This is a revised application of 1K01MH01554-01. Stress has profound, adverse consequences on mental and physical health. However, little is known about how stress affects health. Emerging evidence suggests that sleep may signal vulnerability to, and/or play a causal role in, the adverse health consequences of stress. This Mentored Research Scientist Development Award (MRSDA) study will evaluate the role of sleep in the stress-health relationship. I hypothesize that stress interferes with sleep and that stress-related sleep disruptions will be associated with subsequent declines in mental and physical health. I further hypothesize that intrusive thoughts and avoidance behaviors are one pathway whereby stress interferes with sleep. A longitudinal research design with be used to examine the impact of stress and sleep on subsequent indices of mental and physical health. Subjects will include 89 spouses of recent organ transplant recipients and a smaller comparison group (n=35) of individuals with healthy spouses. Psychobiological measures of stress, sleep, and health will be collected quarterly over a 12-month period. Stress is hypothesized to most strongly interfere with subjective sleep quality and EEG-assessed decrements in sleep continuity (e.g., more awakenings from sleep) and slow-wave sleep. Greater degree of sleep disruption will, inturn, significantly predict subsequent health outcomes including elevated levels of symptom reporting, increased health care utilization, greater psychiatric morbidity and medical burden, and poorer immune function. Furthermore, intrusive thoughts and avoidance behaviors will contribute to the effects of stress on sleep (e.g., subjective sleep quality and EEG-assessed indices of sleep continuity and slow-wave sleep). Longitudinal assessment of psychobiological relationships among stress, sleep, and health outcomes in the proposed study represents the first attempts to prospectively evaluate how these important variables unfold across time to produce adaptationor disease. The candidate's long-term goal is to conduct multidisciplinary, programmatic research that evaluates causal relationships among stress, sleep, and health across the lifespan. Career development and research activities during the award period have been designed to address needs specific to this long-term goal. David J. Kupfer, M.D., who has conducted extensive research on psychobiological factors that affect sleep, will serve as the primary mentor on this MRSDA. Dr. Kupfer will ensure that the candidate develops the background and technical expertise necessary to conduct research that bridges the fields of behavioral medicine and sleep research. The candidate's short-and long-term career goals willbe further enhanced by directed readings and laboratory practica with pioneering investigators in the fields of behavioral medicine and sleep research, within and outside of the University of Pittsburgh.