Sleep disturbance as a putative mechanism for reward system dysfunction

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DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award (K23) proposal includes a coordinated training plan and research project that will facilitate the Candidate's transition to independent investigator. It will provide the Candidate with the tools to become a leading expert on the basic human behavioral science behind the association of sleep disturbance and reward system function, and to develop an independent program of basic and clinical research on the interrelations of sleep disturbance, the reward system, and chronic pain in opioid-dependent patients. This topic area is important because opioid dependence is a growing public health problem, sleep disturbance and chronic pain are increasingly recognized as prevalent and problematic comorbidities, and understanding how sleep disturbance alters behavioral and affective measures of reward system function may enhance the limited treatment options for opioid-dependent patients with chronic pain. Long-term, the Candidate's program of research will employ a multimodal assessment strategy involving human biobehavioral laboratory experiments and longitudinal clinical research. The Candidate will need to become well-versed in the pathophysiological and neurobiological underpinnings of sleep and the reward system. Specific short-term training goals are: 1) Gain expertise in experimental sleep methods and assessment of sleep disturbance; 2) Gain training in the neurobiology and assessment of the reward system; 3) Gain training in research with opioid-dependent patients and 4) Gain training in the responsible conduct of research. The proposed short-term development activities will enable the Candidate to achieve his long-term goals by providing the necessary skill set to a) safely and effectively manipulate sleep; b) objectively measure sleep psychophysiology; c) objectively measure behavioral reward system function d) confidently interpret evidence of functional reward system changes from a biobehavioral perspective; e) recruit, retain, and responsibly execute research protocols with opioid dependent patients; and f) understand the psychopharmacological basis of opioid addiction and the clinical nuances of comorbid chronic pain. The proposed research project is divided into 2 studies. Study 1 will establish a basic behavioral model of sleep disturbance-induced reward system dysfunction in a within-person sleep deprivation experiment with healthy subjects. Study 2 will gather cross-sectional pilot data to determine if the association of sleep disturbance with reward system dysfunction is greater in opioid-dependent patients with versus without chronic pain. The coordinated training and research plans logically extend from the Candidate's prior work on emotion regulation in chronic musculoskeletal pain, and forge a novel research direction that addresses gaps in our current understanding of how sleep disturbance affects reward system function, and how that pathway contributes to chronic pain in patients with opioid dependence.