Temperament as a risk factor in a monkey model of asthma susceptibility

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DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The prevalence of asthma is increasing greatly throughout the world, especially in developed countries. Using an experimental animal model that has close parallels to asthma in humans, the proposed project is aimed at identifying individuals that might be at-risk for developing asthma. The eventual goal of this line of research is to identify effective interventions that could be implemented early in life that might pre-empt development of this disease.