The Psychoneuroimmunology of Insomnia: Response to a Vaccine Challenge

描述（由申请人提供）：尽管失眠症的患病率非常高，在整个生命周期内的发病率不断增加，其后果，但失眠症的病理生理学，特别是赋予发病风险的途径，相对而言尚未研究。该K奖的具体目标是参与培训和开发研究计划，使申请人能够将心理神经免疫学（PNI）和失眠研究相结合，并促进调查计划，旨在描述失眠的两个持续过程（过度觉醒和稳态失调）如何影响健康结果，特别是免疫功能。本申请中详细介绍的发展计划旨在为申请人提供PNI，生物统计学，生物学，研究道德行为以及如何与少数民族社区合作的培训。该研究项目的具体目标是确定慢性失眠是否与对实验挑战的适应性免疫反应迟钝有关。本研究采用两组、平行臂研究，纳入50例年龄在30-50岁的绝经前女性受试者（25例慢性失眠[Pis]和25例睡眠良好[GS]），以评估失眠是否与对B肝炎疫苗攻击的抗体应答减弱相关。每例受试者将接受既定的3部分疫苗方案，每次接种后抽血测定保护性抗体水平。待检验的中心假设是，在第1次和第2次疫苗接种后，与GS相比，PI的抗体滴度（连续测量）和血清转换率（二分测量）较低。除了免疫能力的具体评估外，还将通过睡眠日记每天评估睡眠连续性;每周使用症状检查表评估健康状况。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培养为具有技能和背景的个体，以弥合传统上独立的研究领域，以及其以可能与健康结局直接相关的方式操作性定义免疫能力的能力，以便在被认为有重大医学发病风险的临床人群中进行，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.