Vulnerability to Progression Schizophrenia

描述（由申请人提供）：申请波士顿中心的中心主题， 干预开发和应用研究（CIDAR）是“发展的脆弱性” 精神分裂症”。我们认为该提案有两大优势。首先，我们研究的对象， 疾病的进展阶段，前驱期，首次发作和慢性，给我们一个广泛的 关于表型标记和进展预测因子的观点和大型数据库。此外，委员会认为， 将在一项前瞻性纵向研究中对预防性和首次发病个体进行评价。第二 在我们看来，主要的优势是我们计划将临床、认知、神经成像、电生理学 SZ疾病进展的激素和遗传标记，以了解潜在的 神经回路可能受到干扰。我们通过研究感兴趣的基因的表达来做到这一点， 尸检材料中的特定细胞群，并评估相关 基因与每个项目的进展指数。 四个项目，每个项目都有一名经验丰富的研究者作为PI，都评价了同一组受试者， 从而为疾病进展的标志和预测因素带来多个视角。项目1。“功能 精神分裂症中神经认知退化的解剖学”，使用神经心理学和功能磁共振成像 评价。项目2，“激素、记忆和性对精神分裂症疾病进展的影响”， 评估精神分裂症的激素和性别差异。项目3，“电生理和MRI 灰质标记物和进展的预测因子”，使用事件相关电位（ERP）和MRI灰度 重要的措施，以评估进展，往往结合在这两个领域。项目4，“脆弱性 精神分裂症向白色物质进展”使用白色物质的扩散张量成像评价。 一个长期的历史，以前的成功合作和工作的联合项目，这些项目 PI将促进协同互动，这对于将来自不同领域的数据编织在一起至关重要。 方法和概念领域。 该中心的机制为这项工作带来了附加值，因为没有一个单一的R 01奖可以支持： 翻译基因表达和遗传学奋进的核心，具体联系到每一个 项目的临床研究结果; 2）每个项目所需的大规模受试者招募; 3） 广泛的神经成像工作; 4）将项目的各种技术和水平联系在一起， 分析相同的主题，提供丰富的机会来了解调查结果的相互关系 从不同的领域。

DESCRIPTION (provided by applicant): The central theme of the application for a Boston Center for Intervention Development and Applied Research (CIDAR) is "Vulnerability to Progression in Schizophrenia". We see two major strengths of the proposal. First we study subjects who are at various stages of progression of the disorder, prodromal, first episode and chronic, giving us a broad perspective and large database on phenotypic markers and predictors of progression. Moreover, prodromes and first episode individuals will be evaluated in a prospective longitudinal study. A second major strength, in our view, is our plan to link clinical, cognitive, neuroimaging, electrophysiological, hormonal and genetic markers of SZ disease progression to the understanding of how the underlying neural circuits may be disturbed. We do this by investigating the expression of genes of interest in specific cellular populations in post-mortem material and evaluating genetic association of the relevant genes with progression indices from each Project. Four projects, each with an experienced investigator as PI, all evaluate the same group of subjects so as to bring multiple perspectives on the markers and predictors of progression. Project 1. "Functional anatomy of neurocognitive deterioration in schizophrenia", uses neuropsychological and fMRI evaluations. Project 2, "Hormones, memory & sex effects in illness progression in schizophrenia", evaluates hormones and gender differences in schizophrenia. Project 3, "Electrophysiological and MRI gray matter markers and predictors of progression", uses event-related potentials (ERPs) and MRI gray matter measures to evaluate progression, often conjoint, in these two domains. Project 4, "Vulnerability to white matter progression in schizophrenia" uses diffusion tensor imaging evaluations of white matter. A long-standing history of previous successful collaborations and work on joint projects by these project PIs will facilitate the synergistic interactions essential for knitting together data from the different methodological and conceptual domains. The Center mechanism brings added value to this work since no single R01 award could support: 1) the translational gene expression and genetics endeavor in the cores that specifically links to each Project's clinical research findings; 2) the large-scale subject recruiting needed for each project; 3) the extensive neuroimaging work; 4) the linking together of the Project's diverse technologies and levels of analysis on the same subjects, affording a rich opportunity to understand interrelationships of findings from different domains.