The Psychoneuroimmunology of Insomnia: Response to a Vaccine Challenge

描述(由申请人提供)：尽管失眠的发病率非常高，但在整个生命周期内发病率不断上升，以及失眠的后果，失眠的病理生理学，特别是致病风险的途径，相对来说还没有得到研究。K奖的具体目标是参与一个培训和开发研究的计划，使申请者能够将心理神经免疫学(PNI)和失眠研究结合起来，并促进一个调查计划，试图描绘出失眠的两个持久过程(高觉醒和体内平衡失调)如何影响总体健康结果，特别是免疫功能。本申请中详细说明的发展计划旨在为申请者提供PNI、生物统计学、赠款、研究的道德行为以及如何与少数族裔社区打交道方面的培训。这项拟议的研究项目的具体目的是确定慢性失眠是否与对实验挑战的迟钝适应性免疫反应有关。这项研究对50名年龄在30-50岁的绝经前女性受试者(25名慢性失眠患者和25名睡眠良好者[GSS])进行了两组平行的ARM研究，以评估失眠是否与对乙肝疫苗挑战的迟钝抗体反应有关。每个受试者将接受已建立的三部分疫苗方案，每次接种后抽血以确定保护性抗体水平。需要检验的中心假设是，在第一次和第二次接种疫苗后，Pis的抗体效价(连续测量)和血清转换率(二分式测量)将低于GSS。除了对免疫能力的具体评估外，每天还将通过睡眠日记评估睡眠连续性；每周将通过症状清单评估健康状况。这些评估将在三个月内进行。拟议的职业培训计划和相关研究的价值在于将PI发展为具有沟通传统上独立的调查领域的技能和背景的个人，以及其以一种可能与健康结果直接相关的方式在操作上定义免疫能力的能力，以在被认为存在重大医疗发病率风险的临床人群中这样做，并且随着年龄的增长，这种情况变得越来越明显。

DESCRIPTION (provided by applicant): Despite its extraordinary prevalence, increasing incidence across the lifespan, and consequences, the pathophysiology of insomnia and, specifically, the pathways by which morbidity risk is conferred, have been relatively unstudied. The specific goal for this K-Award is to engage in a program of training and developing research that will allow the applicant to blend psychoneuroimmunology (PNI) and insomnia research, and to foster a program of investigation that seeks to delineate how two perpetuating processes of insomnia (hyperarousal and homeostatic dysregulation) affect health outcomes in general, and immune function in particular. The development program detailed in this application is structured to provide the applicant training in PNI, biostatistics, grantsmanship, the ethical conduct of research, and how one engages with minority communities. The specific aim for the proposed research project is to ascertain whether chronic insomnia is associated with a blunted adaptive immune response to an experimental challenge. This study uses a two-group, parallel arm study of 50 pre-menopausal female subjects aged 30-50 (25 with chronic insomnia [Pis] and 25 good sleepers [GSs]) to assess whether insomnia is associated with a blunted antibody response to a Hepatitis B vaccine challenge. Each subject will receive the established 3-part vaccine regimen, with blood draws to determine protective antibody levels following each administration. The central hypothesis to be tested is that Pis will have lower antibody titers (a continuous measure) and lower sero-conversion rates (a dichotomous measure) than GSs following the 1st and 2nd vaccinations. In addition to the specific assessment of immunocompetence, sleep continuity will be assessed daily with sleep diaries; health status will be assessed weekly with symptom checklists. These assessments will occur over a three month period. The value of the proposed career training program and the related research resides in the development of the PI as an individual with the skills and background to bridge traditionally separate domains of investigation, and its capacity to operationally define immunocompetence in a manner' that is likely to be directly related to health outcomes, to do so in a clinical population believed to be at risk for significant medical morbidity, and with a condition that becomes increasingly pronounced with aging.