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: 8816934
• 负责人: Gregory Evan Miller
• 金额: $ 79.41万
• 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/8816934
• 关键词: Address; Adolescence; Adult; American; Amygdaloid structure; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Attention; Behavior; Behavioral; Biological; Biological Markers; Brain; Buffers; Characteristics; Child Rearing; Childhood; Chronic; Coronary heart disease; Corpus striatum structure; Data; Development; Diffusion Magnetic Resonance Imaging; Disadvantaged; Disease; Economics; Emotional; Enrollment; Evolution; Face; Family; Genetic Transcription; 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; Pathway interactions; Pattern; Phenotype; Poverty; Prefrontal Cortex; Prevention; Process; Proteins; Repression; Research; Resources; Risk; Risk Factors; Self-control as a personality trait; Series; Shapes; Signal Transduction; Sleep; Smoking; Socioeconomic Status; Staging; Statistical Models; Structure; System; Teenagers; Thick; Trust; Violence; Youth; cardiovascular health; cytokine; deprivation; eighth grade; emotion regulation; experience; follow-up; gray matter; heart disease risk; high school; immune function; insight; low socioeconomic status; microbial; mortality; neural patterning; neurodevelopment; optimism; peer; pre-clinical; prospective; 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(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。但这种趋势的强度在不同的人口群体中有所不同。社会经济地位低的人继续发展，并以更典型的20世纪70年代S的比率死于冠心病。大多数关于这些差异的起源的研究集中在生命的中期，即冠心病临床表现的时候。虽然这项研究成果丰硕，但将重点转移到生命的早期阶段可能会产生有价值的见解。许多导致CHD的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CHD的危险因素和临床前症状，这些症状本身就是由SES形成的。尽管有这些发现，但相对较少的注意力集中在早期冠心病的差异上。我们对它们为什么出现以及它们是如何发展的知之甚少。为了解决这些问题，我们建议对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。这些科目将在八年级入学，并在十年级重新评估。根据最近开发的概念框架的假设，该研究提出了关于SES在免疫学、神经和心理社会发育方面的差异以及对早期CHD风险的影响的三个问题。首先，我们问SES是否与免疫系统的成熟模式有关，重点是CHD背后的炎症过程。我们预计低SES的年轻人将表现出多层炎症表型，这在基因组、细胞和系统分析水平上都有体现。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，从而引起行为倾向，从而增加冠心病的风险。利用高维结构成像和扩散张量成像，我们预计低SES与这些回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CHD相关的行为倾向，包括对威胁的警惕、社会动荡、不良的自我调节和不健康的生活方式。最后，注意到SOM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”标准人口统计曲线的特征和经验。我们预计，受到积极社会影响的低社会保障青少年--尤其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--帮助他们更广泛地应对高中生活和低社会保障生活的挑战。这些资源将使SES低的年轻人脱离预期的风险轨迹，导致类似于SES高的年轻人的免疫和神经模式。