Clinical translation of phenotypes of shift work disorder

项目摘要/摘要 轮班工作紊乱(SWD)是对公众健康和安全的重大威胁；全国有600多万轮班工人 美国经历了过度困倦和失眠的衰弱症状，并遭受 增加灾难性工业事故风险的功能障碍。然而，社署的病人 由于病理生理学没有得到很好的描述，目前的诊断往往没有得到充分的治疗 评估没有确定具体的治疗目标。因此，临床医生无法准确地提供 针对社署根本原因的干预措施。这一职业发展中的拟议项目 AWARD将通过采取初步步骤将两种表型的SWD翻译为临床使用，以解决这些差距。 先前的研究表明，社会功能障碍可以由两条独立的途径产生，这两条途径可以被归类 作为病理生理表型。第一种是昼夜节律失调表型，其特征是 调整生物钟以适应夜间工作时间表。第二个是睡眠反应性 表型，特征是易受环境应激源引发的睡眠障碍的影响。 在社署，这两种表型都会导致嗜睡和失眠的症状，目前在 然而，针对每一种病理生理表型的必要治疗是完全不同的。AS 因此，社署的适当干预需要这些表型得到充分的表征和 在诊所确认了身份。拟议的目标将完成必要的基础研究，以启动 翻译这些SWD表型以供临床使用。第一个研究目标将检查每种方法的稳定性 轮班工人的表型，将他们描述为状态表型或特征表型，这将影响两者 对干预措施的评估。第二个研究目标将确定特定的临床属性， 用于在简短、准确和经济高效的评估工具中为表型编制索引。最后，第三个 研究目的将确定两种表型在认知和表现缺陷上的差异，以便 事故和伤害可以通过有针对性的干预来预防。为了成功地完成研究 目标，并支持我的长期目标，进行翻译研究，以改善健康和 为了提高轮班工人的生产率，该职业发展奖将在以下方面提供进一步的培训： (1)临床筛查工具的开发；(2)临床和翻译研究的先进方法；(3) 对倒班工作障碍进行“真实世界”行为干预的可行性，以及(4)先进的现场测量 昼夜节律阶段的。综合考虑，本职业发展奖中概述的培训活动将提供 在翻译研究和昼夜节律医学领域持续发展所需的专业知识。

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.