Predisposition Model of Insomnia

描述（由申请人提供）：候选人的计划/培训：候选人的目标是在睡眠医学领域以患者为导向的临床研究中的职业生涯，重点是失眠和伴随的精神疾病。培训计划将包括在当地两所大学举办的11个课程，以及由失眠症病理生理学和治疗、脑磁图、内分泌学和创伤后应激障碍专家提供的正式教学和实验室培训。培训将分单元进行，每个单元就与拟议研究计划有关的专题和候选人成为独立调查员的长期职业目标提供具体指导和咨询。 环境：亨利福特睡眠中心是一个完善的研究设施，将是一个理想的培训地点，这个奖项。导师制，部门内和跨部门的强大合作，以及一个专门的研究承诺的机构联合收割机相结合，提供一个非常适合年轻科学家的职业发展的环境。 研究：据估计，慢性失眠的患病率在普通人群中占10- 15%。抑郁症与整个生命周期中抑郁症的发病率增加2至5倍有关，并对生活质量产生重大负面影响。原发性失眠的模型一般概念化的病理生理学的背景下，这种疾病的沉淀事件叠加在诱发和随后的维持因素。然而，到目前为止，尚未研究使个体易患急性睡眠障碍的因素以及这种易患性对慢性失眠发展的意义。我们的原发性失眠模型提出，过度觉醒（标记：情绪反应，β频率EEG和HPA轴激活响应“挑战”）与急性睡眠中断的脆弱性相关。我们认为，过度觉醒及其相关的急性睡眠中断的脆弱性代表了慢性原发性失眠的后续发展的倾向，通过持续的睡眠中断后，去除沉淀。在这个模型的框架内，我们提出了两个实验来识别和表征失眠的易感性，其中1）一个没有失眠但具有与原发性失眠患者相似的情绪反应（NER）标记的高觉醒的个体子集，具有由在实验室的第一个晚上和夜间咖啡因给药引起的睡眠障碍的一般脆弱性; 2）然而，与患有慢性失眠症的个体不同，在非挑战性夜晚，这些高NER个体显示正常睡眠; 3）高NER个体具有与慢性失眠症患者相似的增加的生理唤醒; 4）最后，当睡眠中断的可能性仍然存在时，在去除持续的睡眠中断诱发剂之后，易感个体具有延长的睡眠障碍。

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.