Personality, Stress, and HSV-1 Infection: A Twin Study

描述(由申请人提供)：大量和不断增长的心理神经免疫学研究表明，心理压力是免疫系统功能的重要调节因素。然而，最近的研究表明，导致免疫系统变化的不是压力源本身的存在，而是对压力源的评价和反应的个体差异。这些个体差异很可能是神经质和尽职尽责等明显个性特征的作用--这些特征可遗传，与生活事件和健康结果密切相关。单纯疱疹病毒(HSV)感染是精神神经免疫学研究的主要焦点，因为HSV感染在人类中普遍存在，临床和病毒学严重程度的决定因素尚不清楚。单纯疱疹病毒精神神经免疫学研究的主要结果指标是典型的临床症状或抗体滴度。但这些措施并不一定反映了脱皮的增加，从而增加了HSV传播的风险。我们开发了一种客观的方法来量化粘膜表面HSV感染的病毒学严重性，该方法比测量症状更敏感，比测量抗体滴度更特异。在这个项目中，我们将把人格和压力相关心理变量的评估与单纯疱疹病毒研究中最敏感和临床相关的结果测量结合起来，进行一项双胞胎研究，使我们能够控制研究参与者的遗传学和病毒基因的变异性。因此，我们将比较与疾病一致的同性同卵双胞胎(MZ)和异卵双胞胎(DZ)的HSV脱落率，同时评估日常压力评估和每周特定压力源和相关评估的报告，以及包括神经质、责任心和乐观在内的心理特征。使用这种双胞胎设计将使我们能够评估压力和HSV传播的生物学和心理社会方面，同时控制遗传变异性和常见的家族暴露和经历。具体目的是：1)评估压力源和压力评估对HSV脱落率的影响；2)确定人格测量与HSV脱落率之间的关系；3)评估压力源、压力评估和人格测量对HSV脱落率的联合影响。公共卫生相关性：越来越多的研究将人格特征、压力和压力归因与已经呈单纯疱疹病毒阳性的人中的1型单纯疱疹病毒(HSV-1)爆发联系起来。然而，关于个性和压力是如何影响免疫系统的，仍有很多有待发现。在这项研究中，我们将研究双胞胎的个性、压力和HSV-1之间的关系，以更好地阐明人、病毒和环境是如何相互作用的。

DESCRIPTION (provided by applicant): A large and growing body of psychoneuroimmunology research demonstrates that psychological stress is an important moderator of immune system functioning. Recent studies suggest, however, that it is not the presence of a stressor per se but rather individual difference in appraisals of, and responses to, the stressor that leads to changes in the immune system. Those individual differences are likely a function of distinct personality traits such as neuroticism and conscientiousness - heritable characteristics that are strongly related to exposure to life events as well as health outcomes. Herpes simplex virus (HSV) infection is a principle focus of psychoneuroimmunology research because HSV infections are ubiquitous in humans and the determinants of the clinical and virological severity are unknown. The primary outcome measures in psychoneuroimmunology studies of HSV are typically clinical symptoms or antibody titers. But these measures do not necessarily reflect increases in shedding and thus increased risk of HSV transmission. We have developed an objective method to quantify the virologic severity of HSV infections on mucosal surfaces that is more sensitive than measuring symptoms and more specific than measuring antibody titers. In this project we will combine assessment of personality and stress-related psychological variables with the most sensitive and clinically relevant outcome measure in HSV research for a twin study that will allow us to control for the genetics of both the study participants and variability in virus genotype. We will thus compare HSV shedding rates for disease-concordant same-sex monozygotic (MZ) and dizygotic (DZ) twin pairs while assessing daily stress appraisals and weekly reports of specific stressors and related appraisals, along with psychological traits including neuroticism, conscientiousness, and optimism. Using this twin design will allow us to assess biological and psychosocial aspects of stress and HSV shedding, while controlling for genetic variability and common familial exposures and experiences. The Specific Aims are to 1) assess the influence of stressors and stress appraisals on HSV shedding rates; 2) determine the relationship between measures of personality and HSV shedding rates; and 3) assess the joint influence of stressors, stress appraisals, and measures of personality on HSV shedding rates. PUBLIC HEALTH RELEVANCE: There is a growing body of research that links personality traits, stress, and stress attributions to outbreaks of herpes simplex virus type 1 (HSV-1) among those who are already HSV-positive. However, a great deal remains to be discovered about how personality and stress affect the immune system. In this study, we will examine the relationships among personality, stress, and HSV-1 in twins to better elucidate how the person, the virus, and the environment interact.