Diffusion Imaging Biomarkers for Risk, Onset and Outcome in Schizophrenia

描述(由申请人提供)： 项目摘要/摘要白质在大脑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脱节综合征，但这种疾病中脑白质异常的确切生物学性质仍不清楚。此外，尽管多篇出版物报道了精神分裂症的脑白质“异常”，但这些发现迄今并未导致对精神分裂症病因学的进一步了解或药物治疗的新进展。这主要是因为成像措施仍然不具有潜在的微结构病理的特异性，而MRI观察到的变化一直被视为灰质病理过程的持续结果，因此不值得进一步研究白质受累的可能性。在本应用中，我们建议超越测量“白质完整性”的范围。我们假设精神分裂症的白质可能受到几个不同的病理过程的损害，这些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的风险、发病和结果的生物标志物。这项提议的总体目标是使用弥散磁共振成像，以及最新的磁共振成像获取和分析方法，并将它们应用于不同的精神分裂症和精神分裂症相关人群(包括回顾性和前瞻性的)。通过这些工具和措施，我们打算测试三个相关、互补的理论：A)精神分裂症患者以及精神分裂症高危人群共有白质特征，这些特征可能与白质几何结构的神经发育障碍有关；B)急性精神病可能与影响细胞外体积的病理(神经炎症)有关；以及C)慢性精神分裂症可能与细胞(髓鞘)病理增加有关。这个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质变化背后的神经生物学，这些变化在精神分裂症的时间进程中经常被报道。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，并提供易感性、精神病、结局的成像生物标记物，以及可用于监测医疗疗效的措施。这个应用程序的独特之处在于，这些工具的组合超越了标准的DTI，并接触到了许多精神分裂症患者，这些工具都可以在那里应用。

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.