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.

大脑区域之间的连通性改变，例如额叶，基底前脑和边缘 已提出系统作为精神分裂症的网络缺陷。多区域的各个方面 连通性的假设问题暗示白质可能的赤字可能导致 许多特定的脑电路的重新路由或中断。精神分裂症的髓磷脂赤字可能 还会产生分布式多区域缺陷的模式 精神分裂症的行为和认知混乱。数量，分布和 少突胶质细胞的超微结构完整性，关键的白质成分，最近在 精神分裂症的前额叶皮质，与我们的原始扩散张量的发现一致 在本项目的第一个资金期间，额叶白质和我们对此的复制。 为了扩展我们在精神分裂症中对白质异常的发现，我们计划了四个项目：1）我们将 在精神分裂症患者的队列中完成一项纵向样本研究，并进行后续扫描3年 并控制我们已经从已经获得的扩散张量和从已有的结构图像中获取的地方 获得的3T纵向样品样本（240名受试者-125例精神分裂症患者和115例匹配 控件）; 2）我们还将在32个队列上获得具有绝对葡萄糖定量的FDG-PET 精神分裂症和32例年龄和性别匹配的对照的未经药物的患者进一步发展我们的初始 在精神分裂症中发现白质相对代谢率增加的发现，我们将发展探索性voxelby- 各向异性和葡萄糖代谢率之间的体素相关性； 3）我们将利用最近的 开发的道路跟踪程序，以评估特定的道路方向和终止点的扣留点， 前额叶皮层中的丘脑，纹状体和callosal纤维； 4）我们将分享白质各向异性和 通过项目1、2、3和5和核心B进行的体积措施，以促进并告知其潜力 选择要检查的大脑区域。综上所述，这些目标将使我们获得最可靠的， 有效，功能不同且内容丰富的白质评估，以确认特定的丘脑 - 毛发， 精神分裂症的额叶和扣带回途径异常。