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: 8270501
• 负责人: Joseph D. Buxbaum
• 金额: $ 30.06万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8270501
• 关键词: Address; Affect; Age; Anisotropy; Anterior; Area; Behavioral; Brain; Brain region; Brodmann' s area; Chronic; Clinical; Cognitive; Competence; Complex; Corpus Callosum; Corpus striatum structure; 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; Maps; Measurement; Measures; Metabolic; Methods; Myelin; Oligodendroglia; Onset of illness; Pathway interactions; Patients; Pattern; Performance; Positron-Emission Tomography; Prefrontal Cortex; 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; gray matter; 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、基底前脑和边缘系统等大脑区域之间的连接性改变 系统被认为是精神分裂症的网络缺陷。联合国系统的多区域方面 假设的连通性问题暗示了白色物质的可能不足， 改变或中断一些特定的大脑回路。精神分裂症患者髓磷脂的全面缺陷可能 也会产生一种分布的多区域赤字模式，与复杂的，不明确的本地化， 精神分裂症的行为和认知紊乱数量、分布和 少突胶质细胞的超微结构完整性，关键白色物质成分，最近在 前额叶皮层在精神分裂症，符合我们原来的扩散张量的研究结果，减少 额部白色物质的各向异性以及我们在该项目的第一个资助期内对此进行的复制。 为了扩展我们对精神分裂症白色物质异常的发现，我们计划了四个项目：1）我们将 完成一项对精神分裂症患者队列进行3年随访扫描的纵向样本研究 并控制我们已经获得的扩散张量和结构图像， 获得3 T纵向样本（240例受试者，125例精神分裂症患者和115例匹配 2）我们还将在32名患者的队列中采集FDG-PET和绝对葡萄糖定量 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，以进一步发展我们的初步研究。 发现精神分裂症患者的白色物质相对代谢率增加，我们将开发探索性体素- 各向异性和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 制定了束追踪程序，以评估扣带回的具体束方向和终止点， 丘脑，纹状体和胼胝体纤维在前额皮质; 4）我们将分享白色物质各向异性， 与项目1、2、3和5以及核心项目B进行容积测量，以促进和宣传其潜力 选择要检查的大脑区域。综合考虑，这些目标将使我们能够获得最可靠的， 有效的、功能不同的、信息丰富的白色物质评估，以确认特定的丘脑-额叶， 精神分裂症患者的额-纹状体和扣带回通路异常