Childhood Origins of CHD Disparities: Neural & Immune Pathways

描述（由申请人提供）：近几十年来，美国冠心病（CHD）的发病率和死亡率显著下降。但这一趋势的强度因人口群体而异。那些低社会经济地位（SES）的人继续发展并死于冠心病，其发病率更像20世纪70年代。大多数关于这些差异起源的研究都集中在冠心病临床表现的中年阶段。虽然这项研究成果丰硕，但将焦点转移到生命早期阶段可能会产生有价值的见解。导致冠心病的许多致病机制始于儿童时期，到青春期，越来越多的美国年轻人表现出冠心病的危险因素和临床前症状，这些症状本身就是由SES引起的。尽管有这些发现，相对而言，很少有人关注早期冠心病的差异。我们对它们为什么出现以及它们如何发展知之甚少。为了解决这些问题，我们对250名来自不同经济背景的青年进行了前瞻性、多层次的研究。受试者将在八年级入学，并在十年级重新评估。根据最近发展的概念框架的假设，该研究提出了三个关于SES在免疫、神经和社会心理发育方面的差异以及对早期冠心病风险的影响的问题。首先，我们询问SES是否与免疫系统的成熟模式有关，重点关注冠心病背后的炎症过程。我们期望低社会经济地位的年轻人表现出多层次的炎症表型，这在基因组、细胞和系统水平的分析中表现出来。其次，我们询问SES是否与大脑皮质边缘和皮质纹状体回路的成熟模式有关，从而导致增加冠心病风险的行为倾向。利用高维结构成像和扩散张量成像，我们预计低SES与这些电路中灰质和白质发育的差异有关。反过来，这些差异应该预示着冠心病相关的行为倾向，包括威胁警惕、社会动荡、自我调节能力差和不健康的生活方式。最后，注意到一些低社会经济地位的年轻人有积极的健康结果，我们探索了“弯曲”规范人口曲线的特征和经历。我们期望社会经济地位较低的年轻人遇到积极的社会影响——特别是榜样和高度的母性温暖——将发展一套个人资源——信任、情绪调节技能和自尊——这将帮助他们更广泛地应对高中和社会经济地位较低的生活的挑战。这些资源将使经济地位低的青少年偏离预期的风险轨迹，导致免疫和神经模式与经济地位高的青少年相似。

DESCRIPTION (provided by applicant): In recent decades there has been a marked decline in morbidity and mortality from coronary heart disease (CHD) in the US. But the strength of this trend varies across demographic groups. Those of low socioeconomic status (SES) continue to develop, and die from, CHD at rates more typical of the 1970's. Most research on the origins of these disparities focuses on middle stages of the lifespan, when CHD manifests clinically. While this research has been fruitful, shifting the focus towards earlier life stages could yield valuabl insights. Many pathogenic mechanisms that give rise to CHD begin in childhood, and by adolescence increasing numbers of American youth display risk factors for and preclinical signs of CHD, which themselves pattern by SES. Despite these findings, relatively little attention has been directed towards early CHD disparities. We know little about why they emerge and how they unfold developmentally. To address these questions, we propose a prospective, multilevel study of 250 youth from economically diverse backgrounds. Subjects will be enrolled during eighth grade and reassessed in tenth grade. Drawing on hypotheses from a recently developed conceptual framework, the study poses three questions about SES disparities in immunologic, neural, and psychosocial development, and the implications for early CHD risk. First, we ask whether SES relates to maturation patterns in the immune system, with a focus on inflammatory processes that underlie CHD. We expect low-SES youth to display a multilayer inflammatory phenotype, which manifests at the genomic, cellular, and systemic levels of analyses. Second, we ask whether SES relates to maturation patterns in the brain's corticolimbic and corticostriatal circuitries, and thereby give rise to behavioral proclivities that heighten CHD risk. Using high-dimensional structural imaging and diffusion tensor imaging, we expect low SES to be associated with disparities in grey- and white-matter development in these circuitries. These disparities should, in turn, presage CHD-relevant behavioral proclivities, including threat vigilance, social turmoil, poor self-regulation, and unhealthy lifestyles. Finally, noting that som low-SES youth have positive health outcomes, we explore characteristics and experiences that "bend" the normative demographic curve. We expect that lower-SES youth who encounter positive social influences - specifically role models and high maternal warmth - will develop a suite of personal resources - trust, emotion regulation skills, and self-esteem - that help them navigate the challenges of high school and low-SES life more broadly. Those resources will shift low-SES youth off their expected risk trajectory, resulting in immune and neural patterns similar to higher-SES youth.