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

 描述(由申请人提供)：在低社会经济(SES)家庭长大的个人被发现，即使在计入成年社会经济家庭(SES)后，其患昂贵的慢性病和传染病以及各种原因死亡的风险增加了20%-40%。为了阐明这些健康风险的生物学机制，最近的研究确定，在生命早期承受的严重和长期应激可在免疫系统中嵌入长达数十年的“生物残留物”，这反映在白细胞基础基因表达谱、白细胞端粒长度和C反应蛋白指示的慢性炎症水平上。这些生物风险因素因行为倾向而进一步加剧，即冲动(以延迟折扣为指标)和不信任，这在那些在低社会经济地位家庭长大的人中也更有可能。这项拟议研究的首要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。一种关于生活方式改变的创新螺旋上升理论将温暖和同理心的情绪状态定位为释放身体固有可塑性的关键途径，以逆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--古老的慈爱冥想(LKM)--在健康的中年成年人中产生健康的生物效应。本研究的创新之处在于，在一个中年成年人的样本中测试了这种情感干预，这些人的健康轨迹很差，因为他们童年时的SES较低，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)旨在提供原则证据，证明早期建立的生物风险因素是可变的，而不是永久性的。它针对三个具体目标：(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，反映在(A)白细胞基础基因表达(促进炎症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，以及(C)C-反应蛋白；(2)在这个高危样本中，确定LKM假想益处的可信的行为和生物调节因素，候选调节因素是(A)花在冥想上的时间和(B)代谢特征；以及(3)在这一高危样本中，确定LKM诱导的积极情绪假想的生物学益处的可信的生物学、行为和心理中介，候选中介是(A)心脏迷走神经张力的改善，(B)延迟折扣，和(C)不信任。这项研究旨在确定以证据为基础的干预措施，以大幅减少疾病负担，这些疾病负担对在低社会经济地位家庭长大的美国人造成了不成比例的影响。

 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.