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

炎症、压力和社会行为：使用生态评估和模型

• 批准号: 8473381
• 负责人: Charles Raison
• 金额: $ 54.63万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8473381
• 关键词: Inflammation; Stress; Social; Behavior; Using

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.

描述（由申请人提供）：不包括某些昆虫，人类是地球上至高无上的社会物种。符合这种地位，越来越明显的是，社会过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，在数百项研究中都展示了积极的社会联系（PSC），以防止疾病发展，以减少疾病一旦建立疾病并从一系列自然原因中降低死亡率。相反，负面的社会过程（NSP） - 是否以孤独感，社会孤立或人际冲突预测的疾病发展以及与疾病相关的发病率和死亡率的增加。当前的建议旨在确定PC/NSP与社会心理压力相互作用以在疾病背景下促进韧性的行为和生理机制，当前项目的核心创新是对社会过程和压力反应的评估将不依赖于第一人称报告，关于多种情况或回顾性报告的概括。相反，PSC/NSP和应力反应性将被客观地评估 - 从第三人称的实时角度和特定情况下。同样，我们不是通过使用干扰素（IFN）-Alpha的治疗来对炎症（所有疾病状态的核心元素）进行建模，而不是依靠自然疾病过程的变化和复杂性来提供与健康相关的行为结果，这提供慢性细胞因子暴露的标准化方案已知会产生严重的行为障碍，包括抑郁症，疲劳和疾病，在很大比例的个体中。为了客观地评估社会过程，当前的项目将采用电子激活的录音机（EAR），该录音机（EAR）定期且毫不客气地记录了人们瞬间环境中环境声音的片段。参与者在生活时佩戴该设备。在跟踪时刻到时刻的环境声音时，它会在自然展开时产生其行为和相互作用的声学日志。为了客观地评估对心理压力的行为和生理反应，当前项目将采用Trier社会压力测试（TSST），这是一种已知可靠地激活行为，神经内分泌和炎症反应的标准实验室压力源。这些新颖的方法和模型系统将用于检验（a）（a）先前存在的亲属和亲社会行为的假设，将在慢性炎症的背景下促进弹性，并且（b） - 偶然炎症将通过关联性和社会性行为通过对压力反应性，神经内分泌功能和睡眠的影响。最后，它将探索（c）压力生理的潜在介导作用。为了检验这些假设，将随机分配120名患有慢性丙型肝炎病毒感染的受试者，以接受类化的IFN-Alpha加上Ribavirin或将治疗推迟8周。在随机分组之前和8周后，所有受试者都将在其家庭环境中用耳朵进行评估，并将在亚特兰大临床和翻译科学研究所网站上，将经历TSST，14小时的昼夜神经内分泌和免疫测量以及在亚特兰大临床和翻译科学研究所网站上的夜间睡眠多多个。