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

• 批准号: 10993958
• 负责人: Nina Vanessa Kraguljac
• 金额: $ 65.04万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-12-02 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10993958
• 关键词: Contribution; Glutamate; Excess; Inflammation; Progressive

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.

精神分裂症是一种与细微的白质异常相关的复杂疾病 随着时间的推移。改变与跨症状维度的疾病严重程度有关，总体较差 结果，但没有策略来减弱白质疾病的进展。这主要是因为 潜在的病理生理过程仍然未知。谷氨酸过量和炎症可能是 促成因素，但我们不知道疾病早期是否有一段时间影响白质 或者如果他们在疾病阶段改变白质。 我们建议使用多模式神经影像学来研究60名未经细化的第一集精神病患者， 60例未经药物的慢性精神病患者和120名匹配的健康对照。我们将使用（1）高级 扩散加权成像以测量白质结构完整性，（2）磁共振光谱 测量白质中的谷氨酸能和炎症标记，以及（3）血液样本以测量 外周炎症和谷氨酸能标记，以检验白质完整性缺陷的假设 随着疾病阶段的函数增加，谷氨酸过量和炎症会导致白质 病理。 确定导致渐进性白质赤字的因素有望 改变我们的机械理解并为生物标志物提供针对性药物开发调查的信息 谷氨酸能或抗炎剂的潜力延迟或减弱白质的下降 精神分裂症。

项目成果

Contrasting Case-Control and Normative Reference Approaches to Capture Clinically Relevant Structural Brain Abnormalities in Patients With First-Episode Psychosis Who Are Antipsychotic Naive.

对比病例对照和规范参考方法，以捕获未接受过抗精神病药物的首发精神病患者的临床相关脑结构异常。

• DOI: 10.1001/jamapsychiatry.2022.3010
• 发表时间: 2022
• 期刊: JAMA psychiatry
• 影响因子: 25.8
• 作者: Remiszewski,Natalie;Bryant,JamesEdward;Rutherford,SaigeE;Marquand,AndreF;Nelson,Eric;Askar,Ibrahim;Lahti,AdrienneCarol;Kraguljac,NinaVanessa
• 通讯作者: Kraguljac,NinaVanessa