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。那些社会经济地位低的人（SES）继续以20世纪70年代更典型的速度发展并死于CHD。大多数关于这些差异起源的研究都集中在生命的中期阶段，即CHD临床表现。虽然这项研究已经取得了丰硕成果，但将重点转移到早期生命阶段可能会产生有价值的见解。导致CHD的许多致病机制开始于儿童期，到青春期，越来越多的美国青年显示CHD的危险因素和临床前体征，其本身由SES模式。尽管有这些发现，相对较少的注意力已经针对早期CHD的差异。我们对它们为什么出现以及它们如何发展所知甚少。为了解决这些问题，我们提出了一个前瞻性的，多层次的研究，250名来自不同经济背景的青年。受试者将在八年级入组，并在十年级重新评估。从最近开发的概念框架的假设，该研究提出了三个问题，SES的免疫，神经和心理社会发展的差异，以及对早期冠心病风险的影响。首先，我们询问SES是否与免疫系统的成熟模式有关，重点是CHD的炎症过程。我们预计低SES青年表现出多层炎症表型，表现在基因组，细胞和系统水平的分析。其次，我们问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，从而引起增加CHD风险的行为倾向。使用高维结构成像和扩散张量成像，我们预计低SES与这些电路中的灰质和白质发育差异有关。反过来，这些差异预示着CHD相关的行为倾向，包括威胁警惕，社会动荡，自我调节不良和不健康的生活方式。最后，注意到一些低社会经济地位的青年有积极的健康结果，我们探讨的特点和经验，“弯曲”的规范人口曲线。我们预计，遇到积极社会影响（特别是榜样和高度母性温暖）的低社会经济地位青年将发展一系列个人资源（信任、情绪调节技能和自尊），帮助他们应对高中和低社会经济地位的挑战更广泛的生活。这些资源将使低社会经济地位的年轻人偏离他们预期的风险轨迹，导致与高社会经济地位年轻人相似的免疫和神经模式。

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.