Next Generation Diffusion MRI Biomarkers for Prodromal Schizophrenia

项目摘要/摘要 精神分裂症是一种破坏性和衰弱的疾病，影响约1%的人口， 以一系列症状为特征的，包括妄想、幻觉、认知功能受损、情绪 骚乱和社会退缩。对精神分裂症的神经病理学知之甚少，但成像 对其早期阶段的研究有可能确定精神病发病前的最初病理痕迹。 新的研究方法现在允许临床医生调查先兆精神分裂症受试者(前驱症状) 精神病症状减轻，罹患精神分裂症的高危人群。扩散 核磁共振是一种很有前途的前兆成像技术，因为它能持续可靠地识别异常。 在精神分裂症的所有阶段。然而，目前弥散磁共振生物标记物和分析方法受到限制。 对基础微结构病理的敏感性和特异性较差，这构成了进一步 了解精神分裂症的病因，以及药物治疗的新进展。 这项提案的目标是开发工具并应用下一代扩散磁共振生物标记物，如FREE- 水成像，轴突密度，轴突方向弥散，峰度。这些生物标记物改善了 这是目前可用的测量方法的特异性和敏感性，更适合于识别微妙的病理。 我们之前的研究表明，神经发育、神经炎性和神经退行性变 微结构病理与精神分裂症有关。我们假设神经炎是 导致精神症状减弱的显性病理，以及 神经发育改变了大脑的外观或生长方式，可能是精神病的易感因素。 使用下一代扩散磁共振生物标记物可以区分这些微病理，这将 有助于解释它们与减轻的精神病症状之间的联系，并揭示它们在精神病发病中的作用。 大规模研究，如北美前驱症状纵向研究(NAPLS)，已经 收集了大量的CHR数据集，其中包括dMRI数据，这些数据将向我们提供。我们的方法是 利用这些现有的数据并利用它来研究前驱症状的病理相关性， 与之前专注于转换到深圳的风险的研究不同。汇集了前所未有的海量数据 (N&gT；700)提供足够的灵敏度来识别细微的前驱病变。 一个由计算机科学家和临床神经科学研究人员组成的训练有素的团队将致力于开发 新一代扩散磁共振生物标记物的工具，以定位和表征神经生物学 这是前驱症状学的基础。这项研究的结果将对我们的 对精神分裂症初期潜在的生物学机制的理解，将导致 改善了诊断，并可能针对神经炎症等现象进行新的治疗。

Project Summary/Abstract Schizophrenia is a devastating and debilitating disorder that affects about 1% of the population and is characterized by a range of symptoms including delusions, hallucinations, impaired cognitive function, mood disturbances and social withdrawal. Little is known about the neuropathology of schizophrenia, yet imaging studies of its earliest stages have the potential to identify initial pathologic traces preceding psychosis onset. New research approaches now allow clinicians to investigate prodromal schizophrenia subjects (prodromes) who experience attenuated psychotic symptoms, and are at high-risk for developing schizophrenia. Diffusion MRI is a promising imaging technique for prodromes, since it consistently and reliably identifies abnormalities in all stages of schizophrenia. However, current diffusion MRI biomarkers and analysis methods have limited sensitivity and poor specificity to the underlying microstructural pathology, which pose barriers to further understanding the etiology of schizophrenia, and to new developments in pharmacological treatment. The goal of this proposal is to develop tools and apply next generation diffusion MRI biomarkers, such as free- water imaging, neurite density, neurite orientation dispersion, and Kurtosis. These biomarkers improve specificity and sensitivity of currently available measures, and are more suited to identify subtle pathologies. Our previous research suggests that neurodevelopmental, neuroinflammatory and neurodegenerative microstructural pathologies are involved in schizophrenia. We hypothesize that neuroinflammation is the dominant pathology responsible for triggering attenuated psychotic symptoms, and that abnormal neurodevelopment, which changes how the brain appears or grows, may be a predisposition for psychosis. Using next generation diffusion MRI biomarkers can distinguish between these micropathologies, which will help explaining their association with attenuated psychotic symptoms, and reveal their role in psychosis onset. Large-scale studies, such as the North American Prodrome Longitudinal Study (NAPLS), have already collected large datasets of CHR that include dMRI data, and this data will be available to us. Our approach is to leverage from these existing data and utilize it to study the pathological correlates of prodromal symptoms, unlike previous studies that focused on risk for conversion to SZ. The assembled unprecedentedly large data (n>700) provide ample sensitivity to identify subtle prodromal pathologies. A highly trained team of computer scientists and clinical neuroscience researchers will work to develop novel tools for next generation diffusion MRI biomarkers in order to localize and to characterize the neurobiology that underlies prodromal symptomatology. The results of this study will have an important impact on our understanding of biological mechanisms underlying the initial stages of schizophrenia, and will lead to improved diagnosis and possibly new treatments that target such phenomena as neuroinflammation.