The Psychoneuroimmunology of Insomnia: Response to a Vaccine Challenge

描述（由申请人提供）：尽管失眠症非常普遍，在整个生命周期中发病率不断增加，后果也越来越严重，但失眠症的病理生理学，特别是产生发病风险的途径，相对来说还没有得到研究。该k奖的具体目标是参与一个培训和发展研究项目，使申请人能够将精神神经免疫学（PNI）和失眠研究结合起来，并培养一个调查项目，旨在描述失眠的两个持续过程（过度唤醒和体内平衡失调）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，资助，研究道德行为以及如何与少数民族社区交往方面的培训。该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适应性免疫反应迟钝有关。本研究采用两组平行对照研究，对50名年龄在30-50岁的绝经前女性受试者（25名患有慢性失眠[Pis]， 25名睡眠良好[GSs]）进行研究，以评估失眠是否与乙型肝炎疫苗攻击的钝化抗体反应相关。每位受试者将接受既定的三部分疫苗方案，每次给药后抽血以确定保护性抗体水平。待检验的中心假设是，在第一次和第二次接种疫苗后，Pis的抗体滴度（连续测量）和血清转换率（二分类测量）比GSs低。除了免疫能力的具体评估外，睡眠连续性将每天通过睡眠日记进行评估；每周将根据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人，以跨越传统上独立的调查领域，并具有在被认为有重大医疗发病率风险的临床人群中以可能与健康结果直接相关的方式定义免疫能力的能力。而且随着年龄的增长，这种情况越来越明显。

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.