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: 7938129
• 负责人: Javier Contreras
• 金额: $ 7.28万
• 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/7938129
• 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）是一种精神病，发病率高，影响了所有人口的1％至4％。大多数患者的精神症状，生产力失去和功能性持续困难。尽管对双极表型进行了广泛的遗传研究，以及该疾病背​​后的特定基因的一些有趣的联系和结合发现很困难。对BP涉及的遗传基因座的搜索很可能受到疾病的复杂性和定义BP光谱的困难的阻碍。阐明BP遗传结构的主要问题之一是，BP的分类诊断似乎是表型与特定基因型变体之间相关性的预测指标，这有助于个人发展BP的风险。因此，对于解决BP遗传研究中，基因型和表型（内型型）之间介导的过程的诊断状态是必不可少的。这种生物标志物代表了BP基础基础生物过程的窗口。内型型可能代表了一种更简单，可拖延的病因，可以通过对定性表型标记（例如诊断类别）不易获得的强大分析策略进行定量测量和分析。我们已经进行了一项试点研究，以研究BP家族中BPI的候选焦虑定量测量，通过分析遗传力，遗传相关性和与BPI的关联。我们发现，状态和特质焦虑的定量测量是高度遗传的，具有一些遗传因素，并且焦虑特征与BPI有关。当前的建议旨在进一步研究来自类似遗传和文化环境（哥斯达黎加中央山谷人口）的较大BPI样本的较大BPI样本。我们将确定至少有一个被诊断为BPI的个体（通过基于DSMIV的共识诊断）和60个健康无关的对照组，并确定30个新的扩展血统（600个个体）。定量焦虑将通过使用状态特征焦虑清单来评估，并将使用其他相关的人格量表来评估焦虑量表的焦虑量表。我们将通过使用太阳能软件包提供的专门统计分析来测试焦虑是否满足验证标准是BPI的内形型。我们将收集血液标本，超出当前建议的范围：所有受试者（来自我们的试点研究中的660名新人和566名旧受试者）以及QTL链接和关联分析将进行完整的基因组筛查。我们假设我们将确定包含样本中这些定量测量基因的区域，以及BPI焦虑成分的主要作用的特定候选基因。 公共卫生相关性：这项研究提出了BPI的另一种临床定义，并意图解决了其病因的底层遗传难题。对BPI和合并症焦虑的复杂相互作用的理解为连续双极光谱提供了新的诊断范式。提高临床分类的准确性将使这些患者对公共卫生政策有积极作用的治疗方法有益。因此，更有效的卫生资源分配将是追求的，这在社会化的公共卫生系统中至关重要。