant; Image; Institution; Interruption; Lead; Limbic System; Measures; Metabolic; Myelin; Oligodendroglia; Pathway interactions; Patients; Pattern; Prefrontal Cortex; Relative (related person); Reporting; Research; Research Personnel; Resources; Sampling; Sampling Studies; Scanning; Schizophrenia; Source; Structure; Thalamic structure; United States National Institutes of Health; basal forebrain; cohort; follow-up; frontal lobe; programs; sex; white matter

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.

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。 额叶、基底前脑和边缘系统等脑区之间的连接改变被认为是精神分裂症的网络缺陷。假设的连接问题的多区域方面暗示了白色物质的可能缺陷，这可能导致一些特定的大脑回路的重新路由或中断。精神分裂症中髓鞘的整体缺陷也可能产生一种与精神分裂症中复杂的、不明确的定位、行为和认知紊乱相一致的分布式多区域缺陷模式。最近有报道称，精神分裂症患者的前额叶皮质中，少突胶质细胞（白色物质的关键成分）的数量、分布和超微结构完整性发生了改变，这与我们最初的弥散张量研究结果一致，即额叶白色物质的各向异性减弱，以及我们在本项目第一个资助期的重复研究结果。 为了扩展我们对精神分裂症白色物质异常的发现，我们计划： 1)在精神分裂症患者和对照组队列中完成纵向样本研究，随访扫描3年，其中我们已经从已经采集的3 T纵向样本样本（240名受试者- 125名精神分裂症患者和115名匹配对照）中采集了弥散张量和结构图像; 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者进行FDG-PET绝对葡萄糖定量，以进一步发展我们最初发现的精神分裂症患者白色物质相对代谢率增加，我们将探索性地建立各向异性和葡萄糖代谢率之间的逐体素相关性; 3)利用我们最近开发的束追踪程序来评估前额叶皮层中扣带、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以及核心B共享白色物质各向异性和体积测量，以便促进和告知他们潜在的待检查脑区的选择。总之，这些目标将使我们能够获得最可靠的，有效的，功能不同的，和信息丰富的白色物质的评估，以确认特定的丘脑-额叶，额叶-纹状体和扣带回通路异常的精神分裂症。