Clinical translation of phenotypes of shift work disorder

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PROJECT SUMMARY/ABSTRACT Shift work disorder (SWD) is a significant threat to public health and safety; over 6 million shift workers in the United States experience the debilitating symptoms of excessive sleepiness and insomnia, and suffer functional impairments that increases the risk of catastrophic industrial accidents. However, patients with SWD are often inadequately treated because the pathophysiology is not well-characterized, and current diagnostic assessments do not identify specific treatment targets. Consequently, clinicians are unable to deliver precise interventions that target the underlying causes of SWD. The proposed project in this career development award will address these gaps by taking the initial steps of translating two phenotypes of SWD for clinical use. Previous research has indicated that SWD can arise from two independent pathways that can be categorized as pathophysiological phenotypes. The first is the circadian misalignment phenotype, characterized by poor adjustment of the biological clock to the nocturnal work schedule. The second is the sleep reactivity phenotype, characterized by a trait vulnerability to sleep disturbance triggered by environmental stressors. Both phenotypes lead to symptoms of sleepiness and insomnia in SWD, and is not currently distinguished in the clinic; however, the requisite treatments for each pathophysiological phenotype are entirely different. As such, the appropriate intervention of SWD requires that these phenotypes be adequately characterized and identified in the clinic. The proposed aims will complete the requisite foundational research to launch the translation of these phenotypes of SWD for clinical use. The first research aim will examine the stability of each phenotype in shift workers to characterize them as either state or trait phenotypes, which will impact both assessments of interventions. The second research aim will identify the specific clinical attributes that can be used to index the phenotypes in a brief, accurate, and cost-effective assessment tool. Finally, the third research aim will identify differences in cognitive and performance deficits between the two phenotypes so that accidents and injuries can be preempted with targeted interventions.To successfully complete the research aims, and to support my long term goal of conducting translational research to improve the health and productivity of shift workers, this career development award will provide further training in the following areas: (1) development of clinical screening tools, (2) advanced methodologies in clinical and translation research, (3) feasibility of “real-world” behavioral interventions for shift work disorder, and (4) advanced field measurement of circadian phase. In combination, the training activities outlined in this career development award will provide the necessary expertise for a sustained career in translational research and circadian medicine.