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

描述(申请人提供)：除某些昆虫外，人类是地球上最具社会性的物种。与这一地位相适应的是，越来越明显的是，社会进程是人类健康的主要决定因素。无论是被概念为社会融合还是社会支持，积极的社会联系(PSC)已经在数百项研究中被证明可以预防疾病的发展，一旦疾病确定，就减少发病率，并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)--无论是以孤独、社会孤立还是人际冲突来衡量--都预示着疾病的发展以及与疾病相关的发病率和死亡率的增加。目前的提议旨在确定PCS/NSP与心理社会应激相互作用的行为和生理机制，以提高在疾病背景下的复原力。当前项目的一个中心创新是，对社会过程和应激反应的评估将不依赖于第一人称报告、对多种情况的概括或回溯性报告。相反，PSC/NSP和应激反应将被客观地评估--也就是从第三人称的角度--实时和在特定情况下。同样，我们没有依赖变幻莫测和复杂的自然疾病过程来提供与健康相关的行为结果，而是通过使用干扰素(干扰素)-α治疗来模拟炎症(所有疾病状态的核心要素)。干扰素-α提供了一种标准化的慢性细胞因子暴露方案，已知会在高比例的个体中产生严重的行为障碍，包括抑郁、疲劳和疾病。为了客观地评估社交过程，目前的项目将使用电子激活记录器(EAR)，它定期且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这款设备。在跟踪每时每刻的环境声音时，它会产生自然展开时它们的行为和交互的声学记录。为了客观地评估对心理社会压力的行为和生理反应，目前的项目将使用Trier社会压力测试(TSST)，这是一种已知可以可靠地激活行为、神经内分泌和炎症反应的标准化实验室应激源。这些新的方法和模型系统将被用来检验以下假设：(A)先前存在的从属行为和亲社会行为将促进慢性炎症背景下的韧性，以及(B)相反，慢性炎症将通过对应激反应、神经内分泌功能和睡眠的影响而减少从属行为和亲社会行为。最后，它将探索(C)应激生理学的潜在中介作用。为了验证这些假设，120名慢性丙型肝炎病毒感染者将随机接受聚乙二醇化干扰素-α联合利巴韦林治疗或将治疗推迟8周。在随机化之前和8周后，所有受试者将在他们的家庭环境中用耳朵进行评估，并将在埃默里大学的亚特兰大临床和翻译科学研究所临床互动网络网站进行TSST、14小时昼夜神经内分泌和免疫测量以及过夜睡眠多导睡眠图。

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.