Diffusion Imaging Biomarkers for Risk, Onset and Outcome in Schizophrenia

描述（由申请人提供）： 项目摘要/摘要白色物质在大脑的交流和连接中起着至关重要的作用。虽然精神分裂症被假设为一种分离综合征，但这种疾病中白色物质异常的确切生物学性质仍然未知。此外，虽然多篇出版物报道了精神分裂症的白色物质“异常”，但迄今为止这些发现尚未导致对精神分裂症病因学的进一步理解或药物治疗的新进展。这主要是因为影像学测量对潜在的显微结构病理学仍无特异性，并且MRI观察到的变化被视为灰质病理过程的持续结果，因此不值得进一步探讨白色物质受累的可能性。在本申请中，我们提出超越测量“白色物质完整性”。我们假设精神分裂症的白色物质可能受到几种不同病理过程的影响，这些病理过程可以在疾病的不同阶段观察到（有些甚至在临床症状出现之前），因此可能构成精神分裂症风险，发病和结局的生物标志物。本提案的总体目标是使用弥散MRI，沿着最新的MRI采集和分析方法，并将其应用于不同的精神分裂症和精神分裂症相关人群（回顾性和前瞻性）。通过这些工具和措施，我们打算测试三个相关的，互补的理论：A）精神分裂症患者以及有发展精神分裂症风险的受试者共享白色物质特征，这可能与白色物质几何学的神经发育中断有关; B）急性精神病可能与病理学相关。C）慢性精神分裂症可能与增加的细胞（髓磷脂）病理学相关。由计算机科学家和临床神经科学研究人员组成的团队将致力于定位和表征白色物质变化的神经生物学基础，这些变化是沿着精神分裂症的时间进程经常报告的。这项研究的结果将对我们理解精神分裂症的潜在机制产生重要影响，并提供可用于监测药物治疗疗效的脆弱性，精神病，结果和措施的成像生物标志物。这个应用程序的独特之处在于它集合了超越标准DTI的工具，并访问了许多精神分裂症人群，这些工具都可以应用于这些人群。

DESCRIPTION (provided by applicant): Project Summary/Abstract White matter plays a critical role in brain communication and connectivity. While schizophrenia has been hypothesized to be a dis-connection syndrome, the exact biological nature of white matter abnormalities in this disease is still unknown. Furthermore, while multiple publications report white matter "abnormalities" in schizophrenia, those findings to date have not lead to further understanding of schizophrenia etiology or new developments in pharmacological treatment. This is primarily because imaging measures remain nonspecific to the underlying microstructural pathology, and changes observed with MRI have been viewed as an ongoing consequence of gray matter pathological processes, thus not worth pursuing the possibility of white matter involvement further. In this application we propose to go beyond measuring "white matter integrity". We hypothesize that white matter in schizophrenia may be compromised by several, distinct pathological processes that can be observed at different stages of the disease (some even before the presence of clinical symptoms), and thus could potentially constitute biomarkers of risk, onset, and outcome of schizophrenia. The overall goal of this proposal is to use Diffusion MRI, along with the newest MRI acquisition and analysis methods, and to apply them to distinct schizophrenia and schizophrenia related populations (both retrospectively as well as prospectively). With these tools and measures, we intend to test three related, complementary theories: A) Schizophrenics as well as subjects at risk for developing schizophrenia share white matter signatures that may be related to neurodevelopmental disruptions of white matter geometry; B) acute psychosis is likely associated with a pathology (neuroinflammation) affecting the extracellular volume; and C) chronic schizophrenia is likely associated with increasing cellular (myelin) pathology. The assembled team of computer scientists and clinical neuroscience researchers will work to localize and to characterize the neurobiology that underlies white matter changes which are frequently reported along the time course of schizophrenia. The results of this study will have an important impact on our understanding of mechanisms underlying schizophrenia, and provide imaging biomarkers of vulnerability, psychosis, outcome, and measures that can be used to monitor the efficacy of medical treatment. What makes this application unique is the assembly of tools that go beyond standard DTI, and access a number of schizophrenia populations, where these tools can be all applied.