Predisposition Model of Insomnia

Henry Ford Health System, Detroit MI

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Abstract

DESCRIPTION (provided by applicant): Candidate's Plans/Training: The candidate's goal is for a career in patient-oriented clinical research in the field of sleep medicine with a focus on insomnia and concomitant psychiatric disease. The training plan will include 11 courses at two local Universities and formal didactic and laboratory training from experts on insomnia pathophysiology and treatment, magnetoencephalography, endocrinology, and post-traumatic stress disorder. Training will be organized in modules each providing specific instruction and consultation regarding topics related to the proposed research plan and the candidate's long-term career goal of becoming an independent investigator. Environment: Henry Ford Sleep Center is a well-established research facility and would be an ideal training site for this award. Proven mentorship, strong within and across departmental collaboration, and an institution with a dedicated research commitment combine to provide a setting well suited for the career development of a young scientist. Research: The prevalence of chronic insomnia has been estimated to be between 10-15 percent of the general population. Insomnia is associated with a two to five-fold greater incidence of depressive disorders across the lifespan, and a significant negative impact on quality of life. Models of primary insomnia generally conceptualize the pathophysiology of this disorder in the context of a precipitating event superimposed upon predisposing and subsequent maintaining factors. However, to date, factors that predispose individuals to acute sleep disturbance and the significance of that predisposition for the development of chronic insomnia has not been investigated. Our model of primary insomnia proposes that hyperarousability (markers: emotional reactivity, beta frequency EEG, and HPA axis activation in response to a "challenge") is associated with vulnerability to acute sleep disruption. It is our view that hyperarousability and its associated vulnerability to acute sleep disruption represents a predisposition to the subsequent development of chronic primary insomnia by sustaining sleep disruption following the removal of a precipitant. Within the framework of this model we propose two experiments to identify and characterize a predisposition to insomnia in which 1) a subset of individuals without insomnia but who have elevated arousal as marked by emotional reactivity (NER) similar to that seen in patients with primary insomnia, have a general vulnerability to sleep disturbance induced by a first night in the laboratory and nocturnal caffeine administration; 2) however, unlike individuals with chronic insomnia, on non-challenge nights, these high NER individuals show normal sleep; 3) high NER individuals have increased physiological arousal similar to chronic insomniacs; 4) finally, predisposed individuals have protracted sleep disturbance following the removal of a sustained sleep disrupting precipitant when the possibility of sleep disruption remains.