Genomic Studies in Bipolar and Major Depression

描述(由申请人提供)：双相情感障碍和抑郁障碍的神经表型：中心申请建议测试两个相关的假说。主要的假设是，两种最严重的情绪障碍，双相情感障碍(BPD)和严重抑郁障碍(MDD)在大脑中有不同的神经表型或生物学特征，这是通过单个基因或功能相关基因集合的表达模式的一组不重叠的变化来识别的。第二种假设是，一组较小的基因将显示出这些疾病的共同变化，可能代表了与常见的情绪障碍易感性或对大脑的共同影响有关的机制。项目1对这些假说的研究有三个目的。目的I：以对照组和精神分裂症患者为对照，确认、鉴定和研究与BPD和MDD密切相关的基因和通路。实现目标1目标的方法包括定量逆转录聚合酶链式反应、原位杂交研究、蛋白质印迹功能研究和SAGE(基因表达系列分析)。有两个发现被选中进行深入的描述和研究：成纤维细胞生长因子系统在MDD和线粒体功能障碍中显着失调，而线粒体功能障碍与MDD和BPD密切相关。目的与对照组相比，L将基因芯片研究扩展到BPD和MDD患者额外的边缘和非边缘结构。科学界已达成共识，认为边缘系统是BPD和MDD病理生理过程中的关键回路。这将是第一个评估对照组和情绪障碍患者3个边缘结构中基因表达的研究。目标3将测试盲目预测和区分bpd与MDD和SZ的能力。根据初始队列定义的神经表型，在新的队列中预测和区分BPD、MDD和SZ，新队列包括15个BPD、15个MDD和15个对照。从以下数据集获得的信息将被用于预测分析：BPD和MDD的独特的非重叠基因；BPD和MDD的相同基因在相反方向上显著不同；BPD和MDD之间共有的基因；BPD和MDD的GO和KEGG通路以及BPD和MDD的功能分析。识别可以预测MDD与BPD不同的有效和复制的基因和途径将对研究这些疾病的病因和走向做出重大贡献！为他们的治疗或预防确定新的目标。这些调查与中心的其他项目有许多概念和技术上的联系，并取决于所有拟议核心所提供的支持。

DESCRIPTION (provided by applicant): Neural Phenotypes in Bipolar & Depressive Disorders: The Center application proposes to test two, related hypotheses. The primary hypothesis is that two of the most serious mood disorders, bipolar disorder (BPD) land major depressive disorder (MDD) have distinct neural phenotypes or biological signatures in the brain as identified by a set of non-overlapping alterations in the pattern of expression of individual genes or functionally related ensembles of genes. The secondary hypothesis is that a smaller set of genes will show alterations in common in these diseases and may represent mechanisms related to common vulnerability to mood disorders or a common impact to those disorders on the brain. Project 1 contributes to the investigation of these hypotheses with three Aims. Aim I: Confirm, characterize and investigate selected genes and pathways which are strongly implicated in BPD and MDD contrasted with controls and schizophrenics. Methods to be employed to achieve the goals of Aim 1 include qRT -PCR, in situ hybridization studies, Western blot protein function studies and SAGE (serial analyses of gene expression). Two findings have been selected for in-depth characterization and study (The FGF system which was significantly dysregulated in MDD and mitochondrial dysfunction which is strongly implicated in both MDD and BPD). Aim l will extend the microarray studies to additional limbic and non-limbic structures in BPD and MDD contrasted with controls. There is scientific consensus that the limbic system is a key circuit in the pathophysiology of BPD and MDD. This will represent the first study evaluating gene expression in 3 limbic structures in controls and mood disorder patients. Aim 3 will test the ability to blindly predict and discriminate BPD from MDD and SZ. Based on the neural phenotypes defined by the initial cohorts, predict and discriminate BPD, MDD from SZ in a new cohort of 15 BPD, 15 MDD and 15 controls. Information derived from the following sets of data will be utilized in the predictive analyses: Unique non- overlapping genes for BPD and MDD; the same genes significantly different in opposite directions in BPD and MDD; genes shared in common between BPD and MDD; GO and KEGG pathway and function analyses of BPD and MDD. The identification of validated and replicated genes and pathways that can predict MDD as distinct from BPD will constitute a major contribution to investigating the etiology of these disorders and toward! identifying novel targets for their treatment or prevention. These investigations have many conceptual and technical links with other Center projects and depend on the support provided by all of the proposed Cores.