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

精神分裂症是一种复杂的疾病与微妙的白色物质异常， 随着时间改变与疾病的严重程度相关，症状维度和整体恶化 结果，但没有策略存在减弱白色物质疾病进展。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 但我们不知道在疾病早期是否有一个时期，这些因素会影响白色物质 或者在疾病的不同阶段改变白色物质。 我们建议使用多模式神经影像学研究60例未经药物治疗的首发精神病患者， 60例未服药的慢性精神病患者和120例匹配的健康对照。我们将使用（1）高级 弥散加权成像，以测量白色物质结构完整性，（2）磁共振波谱 测量白色物质中的谷氨酸能和炎症标志物，以及（3）测量血液样本 外周炎性和血管生成标记物，以检验白色物质完整性缺陷的假设 随着疾病阶段而增加，谷氨酸盐过量和炎症导致白色物质 病理 确定导致进行性白色物质缺乏的因素有望 转变我们的机制理解，并为靶向药物开发研究提供生物标志物 促肾上腺皮质激素能或抗炎剂延迟或减弱白色物质下降的潜力 精神分裂症

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.