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”。我们看到了该建议的两个主要优点。首先，我们研究了处于疾病进展的不同阶段的受试者，前驱，首发和慢性，为我们提供了一个关于表型标记和进展预测因子的广阔视角和大型数据库。此外，前驱症状和首发个体将在一项前瞻性纵向研究中进行评估。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、激素和遗传标记与潜在神经回路如何受到干扰的理解联系起来。我们通过研究死后物质中特定细胞群体中感兴趣的基因的表达，并通过每个项目的进展指数评估相关基因的遗传关联来做到这一点。

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.