Childhood Origins of CHD Disparities: Neural & Immune Pathways

先天性心脏病差异的童年根源：神经性

• 批准号: 9181446
• 负责人: Gregory Evan Miller
• 金额: $ 76.97万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9181446
• 关键词: Address; Adolescence; Adult; American; Amygdaloid structure; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Attention; Behavior; Behavioral; Biological; Brain; Buffers; Characteristics; Child Rearing; Childhood; Chronic; Clinical; Coronary heart disease; Corpus striatum structure; Data; Development; Diffusion Magnetic Resonance Imaging; Disadvantaged; Disease; Economics; Emotional; Enrollment; Evolution; Face; Family; Genomics; Gray unit of radiation dose; Health; Heart Diseases; Hippocampus (Brain); Household; Image; Immune; Immune system; Immunologics; Incidence; Inflammation; Inflammatory; Inflammatory Response; Informal Social Control; Intervention; Interview; Life; Life Experience; Longevity; Magnetic Resonance Imaging; Mediation; Metabolic; Metabolic syndrome; Morbidity - disease rate; Nucleus Accumbens; Outcome; Pathogenicity; Pathway interactions; Pattern; Phenotype; Poverty; Prefrontal Cortex; Prevention; Process; Repression; Research; Resources; Risk; Risk Factors; Self-control as a personality trait; Series; Shapes; Signal Transduction; Sleep; Smoking; Socioeconomic Status; Statistical Models; Structure; Suggestion; System; Teenagers; Thick; Transcriptional Regulation; Trust; Violence; Youth; cardiovascular health; cytokine; deprivation; dimensional analysis; disorder risk; eighth grade; emotion regulation; experience; follow-up; gray matter; heart disease risk; high dimensionality; high school; immune function; insight; low socioeconomic status; microbial; mortality; neural patterning; neurodevelopment; optimism; peer; pre-clinical; prospective; protein biomarkers; psychosocial development; public health relevance; relating to nervous system; response; role model; self esteem; skills; social; socioeconomics; stressor; tenth grade; trend; unhealthy lifestyle; vigilance; white matter

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.

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着下降。但这种趋势的强度因人口群体而异。那些社会经济地位 (SES) 较低的人继续罹患冠心病并以 20 世纪 70 年代较为典型的速度死于冠心病。大多数关于这些差异起源的研究都集中在生命中期，即冠心病临床表现的阶段。虽然这项研究取得了丰硕的成果，但将焦点转向生命早期阶段可能会产生有价值的见解。引起冠心病的许多致病机制始于儿童时期，到了青春期，越来越多的美国青少年表现出冠心病的危险因素和临床前症状，而这些症状本身就是由 SES 表征的。尽管有这些发现，但人们对早期先心病差异的关注相对较少。我们对它们为何出现以及它们如何发展发展知之甚少。为了解决这些问题，我们提议对 250 名来自不同经济背景的年轻人进行前瞻性、多层次的研究。科目将在八年级期间注册，并在十年级时重新评估。该研究利用最近制定的概念框架中的假设，提出了三个关于社会经济地位在免疫、神经和社会心理发展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 CHD 背后的炎症过程。我们预计低社会经济地位的青少年会表现出多层炎症表型，这在基因组、细胞和系统分析水平上表现出来。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，从而引起增加冠心病风险的行为倾向。使用高维结构成像和扩散张量成像，我们预计低 SES 与这些电路中灰质和白质发育的差异有关。这些差异反过来应该预示着与先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，我们注意到一些社会经济地位低的年轻人有积极的健康结果，因此我们探讨了“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青少年在遇到积极的社会影响（特别是榜样和母亲般的温暖）时，能够发展出一套个人资源——信任、情绪调节技能和自尊，帮助他们更广泛地应对高中和低社会经济地位生活的挑战。这些资源将使社会经济地位低的青少年偏离预期的风险轨迹，从而导致与社会经济地位高的青少年相似的免疫和神经模式。