An Affective Intervention to Reverse the Biological Residue of Low Childhood SES

 在低社会经济（SES）家庭中长大的个人被发现承担20%-40%的昂贵的慢性病和传染病以及全因死亡率的风险增加，即使在考虑成年SES之后。阐明这些健康风险的生物学机制，最近的研究已经确定，生命早期经历的严重和慢性压力可以在免疫系统中嵌入长达数十年的“生物残留物”，如白细胞基础基因表达谱，白细胞端粒长度和C反应蛋白指数的慢性炎症水平所反映的。这些生物风险因素进一步加剧了行为倾向，即冲动（延迟折扣指数）和不信任，这也更可能在低社会经济地位家庭中长大。拟议研究的总体目标是调查这种已确定的生物残留物是否以及如何在中年时逆转。一种创新的螺旋式上升的生活方式改变理论将温暖和移情的情绪状态定位为释放身体内在可塑性的关键途径，以扭转根深蒂固的生物风险因素。PI的团队已经确定了一种情感干预--慈爱冥想（LKM）的古老实践--它在健康的中年人中产生有益健康的生物学效应。本研究的创新之处在于，在一个健康状况不佳的中年人样本中测试这种情感干预，因为他们的童年社会经济地位低，加上现在的致病行为倾向（即，冲动和不信任）。一项双盲安慰剂对照随机对照试验（RCT）旨在提供原则证明，即早期确定的生物学风险因素是可变的，而不是永久性的。它有三个具体目标：（1）测试LKM是否通过其对积极情绪的影响，可以逆转儿童低SES的生物残留，如（a）白细胞基础基因表达（促炎基因的上调和抗病毒和抗体基因的下调），（B）白细胞端粒长度，和（c）C-反应蛋白;（2）在该高危样本中确定LKM的假设益处的合理的行为和生物调节因子，候选调节因子为（a）冥想花费的时间和（B）代谢特征;以及（3）在这个处于风险中的样本中，确定LKM诱导的积极情绪的假设生物学益处的合理生物学、行为学和心理学介质，候选介质是（a）心脏迷走神经张力、（B）延迟贴现和（c）不信任的改善。这项研究旨在确定以证据为基础的干预措施，以大幅减少不成比例地影响低SES家庭的美国人的疾病负担。

 DESCRIPTION (provided by applicant): Individuals raised in low socioeconomic (SES) households have been found to bear 20%-40% increased risk of costly chronic and infectious diseases and all-cause mortality, even after accounting for adulthood SES. Illuminating the biological mechanisms of these health risks, recent research has determined that severe and chronic stress endured early in life can embed a decades-long "biological residue" within the immune system, as reflected in leukocyte basal gene expression profiles, leukocyte telomere length, and levels of chronic inflammation indexed by C-reactive protein. These biological risk factors are further exacerbated by behavioral proclivities, namely, impulsivity (indexed by delay discounting) and mistrust, which are also more probable among those reared in low SES households. The overarching goal of the proposed research is to investigate whether and how this identified biological residue can be reversed in midlife. An innovative upward spiral theory o lifestyle change positions warm and empathic emotional states as key pathways to unlocking the body's inherent plasticity to reverse entrenched biological risk factors. The PI's team has identified an affective intervention - the ancient practice of loving-kindness meditation (LKM) - that produces salubrious biological effects in healthy midlife adults. The innovation of the present study lies in testing this affective intervention in a sample of midlife adults on poor health trajectories by virtue of having low childhood SES plus present-day pathogenic behavioral tendencies (i.e., impulsivity and mistrust). A dual-blind placebo-controlled randomized controlled trial (RCT) is designed to provide proof of principle that early-established biological risks factors are mutable, not permanent. It targets three Specific Aims: (1) To test whether LKM, through its effects on positive emotions, can reverse the biological residue of low childhood SES as reflected in (a) leukocyte basal gene expression (up-regulation of pro-inflammatory genes and down-regulation of antiviral and antibody genes), (b) leukocyte telomere length, and (c) C-reactive protein; (2) to identify plausible behavioral and biological moderators of the hypothesized benefits of LKM in this at-risk sample, with candidate moderators being (a) time spent meditating and (b) metabolic profile; and (3) to identify plausible biological, behavioral, and psychological mediators of the hypothesized biological benefits of LKM-induced positive emotions in this at-risk sample, with candidate mediators being improvements in (a) cardiac vagal tone, (b) delay discounting, and (c) mistrust. This research stands to identify evidence-based interventions to drastically reduce the disease burden that disproportionately affects Americans raised in low SES households.