Vulnerability to Progression Schizophrenia

波士顿干预发展和应用研究中心（CIDAR）申请的中心主题是“精神分裂症进展的脆弱性”。我们认为该提案有两大优势。首先，我们研究了处于疾病进展的各个阶段的受试者，前驱期，首次发作和慢性，为我们提供了关于表型标记物和进展预测因子的广阔前景和大型数据库。此外，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。在我们看来，第二个主要优势是我们计划将SZ疾病进展的临床、认知、神经影像学、电生理学、激素和遗传标记与对潜在神经回路可能受到干扰的理解联系起来。我们通过调查特定细胞群体中感兴趣的基因在死后材料中的表达，并评估相关基因与每个项目进展指数的遗传关联来做到这一点。 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，以便对进展的标志物和预测因素提出多个观点。项目1。“精神分裂症神经认知恶化的功能解剖学”，使用神经心理学和功能磁共振成像评估。项目2，“激素，记忆和性别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 Gray matter marker and predictors of progression”使用事件相关电位（ERP）和MRI灰质测量来评估这两个领域的进展，通常是联合的。项目4，“精神分裂症中白色物质进展的脆弱性”使用白色物质的扩散张量成像评价。 这些项目主要研究者以往在联合项目上的成功合作和工作的长期历史将促进协同互动，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：1）与每个项目的临床研究结果具体相关的核心中的翻译基因表达和遗传学奋进; 2）每个项目所需的大规模受试者招募; 3）广泛的神经影像学工作; 4）将项目的不同技术和对相同主题的分析水平联系在一起，为理解研究结果的相互关系提供了丰富的机会 从不同的领域。

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.