Predisposition Model of Insomnia

描述(由申请人提供)：候选人的计划/培训：候选人的目标是从事睡眠医学领域以患者为中心的临床研究，重点是失眠和伴随的精神疾病。培训计划将包括两所当地大学的11门课程，以及失眠病理生理学和治疗、脑磁图、内分泌学和创伤后应激障碍专家的正式教学和实验室培训。将以单元形式组织培训，每个单元提供与拟议研究计划和候选人成为独立调查员的长期职业目标有关的专题的具体指导和咨询。 环境：亨利·福特睡眠中心是一家久负盛名的研究机构，将是该奖项的理想培训地点。经过验证的导师制度、部门内和部门间强有力的协作以及致力于研究的机构相结合，为年轻科学家的职业发展提供了非常合适的环境。 研究：据估计，慢性失眠的患病率在总人口的10%-15%之间。失眠与一生中抑郁障碍的发病率增加两到五倍有关，并对生活质量产生重大负面影响。原发性失眠的模型通常将这种疾病的病理生理学概念化，其背景是叠加在诱因和随后的维持因素上的诱发事件。然而，到目前为止，使个人易患急性睡眠障碍的因素以及这种易感性对慢性失眠发展的意义尚未被调查。我们的原发失眠模型认为，高度唤醒能力(标志物：情绪反应性、β频率脑电波和HPA轴对“挑战”的反应)与急性睡眠中断的易感性有关。我们认为，过度觉醒及其对急性睡眠干扰的易感性代表了在移除沉淀物后持续睡眠中断，从而易于随后发展为慢性原发失眠。在这个模型的框架内，我们提出了两个实验来识别和描述失眠的易感性，其中1)没有失眠但有类似于原发性失眠患者的情绪反应性(NER)的觉醒升高的个体的子集，对第一晚在实验室和夜间服用咖啡因引起的睡眠干扰具有一般的易感性；2)然而，不同于慢性失眠的个体，在非挑战的夜晚，这些高水平个体表现出正常的睡眠；3)高水平个体的生理唤醒增加，类似于慢性失眠；4)最后，当睡眠中断的可能性仍然存在时，易患上睡眠障碍的人在移除持续的睡眠干扰沉淀剂后会长期睡眠障碍。

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.