Childhood Origins of CHD Disparities: Neural & Immune Pathways

先天性心脏病差异的童年根源：神经性

基本信息

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
项目类别：
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

项目摘要

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。但是，这种趋势的强度在人群群体之间各不相同。社会经济地位低下的人（SES）继续发展并死于1970年代更典型的冠心病。当CHD在临床上表现出来时，大多数关于这些差异起源的研究都集中在寿命的中间阶段。尽管这项研究富有成果，但将重点转移到较早的生活阶段可能会产生宝贵的见解。许多引起冠心病的病原机制始于儿童时期，而随着青春期的增加，美国青年的数量显示了冠心病的危险因素和临床前迹象，而冠心病本身就是SES的模式。尽管有这些发现，但对早期CHD差异的关注很少。我们对它们为什么出现以及它们在发展中的发展知之甚少。为了解决这些问题，我们提出了一项对经济上不同背景的250名青年的预期，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。该研究借鉴了最近开发的概念框架的假设，提出了三个有关免疫，神经和社会心理发展中SES差异的问题，以及对早期CHD风险的影响。首先，我们询问SES是否与免疫系统中的成熟模式有关，重点是炎症过程。我们预计低SES青年会表现出多层炎症表型，该表型表现在基因组，细胞和全身分析水平。其次，我们询问SES是否与大脑皮质骨和皮质纹状体电路中的成熟模式有关，从而引起行为倾向，从而提高了CHD风险。使用高维结构成像和扩散张量成像，我们预计低SES与这些电路中灰色和白色可能性发育的差异有关。这些差异反过来应预示与冠心病相关的行为倾向，包括威胁警惕，社会动荡，自我调节和不健康的生活方式。最后，注意到SOM低SES青年具有积极的健康成果，我们探索了“弯曲”规范性人口曲线的特征和经验。我们预计，遇到积极社会影响（特别是榜样和较高的孕产妇温暖）的低级SES青年将发展一系列个人资源 - 信任，情感调节技能和自尊，这有助于他们更广泛地应对高中和低知名生活的挑战。这些资源将使低调青年从预期的风险轨迹中转移，从而产生与高级SES青年相似的免疫和神经模式。