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: 8118483
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118483
• 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; public health relevance; trait

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This study proposes an alternative clinical definition of BPI and intents to address the underling genetic puzzle of its etiology. The understanding of the complex interplay of BPI and comorbid anxiety raise a new diagnostic paradigm for the continuum bipolar spectrum. Improving accuracy in clinical classification will benefit the therapeutical approach for these patients with positive effect in public health policies. Thus, a more efficiently distribution of health resources will be pursuit which is crucial in a Socialized Public Health System like in Costa Rica.

描述（由申请人提供）：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% 的人口。大多数患者会经历持续的精神症状困难、生产力和功能丧失。尽管对双相情感障碍表型进行了广泛的遗传学研究，并发现了一些有趣的连锁和关联发现，但识别该疾病背后的特定基因仍然很困难。由于疾病的复杂性和定义血压谱的困难，对与血压相关的基因位点的探索可能受到阻碍。阐明 BP 遗传结构的主要问题之一是，BP 分类诊断似乎不能很好地预测表型和导致个体患 BP 风险的特定基因型变异之间的相关性。因此，基因型和表型（内表型）之间中介过程的指标对于解决 BP 遗传学研究中家庭成员相互矛盾的诊断状态是必要的。这些生物标志物代表了了解 BP 受遗传影响的生物过程的一个窗口。内表型可能代表一种更简单且易于处理的病因学，可以使用强大的分析策略进行定量测量和分析，而定性表型标记（例如诊断类别）则不易使用。我们进行了一项试点研究，通过分析遗传性、遗传相关性以及与 BPI 的关联，研究焦虑的定量测量作为 BP 家族中 BPI 的候选内表型。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。目前的提案旨在进一步研究来自相似遗传和文化环境（哥斯达黎加中央山谷群体）的更大 BPI 扩展谱系样本的焦虑特征。我们将确定 30 个新的扩展谱系（600 名个体），其中至少有 1 名个体被诊断为 BPI（通过基于 DSMIV 的共识诊断）和 60 名健康的无关对照。定量焦虑将通过使用状态-特质焦虑量表进行评估，并且额外的自评焦虑相关人格量表将用于将焦虑表征为潜在的。我们将使用 SOLAR 软件包提供的专门统计分析来测试焦虑是否满足 BPI 内表型的验证标准。我们将收集血液样本，超出当前提案的范围：将对所有受试者（我们的试点研究中的 660 个新个体和 566 个老受试者）进行完整的基因组筛查，以及 QTL 连锁和关联分析。我们假设我们将识别出包含样本中这些定量测量特异基因的区域，以及对 BPI 焦虑成分产生主要影响的特定候选基因。 公共健康相关性：本研究提出了 BPI 的替代临床定义，并旨在解决其病因学的潜在遗传难题。对 BPI 和共病焦虑复杂相互作用的理解为连续双相谱提出了新的诊断范式。提高临床分类的准确性将有利于这些患者的治疗方法，对公共卫生政策产生积极影响。因此，更有效地分配卫生资源将是我们追求的目标，这对于哥斯达黎加这样的社会化公共卫生体系至关重要。