Anxiety Trait as a Quantitative Behavioral Marker for Bipolar Disorder.

总结： 双相情感障碍（BP）是一种发病率很高的精神疾病，约占全人类的1 - 4 人口。大多数患者经历持续的精神症状困难，丧失生产力， 功能.尽管对双极表型进行了广泛的遗传研究，并发现了一些有趣的连锁反应， 相关性研究发现识别引起这种疾病的特定基因是困难的。搜索 因为BP涉及的遗传位点可能受到疾病的复杂性和治疗的困难的阻碍， 定义BP频谱。阐明BP遗传结构的主要问题之一是， BP分类诊断似乎是表型和表型之间相关性的不良预测因子。 导致个体发生BP风险的特定基因型变异。因此， 基因型和表型（内表型）之间的介导过程对于解决 BP遗传学研究中家族成员的诊断状态相互矛盾。这些生物标志物代表了 这是一个了解BP背后受遗传影响的生物过程的窗口。内表型可能代表一种 简单易行的病因学，可以通过强大的分析进行定量测量和分析 策略不容易获得的定性表型标记，如诊断类别。我们有 进行了一项试点研究，以调查焦虑的定量测量作为候选内表型， 通过对BP家系BPI的遗传力、遗传相关及与BPI的关联分析，探讨BP家系BPI的遗传规律.我们发现 状态焦虑和特质焦虑的定量测量是高度遗传的，共享一些遗传因素， 焦虑特质与BPI相关。目前的建议旨在进一步研究焦虑特质， 来自相似遗传和文化环境（哥斯达黎加）的BPI扩展家系的较大样本 中央谷人口）。我们将确定30个新的扩展谱系（600个个体）， 1例诊断为BPI的个体（根据DSMIV的一致诊断）和60例健康无关 对照定量焦虑将通过使用状态-特质焦虑量表和其他 自我评定的焦虑相关人格量表将被用于将焦虑表征为潜在的焦虑。我们将测试 焦虑是否符合验证标准，通过使用专门的BPI内表型， 由SOLAR软件包提供的统计分析。我们会收集血液样本 目前建议的范围：将对所有受试者（660名新受试者）进行全基因组筛查 个体和566名老年人的QTL连锁和关联分析。我们 我们假设，我们将确定区域含有基因的具体这些定量措施， 样本，以及具体的候选基因的主要影响的焦虑成分的BPI。

Summary: Bipolar Disorder (BP) is a psychiatric illness with high morbidity, affecting from 1 to 4 % of all human populations. Most patients experience continued difficulty with psychiatric symptoms, lost productivity and functionality. Despite extensive genetic studies of the bipolar phenotype, and some interesting linkage and association findings identification of specific genes underlying the disorder have been difficult. The search for the genetic loci involved in BP has likely been hampered by the complexity of the illness and difficulty in defining the BP spectrum. One of the main problems in elucidating the genetic architecture of BP is the fact that the BP categorical diagnosis appears to be a poor predictor of correlation between the phenotype and the specific genotypic variants which contribute to an individual's risk of developing BP. Hence, indicators of processes mediating between genotype and phenotype (endophenotypes) are necessary to resolve the conflicting diagnostic status of family members in genetic studies of BP. Such biomarkers represent a window into the genetically influenced biological process underlying BP. Endophenotypes may represent a simpler and tractable etiology that can be quantitatively measured and analyzed with powerful analysis strategies not readily available for qualitative phenotypic markers such as diagnostic category. We have conducted a pilot study to investigate a quantitative measure of anxiety as a candidate endophenotype for BPI in BP families, by analyzing the heritability, genetic correlation and association with BPI. We found that quantitative measurements of state and trait anxiety are highly heritable, share some genetic factors and that the anxiety trait is associated with BPI. The current proposal intends to further examine anxiety trait in a larger sample of BPI extended pedigrees from a similar genetic and cultural environment (Costa Rican Central Valley population). We will ascertain 30 new extended pedigrees (600 individuals) with at least one individual diagnosed with BPI (by consensus diagnosis based on DSMIV) and 60 healthy unrelated controls. Quantitative anxiety will be evaluated by using the State-Trait Anxiety Inventory and additional self-rated anxiety related personality scales will be used to characterize anxiety as a potential. We will test whether anxiety fulfill the validation criteria to be an endophenotype for BPI by using specialized statistical analyses provided by SOLAR Software Package. We will collect blood specimens and beyond the scope of the current proposal: a complete genome screen will be conducted for all subjects (660 new individuals and 566 old subjects from our pilot study,) and QTL linkage and association analyses as well. We hypothesize that we will identify regions containing genes specific for these quantitative measures in the sample, as well as specific candidate genes of major effect underlying the anxiety component of BPI.