TEMPERAMENT AS A RISK FACTOR IN A MONKEY MODEL OF ASTHMA SUSCEPTIBILITY

气质是哮喘易感性猴子模型的危险因素

• 批准号: 8172598
• 负责人: JOHN P CAPITANIO
• 金额: $ 15.21万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172598
• 关键词: Adolescent; Adrenal Glands; Age; Animals; Anxiety; Asthma; Behavioral; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Control Animal; Development; Enrollment; Funding; Future; Genetic; Grant; Human; Hydrocortisone; Hypothalamic structure; Immune; Immunologics; Individual; Infant; Institution; Intervention; Macaca mulatta; Measures; Mental Depression; Modeling; Monkeys; Neurologic; Outcome; Pituitary Gland; Predisposing Factor; Predisposition; Prospective Studies; Psychosocial Factor; Research; Research Personnel; Resources; Retrospective Studies; Risk; Risk Factors; Sampling; Source; Symptoms; Temperament; United States National Institutes of Health; airway hyperresponsiveness; behavior measurement; infancy; infant temperament; juvenile animal; maternal separation; psychosocial; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma has long been recognized as having a significant psychosocial component. Considerable evidence exists that psychosocial factors, such as anxiety, depression, and inhibited temperament, are associated with asthma. While many studies have contrasted asthmatic and non-asthmatic people using these constructs, such an approach cannot determine whether these factors are predisposing to development of asthma. A handful of prospective studies, however, do suggest that individuals possessing some of these characteristics at an early age are more at-risk for developing asthma in the future. The ability to identify at-risk individuals early in development and prior to development of asthmatic symptoms would be of enormous benefit, in that predisposing genetic, immunologic, and neurologic mechanisms could be identified, and interventions developed that might pre-empt the development of asthma. Such an approach has recently been suggested as having great value, although conducting such research with humans is very difficult and expensive, and would take years to accomplish. A preliminary, retrospective study of rhesus monkeys enrolled in an asthma project demonstrated that indicators of inhibited temperament and blunted cortisol responsiveness, assessed in infancy, predicted which animals would develop airways hyper-responsiveness as juveniles, and which would not. In the proposed study, we will contrast prospectively two sets of juvenile animals on a variety of asthma-relevant measures. Animals that showed inhibited temperament and blunted cortisol responsiveness to brief maternal separation in infancy will comprise our "at-risk" sample. The second set will be control animals that did not show those characteristics. Our specific aims are to: 1) confirm prospectively our retrospective finding that infant monkeys with a blunted cortisol response and an inhibited behavioral style show airways hyper-responsiveness as juveniles; 2) determine whether differences in temperament are associated with asthma-relevant immune measures; 3) determine whether differences in temperament are associated with altered hypothalamic-pituitary-adrenal activity; 4) examine how infant temperament relates to current measures of behavioral functioning in juvenile animals, and determine whether measures of current functioning increase the ability to predict which animals display asthma-related outcomes.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 长期以来，哮喘一直被认为具有重要的社会心理成分。大量证据表明，焦虑、抑郁和性格内向等心理社会因素与哮喘有关。虽然许多研究使用这些结构对哮喘患者和非哮喘患者进行了对比，但这种方法无法确定这些因素是否会诱发哮喘的发生。然而，一些前瞻性研究确实表明，在早期就具有这些特征的人将来患哮喘的风险更大。在发育早期和出现哮喘症状之前识别高危个体的能力将具有巨大的益处，因为可以识别易感遗传、免疫和神经机制，并制定可能预防哮喘发展的干预措施。这种方法最近被认为具有巨大的价值，尽管对人类进行此类研究非常困难且昂贵，并且需要数年时间才能完成。对参加哮喘项目的恒河猴进行的一项初步回顾性研究表明，在婴儿期评估的抑制性情和迟缓的皮质醇反应性指标可以预测哪些动物在幼年时会出现气道高反应性，哪些不会。在拟议的研究中，我们将前瞻性地对比两组幼年动物的各种哮喘相关措施。那些在婴儿期表现出抑制性气质和对短暂母体分离的皮质醇反应迟钝的动物将构成我们的“高危”样本。第二组将是未表现出这些特征的对照动物。我们的具体目标是：1）前瞻性地证实我们的回顾性发现，即皮质醇反应迟钝和行为方式受到抑制的幼猴在青少年时期表现出气道高反应性； 2) 确定气质差异是否与哮喘相关免疫措施有关； 3）确定气质差异是否与下丘脑-垂体-肾上腺活动的改变有关； 4）检查婴儿气质如何与幼年动物当前行为功能测量相关，并确定当前功能测量是否可以提高预测哪些动物表现出哮喘相关结果的能力。