Inflammation, Stress, and Social Behavior: Using Ecological Assessments and Model

描述（由申请人提供）：除了某些昆虫，人类是地球上最具社会性的物种。与这一地位相适应，人们越来越清楚地认识到，社会进程是人类健康的主要决定因素。无论是被概念化为社会融合还是社会支持，数百项研究都表明，积极的社会联系可以防止疾病发展，一旦疾病确立，可以减少发病率，并可以减少一系列自然原因造成的死亡率。相反，消极的社会过程（NSP）-无论是衡量孤独，社会孤立或人际冲突-预测疾病的发展和伴随的疾病相关的发病率和死亡率的增加。目前的建议已被设计为确定行为和生理机制，通过PCS/NSP与心理社会压力相互作用，以促进在疾病的背景下的恢复力，当前项目的一个核心创新是，社会过程和压力反应的评估将不依赖于第一人称报告，在许多情况下的概括或回顾性报告。相反，将在真实的时间和特定情况下客观地评估PSC/NSP和压力反应性（即从第三人称的角度）。同样，我们不是依靠自然疾病过程的变幻莫测和复杂性来提供与健康相关的行为结果，而是模拟炎症通过使用干扰素（IFN）-α的治疗来治疗癌症（所有疾病状态的中心要素），所述干扰素（IFN）-α提供了已知在高百分比的个体中产生严重的行为障碍（包括抑郁、疲劳和疾病）的慢性细胞因子暴露的标准化方案。为了客观地评估社会过程，目前的项目将采用电子激活录音机（Electronically Activated Recorder，简称EAR），它定期地、不引人注目地记录人们瞬间环境中的环境声音片段。参与者在生活中佩戴该设备。在跟踪每时每刻的环境声音时，它会在它们自然展开时产生它们的行为和相互作用的声学日志。为了客观地评估对心理社会压力的行为和生理反应，目前的项目将采用特里尔社会压力测试（TSST），这是一种标准化的实验室压力源，已知可以可靠地激活行为，神经内分泌和炎症反应。这些新的方法和模型系统将被用来测试假设，即（a）预先存在的亲和和亲社会行为将促进在慢性炎症的背景下的弹性和（B）-反向慢性炎症将减少亲和和亲社会行为通过对应激反应，神经内分泌功能和睡眠的影响。最后，它将探讨（c）压力生理学的潜在中介作用。为了检验这些假设，120例慢性丙型肝炎病毒感染的受试者将随机接受聚乙二醇化IFN-α加利巴韦林治疗或推迟治疗8周。在随机化之前和8周后，所有受试者将在其家庭环境中接受TSST评估，并将在埃默里大学的亚特兰大临床和转化科学研究所临床相互作用网络站点接受TSST、14小时昼夜神经内分泌和免疫测量以及夜间睡眠多导睡眠描记术。

DESCRIPTION (provided by applicant): Excluding certain insects, humans are the Earth's supremely social species. Befitting this status, it is increasingly clear that social processes are a prime determinant of human health. Whether conceptualized as social integration or social support, positive social connectivity (PSC) has been shown in hundreds of studies to protect against illness development, to reduce morbidity once illness is established and to reduce mortality from an array of natural causes. Conversely, negative social processes (NSP)-whether measured as loneliness, social isolation or interpersonal conflict-predict disease development and concomitant increases in disease-related morbidity and mortality. The current proposal has been designed to identify behavioral and physiological mechanisms through which PCS/NSP interact with psychosocial stress to promote resilience in the context of illness, A central innovation of the current project is that assessments of social processes and stress reactivity will not rely on first person report, on generalizations across a number of circumstances or on retrospective reporting. Rather, PSC/NSP and stress reactivity will be assessed objectively-that is from a third person perspective-in real time and in specific situations. Similarly, rather than relying on the vagaries and complexities of natural disease processes to supply health-relevant behavioral outcomes, we model inflammation (a central element of all disease states) through the use of treatment with interferon (IFN)-alpha, which provides a standardized regimen of chronic cytokine exposure known to produce profound behavioral disturbances, including depression, fatigue and sickness, in a high percentage of individuals. To objectively assess social processes, the current project will employ the Electronically Activated Recorder (EAR), which periodically and unobtrusively records snippets of ambient sounds in people's momentary environments. Participants wear the device while going about their lives. In tracking moment-to-moment ambient sounds, it yields acoustic logs of their behaviors and interactions as they naturally unfold. To objectively assess behavioral and physiological responses to psychosocial stress the current project will employ the Trier Social Stress Test (TSST), a standardized laboratory stressor known to reliably activate behavioral, neuroendocrine and inflammatory responses. These novel methodologies and model systems will be employed to test the hypotheses that (a) pre-existing affiliative and prosocial behavior will promote resilience in the context of chronic inflammation and that (b) -conversely-chronic inflammation will reduce affiliative and prosocial behavior via effects on stress reactivity, neuroendocrine function and sleep. Finally, it will explore (c) the potential mediating role of stress physiology. To test these hypotheses, 120 subjects with chronic hepatitis C virus infection will be randomized to receive treatment with pegylated IFN-alpha plus ribavirin or to postpone treatment for 8 weeks. Prior to randomization and 8 weeks later all subjects will be evaluated with the EAR in their home environments and will undergo TSST, 14 hour diurnal neuroendocrine and immune measurement and overnight sleep polysomnography in the Atlanta Clinical and Translational Science Institute Clinical Interactions Network site at Emory University.