P4-Structure and function of white mater in schizophrenia

P4-精神分裂症白质的结构和功能

• 批准号: 7659501
• 负责人: MONTE Stuart BUCHSBAUM
• 金额: $ 30.57万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-16 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7659501
• 关键词: Address; Affect; Age; Anisotropy; Anterior; Appendix; Area; Behavioral; Brain; Brain region; Brodmann' s area; Chronic; Clinical; Cognitive; Compatible; Competence; Complex; Corpus Callosum; Corpus striatum structure; Count; DNA; Data; Data Analyses; Diffusion; Diffusion Magnetic Resonance Imaging; Fiber; Funding; Genes; Glucose; Gray unit of radiation dose; Hyperactive behavior; Image; Individual; Internal Capsule; Interruption; Investigation; Lead; Length; Limb structure; Limbic System; Localized; Maps; Measurement; Measures; Metabolic; Methods; Myelin; Numbers; Oligodendroglia; Onset of illness; Pathway interactions; Patients; Pattern; Performance; Positron-Emission Tomography; Prefrontal Cortex; Rate; Relative (related person); Reporting; Resolution; Sampling; Sampling Studies; Scanning; Schizophrenia; Severities; Structure; Symptoms; Thalamic structure; Time; basal forebrain; base; cohort; first episode schizophrenia; follow-up; frontal lobe; interest; programs; sex; volunteer; white matter

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 four projects: 1) we will 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) We will also 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 voxelby- voxel correlations between anisotropy and glucose metabolic rate; 3) We will 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-frental, fronto-striatal and cingulate pathway abnormalities in schizophrenia.

额叶、基底前脑和边缘等大脑区域之间连接的改变 系统已被提议作为精神分裂症的网络缺陷。多区域方面 假设的连接问题暗示白质可能存在缺陷，这可能导致 重新路由或中断一些特定的大脑回路。精神分裂症患者的髓鞘质整体缺乏可能 还产生了一种分布式的多区域赤字模式，与复杂的、不明确本地化的、 精神分裂症的行为和认知紊乱。数量、分布等方面的变化 少突胶质细胞（白质的关键成分）的超微结构完整性最近在 精神分裂症中的前额皮质，与我们最初的弥散张量减少的发现一致 额叶白质的各向异性以及我们在该项目的第一个资助期间对此进行的复制。 为了扩展我们对精神分裂症白质异常的发现，我们计划了四个项目：1）我们将 在一组精神分裂症患者中完成一项纵向样本研究，并进行 3 年的随访扫描 并控制我们已经从已经获得的扩散张量和结构图像 获得的 3T 纵向样本样本（240 名受试者 - 125 名精神分裂症患者和 115 名匹配的 控制）； 2) 我们还将获得 FDG-PET，对 32 人的队列进行绝对葡萄糖定量 未接受药物治疗的精神分裂症患者和 32 名年龄和性别匹配的对照者，以进一步开发我们的初步研究 发现精神分裂症患者白质相对代谢率增加，我们将开发探索性体素- 各向异性与葡萄糖代谢率之间的体素相关性； 3）我们将利用我们最近的 开发了束追踪程序来评估扣带回的特定束方向和终止点， 前额皮质中的丘脑、纹状体和胼胝体纤维； 4）我们将分享白质各向异性和 对项目 1、2、3 和 5 以及核心 B 进行体积测量，以促进和揭示其潜力 选择要检查的大脑区域。总而言之，这些目标将使我们能够获得最可靠、 有效的、功能不同的、信息丰富的白质评估，以确认特定的丘脑-前额叶， 精神分裂症的额纹状体和扣带通路异常。