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 年资助的竞争性更新，延长了之前资助期间进行的早期工作。在该申请中，我们将通过引入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 VA 的整体使命高度相关，因为精神分裂症患者利用了 VA 医疗资源的 40%，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视了。尽管事实上精神分裂症现在被视为一种连接障碍综合征，并且随着扩散的引入，白质才在神经元之间提供了远程通信。 MRI (dMRI) 的注意力逐渐转向研究精神分裂症的白质，然而，迄今为止的发现尚未导致对病因的了解或新的药物治疗，主要是因为 dMRI 测量是不可行的。然而，新方法在病理学方面更加具体，并且根据我们使用来自 dMRI 和磁共振波谱 (MRS) 的游离水的初步数据，我们发现精神分裂症中的白质受到损害。疾病不同阶段发生的至少两种不同的病理过程，即神经炎症和神经变性，在这里我们将使用新的工具和方法来识别神经生物学性质、时间进程和功能后果。具体来说，我们将使用几种最近开发的 MRI 采集和分析方法，并将其应用于早发性精神分裂症和慢性精神分裂症人群，以及匹配的健康对照。预测：A) 早发性精神分裂症可能与影响细胞外容量的病理学（神经炎症）相关，使用 dMRI 和磁共振波谱指标观察神经炎症；使用 dMRI 和 MRS 测量观察到，慢性精神分裂症可能与细胞病理学（神经变性）增加有关；并且，C）神经炎症和神经变性对轴突传导传输速度有影响，使用半球间转移任务证明，并且这些变化的定位将预测临床特征。一年后还将评估早期精神病患者的纵向变化，以确定这段时间内白质的进展变化。精神分裂症的 MRS 和脑电图方法将导致精神分裂症白质异常的新发现，包括有关在疾病的不同阶段发生的神经炎症和神经退行性过程的作用的新信息，这反过来又将为精神分裂症的白质异常提供新的视角。可能的治疗干预措施可能涉及病程早期的抗炎药物。