Genomic Studies in Bipolar and Major Depression

描述（由申请人提供）：双相情感障碍和抑郁症的神经表型：该中心的申请建议测试两个相关的假设。主要假设是，两种最严重的心境障碍，双相情感障碍（BPD）和重度抑郁症（MDD）在大脑中具有不同的神经表型或生物学特征，如通过单个基因或功能相关基因集合的表达模式中的一组非重叠改变所鉴定的。第二个假设是，一组较小的基因将在这些疾病中显示出共同的改变，并可能代表与情绪障碍的共同脆弱性或这些障碍对大脑的共同影响有关的机制。项目1有助于调查这些假设有三个目的。目标一：确认，表征和研究与对照组和精神分裂症患者相比，与BPD和MDD密切相关的选定基因和途径。用于实现目标1的方法包括qRT-PCR、原位杂交研究、蛋白质印迹蛋白功能研究和SAGE（基因表达的系列分析）。选择了两个结果进行深入表征和研究（MDD中显著失调的FGF系统和与MDD和BPD密切相关的线粒体功能障碍）。目的1将微阵列研究扩展到BPD和MDD与对照组相比的其他边缘和非边缘结构。科学界一致认为边缘系统是BPD和MDD病理生理学中的关键回路。这将是第一个研究评估基因表达的3个边缘结构的控制和情绪障碍患者。目标3将测试盲预测和区分BPD与MDD和SZ的能力。基于由初始队列定义的神经表型，预测和区分BPD，MDD和SZ中的15个BPD，15个MDD和15个对照的新队列。 预测分析中将使用来自以下数据集的信息：BPD和MDD的独特非重叠基因; BPD和MDD中相反方向上显著不同的相同基因; BPD和MDD之间共有的基因; GO和KEGG通路以及BPD和MDD的功能分析。识别验证和复制的基因和途径，可以预测MDD作为不同的BPD将构成一个重大贡献，调查这些疾病的病因，并朝着！确定治疗或预防的新靶点。这些调查与中心的其他项目有许多概念和技术联系，并依赖于所有拟议核心提供的支持。

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.