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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 长期以来，哮喘一直被认为是一个重要的心理社会因素。有相当多的证据表明，心理社会因素，如焦虑、抑郁和压抑的气质与哮喘有关。虽然许多研究对比了使用这些结构的哮喘患者和非哮喘患者，但这种方法无法确定这些因素是否会导致哮喘的发生。然而，少数前瞻性研究确实表明，在早期拥有这些特征的人在未来患哮喘的风险更大。在发育早期和哮喘症状发展之前识别高危个体的能力将是巨大的好处，因为可以识别诱发遗传、免疫学和神经学机制，并开发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，尽管用人类进行这样的研究非常困难和昂贵，而且需要数年时间才能完成。对参加一个哮喘项目的恒河猴进行的一项初步的回溯性研究表明，在婴儿时期评估的抑制气质和皮质醇反应迟钝的指标可以预测哪些动物在青少年时期会出现呼吸道高反应性，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在各种哮喘相关措施上的差异。在婴儿时期对短暂的母体分离表现出抑制的气质和迟钝的皮质醇反应的动物将构成我们的“高危”样本。第二组将是没有表现出这些特征的对照动物。我们的具体目标是：1)前瞻性地确认我们的回顾发现，皮质醇反应迟钝和行为风格受抑的婴儿猴子在青少年时期表现出呼吸道高反应；2)确定气质的差异是否与哮喘相关的免疫措施有关；3)确定气质的差异是否与下丘脑-垂体-肾上腺活动的改变有关；4)研究婴儿的气质与当前对幼年动物的行为功能的测量如何相关，并确定当前功能的测量是否提高了预测哪些动物表现出与哮喘相关的结果的能力。

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.