Anxiety Trait as a Quantitative Behavioral Marker for Bipolar Disorder.

焦虑特质作为双相情感障碍的定量行为标志。

• 批准号: 8304858
• 负责人: Javier Contreras
• 金额: $ 4.86万
• 依托单位: UNIVERSITY OF COSTA RICA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304858
• 关键词: Address; Affect; Anxiety; Architecture; Behavioral; Biocompatible Materials; Biological Markers; Biological Process; Bipolar Disorder; Blood specimen; Candidate Disease Gene; Categories; Classification; Clinical; Communities; Complex; Computer software; Conflict (Psychology); Consensus; Costa Rica; Costa Rican; DNA; DSM-IV; Diagnosis; Diagnostic; Disease; Ensure; Environment; Equipment and supply inventories; Etiology; Evaluation; Family; Family member; Future; Genes; Genetic; Genome; Genome Scan; Genotype; Health Policy; Health Resources; Health system; Heritability; Human; Individual; Interview; Manic; Measurable; Measurement; Measures; Mediating; Mental Depression; Methods; Modeling; Moods; Morbidity - disease rate; Participant; Patients; Personality; Pharmaceutical Preparations; Phenotype; Pilot Projects; Population; Process; Productivity; Psychiatrist; Psychotic Disorders; Public Health; Quantitative Trait Loci; Relative (related person); Residual state; Risk; Sampling; Siblings; Source; Structure; Symptoms; Testing; Time; Training; Validation; Variant; affection; base; clinical Diagnosis; endophenotype; experience; genetic pedigree; improved; instrument; interest; lymphoblastoid cell line; novel diagnostics; trait

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.

概括： 双相情感障碍 (BP) 是一种发病率很高的精神疾病，影响着 1% 到 4% 的人类 人口。大多数患者会经历持续的精神症状困难、生产力下降和 功能。尽管对双相表型进行了广泛的遗传学研究，并发现了一些有趣的联系和 协会的研究结果表明，识别导致该疾病的特定基因非常困难。搜寻 与 BP 相关的基因位点可能受到疾病的复杂性和治疗难度的阻碍 定义 BP 谱。阐明 BP 遗传结构的主要问题之一是这一事实 BP 分类诊断似乎不能很好地预测表型和疾病之间的相关性 导致个体罹患 BP 风险的特定基因型变异。因此，指标 基因型和表型（内表型）之间的介导过程对于解决 BP 遗传学研究中家庭成员的诊断状态相互矛盾。此类生物标志物代表 了解 BP 受遗传影响的生物过程的窗口。内表型可能代表 更简单且易于处理的病因学，可以通过强大的分析进行定量测量和分析 对于定性表型标记（例如诊断类别）来说，策略不易使用。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 通过分析BP家系中BPI的遗传力、遗传相关性以及与BPI的关联性。我们发现 状态焦虑和特质焦虑的定量测量具有高度遗传性，具有一些共同的遗传因素，并且 焦虑特质与 BPI 相关。当前的提案旨在进一步检查焦虑特质 来自相似遗传和文化环境的 BPI 扩展谱系的更大样本（哥斯达黎加 中央谷人口）。我们将确定 30 个新的扩展谱系（600 个人）至少 1 名被诊断患有 BPI 的个体（通过基于 DSMIV 的共识诊断）和 60 名健康的无关个体 控制。定量焦虑将通过使用状态-特质焦虑量表和其他方法进行评估 自评焦虑相关人格量表将用于将焦虑描述为潜在的。我们将测试 通过使用专门的方法，焦虑是否满足作为 BPI 内表型的验证标准 SOLAR软件包提供的统计分析。我们将收集血液样本及其他样本 当前提案的范围：将对所有受试者（660 个新受试者）进行完整的基因组筛查 来自我们试点研究的个体和 566 个老受试者）以及 QTL 连锁和关联分析。我们 假设我们将识别出包含特定于这些定量测量的基因的区域 样本，以及对 BPI 焦虑成分产生主要影响的特定候选基因。