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: 8357317
• 负责人: JOHN P CAPITANIO
• 金额: $ 10.1万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357317
• 关键词: Adolescent; Adrenal Glands; Age; Animals; Anxiety; Asthma; Behavioral; California; Characteristics; Control Animal; Development; Enrollment; Funding; Future; Genetic; Grant; Human; Hydrocortisone; Hypothalamic structure; Immune; Immunologics; Individual; Infant; Intervention; Macaca mulatta; Measures; Mental Depression; Modeling; Monkeys; National Center for Research Resources; Neurologic; Outcome; Pituitary Gland; Predisposing Factor; Predisposition; Primates; Principal Investigator; Prospective Studies; Psychosocial Factor; Research; Research Infrastructure; Resources; Retrospective Studies; Risk; Risk Factors; Sampling; Source; Symptoms; Temperament; United States National Institutes of Health; airway hyperresponsiveness; behavior measurement; cost; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 长期以来，哮喘一直被认为具有重要的社会心理成分。有大量证据表明，诸如焦虑，抑郁和抑制气质之类的社会心理因素与哮喘有关。尽管许多研究使用这些构造与哮喘和非心血管人员进行了对比，但这种方法无法确定这些因素是否易于发展哮喘。然而，少数前瞻性研究确实表明，在未来患哮喘的人中拥有其中一些特征的人更加危险。可以鉴定出诱人的遗传，免疫学和神经系统机制，在发育前和发展哮喘症状之前识别高风险的个体的能力将是巨大的，并且可以提出可能会避免哮喘发展的干预措施。尽管对人类进行此类研究非常困难和昂贵，但这种方法最近被认为具有很大的价值，并且需要数年才能完成。对哮喘项目入学的恒河猴的初步回顾性研究表明，在婴儿期评估的抑制性质和钝化的皮质醇反应性的指标预测哪些动物会发展为幼年的气道高反应性，而不会。在拟议的研究中，我们将在各种哮喘相关的措施上前瞻性地对比两组少年动物进行对比。表现出抑制性气质和钝性皮质醇对婴儿短暂分离的动物将构成我们的“处于危险”样本。第二组将是控制动物，这些动物没有显示这些特征。我们的具体目的是：1）证实我们的回顾性发现，具有钝性皮质醇反应和抑制行为风格的婴儿猴子表现出AIRWAILS AIRWAILS AIRWARES AFIRWAINSS AFERWENSISISIONS作为少年； 2）确定气质差异是否与哮喘相关的免疫测量有关； 3）确定气质差异是否与下丘脑 - 垂体 - 肾上腺活性改变有关； 4）检查婴儿气质如何与少年动物行为功能的当前量度有关，并确定当前功能的度量是否会增加预测哪些动物表现出与哮喘相关的结果的能力。