权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in Psychosis

谷氨酸过量和炎症对精神病进行性白质变化的影响

基本信息

批准号：
10002296
负责人：
Nina Vanessa Kraguljac
金额：
$ 66.54万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-26 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10002296
关键词：
Affect Anti-Inflammatory Agents Antipsychotic Agents Attenuated Blood specimen Choline Chronic Complex Data Diffusion Diffusion Magnetic Resonance Imaging Dimensions Disease Disease Progression Drug Targeting Enrollment Glutamate Metabolism Pathway Glutamatergic Agents Glutamates Glutamine Image Imaging Techniques Inflammation Inflammatory Magnetic Resonance Spectroscopy Measures Mental disorders Modeling Morphology Neurites Outcome Pathology Patients Peripheral Process Psychotic Disorders Reporting Schizophrenia Severity of illness Structure Symptoms Techniques Testing Time Water White Matter Disease density drug development extracellular first episode psychosis indexing inflammatory marker multimodality myoinositol neuroimaging neuroinflammation new therapeutic target peripheral blood public health relevance response targeted biomarker white matter white matter change white matter damage

项目摘要

Schizophrenia is a complex disorder associated with subtle white matter abnormalities that progress over time. Alterations are associated with disease severity across symptom dimensions and worse overall outcomes, but no strategies exist to attenuate white matter disease progression. This is largely because the underlying pathophysiological processes remain unknown. Glutamate excess and inflammation may be contributing factors, but we do not know if there is a period early in the illness where these affect white matter or if they alter white matter across illness stages. We propose to use multimodal neuroimaging to study 60 unmedicated first-episode psychosis patients, 60 unmedicated chronic psychosis patients, and 120 matched healthy controls. We will use (1) advanced diffusion weighted imaging to measure white matter structural integrity, (2) Magnetic Resonance Spectroscopy to measure glutamatergic and inflammatory markers in white matter, and (3) blood samples to measure peripheral inflammatory and glutamatergic markers to test the hypothesis that white matter integrity deficits increase as a function of illness stage and that glutamate excess and inflammation contribute to white matter pathology. Identification of factors that contribute to progressive white matter deficits holds the promise to transform our mechanistic understanding and inform biomarkers for targeted drug development investigating the potential of glutamatergic or anti-inflammatory agents delaying or attenuating white matter decline in schizophrenia.

精神分裂症是一种复杂的疾病，伴有细微的白质异常