White Matter Abnormalities in Schizophrenia

描述（由申请人提供）：拟议的山。西奈孔特精神疾病神经科学中心（CCNMD）旨在高度集中精力阐明白色物质、少突胶质细胞和髓鞘在精神分裂症中的作用。这个建议是由越来越多的证据，白色物质异常的精神分裂症在各种领域的科学探索。连接失败已被证明在精神分裂症中起作用。髓鞘形成和那些影响髓鞘形成的因素，如少突胶质细胞的功能，是可能深刻影响神经元连接的关键过程，特别是考虑到少突胶质细胞的弥散分布和与精神分裂症有关的脑区的广泛分布。现在，多条证据表明少突胶质细胞和髓鞘与精神分裂症有关。影像学和神经细胞化学证据，与脱髓鞘疾病的相似性，白色物质中与年龄相关的变化，髓鞘相关基因异常，以及精神分裂症大脑中表现出的少突胶质细胞形态异常，都有助于一种假设，即少突胶质细胞功能障碍甚至死亡，以及随后的髓鞘维持和修复异常，有助于精神分裂症综合征（见概述和具体项目的详细参考资料）。一套广泛的方法和专业知识将被带到承担的问题CCNMD将追求，包括神经解剖学，神经影像学，分子生物学，分子遗传学，神经心理学，现象学，统计学和数据管理。CCNMD由4个核心组成：核心A：行政;核心B：临床;核心C：脑库;核心D：数据管理和统计。CCNMD的项目包括：项目1，将量化精神分裂症患者大脑中少突胶质细胞数量和空间分布的变化，重点是皮质，丘脑和主要的白色物质区域。项目2基于Buxbaum博士实验室的微阵列发现，在相对治疗难治性患者的亚组的背外侧前额叶皮层中，6种髓鞘相关基因的表达降低。项目3检查了参与髓鞘形成的基因，以评估其中一些变异是否参与决定精神分裂症的易感性。项目4带来了强大的神经成像技术-扩散张量成像（DTI）和磁化传递成像（MTI）-精神分裂症的白色物质的研究。项目5将质子磁共振波谱（1 MRS）应用于精神分裂症患者大脑中的白色物质区域。

DESCRIPTION (provided by applicant): The proposed Mt. Sinai Conte Center for the Neuroscience of Mental Disorders (CCNMD) is designed to be a highly focused effort to elucidate the role of white matter, oligodendrocytes and myelin in schizophrenia. This proposal is informed by increasing evidence of white matter abnormalities in schizophrenia in a variety of areas of scientific exploration. A failure in connectivity has been demonstrated to have a role in schizophrenia. Myelination and those factors that affect myelination, such as the function of oligodendroglia, are critical processes that could profoundly affect neuronal connectivity, especially given the diffuse distribution of oligodendrocytes and the widespread distribution of brain regions that have been implicated in schizophrenia. Multiple lines of evidence now converge to implicate oligodendroglia and myelin in schizophrenia. Imaging and neurocytochemical evidence, similarities with demyelinating diseases, age-related changes in white matter, myelin-related gene abnormalities, and morphological abnormalities in the oligodendroglia demonstrated in schizophrenic brains, all contribute to a hypothesis that oligodendroglial dysfunction and even death, with subsequent abnormalities in myelin maintenance and repair, contribute to the schizophrenic syndrome (see overview and specific projects for detailed references). A broad set of methodologies and expertise will be brought to bear on the questions the CCNMD will pursue, including neuroanatomy, neuroimaging, molecular biology, molecular genetics, neuropsychology, phenomenology, statistics, and data management. The CCNMD is comprised of 4 Cores: Core A: Administrative; Core B: Clinical; Core C: Brain Bank; Core D: Data Management and Statistics. The projects of the CCNMD include: Project 1 which will quantify alterations in both numbers of and spatial distribution of oligodendroglia in the brains of schizophrenic patients, focusing on cortical, thalamic, and predominantly white matter areas. Project 2 is based on microarray findings by the laboratory of Dr. Buxbaum of decreased expression of 6 myelin-related genes in the dorsolateral prefrontal cortex of a subgroup of relatively treatment refractory patients. Project 3 examines genes involved in myelination for DNA sequence variation affecting protein sequence and expression in order to assess the possibility that some of these variants are involved in determining susceptibility to schizophrenia. Project 4 brings powerful neuroimaging techniques- diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)- to the study of white matter in schizophrenia. Project 5 applies proton magnetic resonance spectroscopy (1 MRS) to white matter areas in the brains of schizophrenic patients.