MR Brain Diffusion Tensor Imaging in Schizophrenia

精神分裂症的 MR 脑扩散张量成像

• 批准号: 8921662
• 负责人: Martha E. Shenton
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921662
• 关键词: Acute; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Antipsychotic Agents; Attention; Award; Biological; Biological Markers; Brain; Choline; Chronic; Chronic Schizophrenia; Clinical; Cognitive; Communication; Data; Demyelinations; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease remission; Edema; Electroencephalography; Electrophysiology (science); Etiology; Funding; General Population; Glutamates; Glutathione; Goals; Grant; Healthcare; Inflammation; Intervention; Investigation; Knowledge; Lead; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Methods; Mission; Myelin; N-acetylaspartate; Nature; Nerve Degeneration; Neurobiology; Neurons; Neurotransmitters; Onset of illness; Outcome; Pathologic Processes; Pathology; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Phenotype; Population; Process; Progress Reports; Proliferation Marker; Protons; Psychotic Disorders; Publications; Publishing; Reporting; Resources; Role; Schizophrenia; Specificity; Spectrum Analysis; Speed; Staging; Symptoms; Synapses; Syndrome; Time; Tissues; Water; Work; axon injury; axonal degeneration; base; cellular pathology; early onset; excitotoxicity; extracellular; follow-up; gray matter; improved; in vivo; inflammatory marker; interhemispheric transfer; myelin degeneration; myoinositol; neurochemistry; neuroimaging; neuroinflammation; neurotransmission; novel; psychotic symptoms; public health relevance; tool; transmission process; treatment strategy; white matter; white matter change

 DESCRIPTION (provided by applicant): This application is a competitive renewal for 4 years of funding which extends earlier work conducted during the previous grant period. In this application we will enhance our understanding of the neurobiology of white matter changes in schizophrenia by introducing novel tools and methods that are more specific with respect to underlying pathology. This work is highly relevant to the overall VA mission, as patients with schizophrenia utilize 40% of the VA healthcare resources. Historically, the role of white matter in schizophrenia has been largely overlooked, with the majority of biological hypotheses focused on abnormalities in gray matter. This is despite the fact that schizophrenia is now viewed as a dys-connection syndrome, and that it is white matter that provides long-range communication among neurons. Only recently, with the introduction of diffusion MRI (dMRI), has attention slowly shifted to investigating the roe of white matter in schizophrenia. Nonetheless, findings to date have not led to an understanding of the etiology or to new pharmacological treatment(s), primarily because dMRI measures are nonspecific to underlying microstructural pathology. New methods, however, are more specific with respect to pathology, and based on our preliminary data using free-water derived from dMRI, and magnetic resonance spectroscopy (MRS), we hypothesize that white matter in schizophrenia is compromised by at least two distinct pathological processes that occur at different stages of the disease, i.e., neuroinflammation and neurodegeneration. Here we will use novel tools and methods to identify the neurobiological nature, time course, and functional consequences of specific changes in white matter in schizophrenia. Specifically, we will use several recently developed MRI acquisition and analysis methods, and apply them to both early onset schizophrenia and chronic schizophrenia populations, as well as to matched healthy controls. In terms of biological hypotheses, we predict that: A) early onset schizophrenia is likel associated with pathology (neuroinflammation) affecting extracellular volume observed using dMRI and magnetic resonance spectroscopy indicators of neuroinflammation; B) chronic schizophrenia is likely associated with increasing cellular pathology (neurodegeneration), observed using dMRI and MRS measures; and, C) both neuroinflammation and neurodegeneration have an effect on axonal conduction transmission speed, evinced using an interhemispheric transfer task, and localization of these changes will predict clinical profile. Longitudinal changes will also be evaluated one year later in the early psychosis patients in order to determine progressive changes in white matter over this time period. The investigation of dMRI, MRS, and EEG methods in schizophrenia will lead to novel findings of white matter abnormalities in schizophrenia, including new information about the role of neuroinflammation and neurodegenerative processes that occur at different stages of the disorder, which, in turn, will provide a new perspective on possible treatment interventions that will likely involve anti-inflammatory agents early in the course of illness.

 描述（由申请人提供）： 该申请是4年资金的竞争性续约，可扩展在上一个赠款期间进行的早期工作。在此应用中，我们将通过引入针对潜在病理学更具体的新工具和方法来增强我们对精神分裂症白质变化的神经生物学的理解。这项工作与整体VA任务高度相关，因为精神分裂症患者利用40％的VA医疗保健资源。从历史上看，白质在精神分裂症中的作用在很大程度上被忽略了，大多数生物学假设都集中在灰质的异常上。尽管事实上，精神分裂症现在被视为一种DYS连接综合征，并且是白质在神经元之间提供远距离交流。直到最近，随着扩散MRI（DMRI）的引入，人们的注意力逐渐转移到了精神分裂症中的白质的ROE上。尽管如此，迄今为止的发现并未导致对病因学或新药物治疗的理解，因为DMRI测量值不针对潜在的微结构病理。然而，新方法在病理学方面更为具体，并基于我们的初步数据，使用源自DMRI的自由水和磁共振光谱（MRS），我们假设精神分裂症中的白质是由至少两个不同的病理学过程（即在疾病的不同阶段）（即神经元素化和neurodefenflymation和Neurodefention and Neurodefention和Neurodefeneration）所损害的。在这里，我们将使用新颖的工具和方法来识别精神分裂症中白质特定变化的神经生物学性质，时间过程和功能后果。具体而言，我们将使用几种最近开发的MRI采集和分析方法，并将其应用于早期发作精神分裂症和慢性精神分裂症种群，以及匹配的健康对照。在生物学假设方面，我们预测：a）早期发作精神分裂症就像与使用DMRI和磁共振光谱指标观察到的细胞外体积有关的病理学（神经炎症）相关。 b）使用DMRI和MRS措施观察到慢性精神分裂症可能与细胞病理增加（神经退行性）有关；并且，c）神经炎症和神经退行性变化都对轴突传导速度产生影响，该轴突传播速度使用半球间转移任务表明，这些变化的定位将预测临床特征。在早期的精神病患者中，还将评估纵向变化，以确定这段时间内白质的进行性变化。对精神分裂症中DMRI，MRS和EEG方法的研究将导致精神分裂症中的白质异常的新发现，包括有关神经炎症和神经退行性过程的作用的新信息，这些信息在疾病的不同阶段的作用，而这种疾病的不同阶段，这反过来又可能会涉及治疗疗法的疾病。