Epigenetic mechanisms of emotional/behavioral health among impoverished African American youth

贫困非裔美国青年情绪/行为健康的表观遗传机制

• 批准号: 9901362
• 负责人: Darlene A Kertes
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-14 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901362
• 关键词: Adolescence; Adolescent; African American; Aggressive behavior; Alcohol or Other Drugs use; Behavioral; Behavioral Sciences; Biological; Biological Process; Buffers; Characteristics; Communities; DNA Methylation; Development; Dimensions; Ecology; Emotional; Environment; Environmental Impact; Environmental Risk Factor; Epigenetic Process; Event; Exposure to; Face; Family; Future; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genotype; Goals; Health; Human Development; Individual; Knowledge; Length; Life; Life Experience; Link; Low income; Mediating; Mediator of activation protein; Mental Depression; Mental Health; Methodology; Methods; Methylation; Minority; Modeling; Molecular; Neighborhoods; Not Hispanic or Latino; Outcome; Participant; Pathway interactions; Population; Populations at Risk; Poverty; Prevention program; Preventive Intervention; Problem behavior; Process; Race; Reporting; Research; Resources; Risk; Risk Factors; Role; Sampling; Sex Differences; Shapes; Site; Social Environment; Stress; Structure; Testing; Underserved Population; Variant; Violence; Youth; anxiety symptoms; base; behavioral health; behavioral outcome; behavioral phenotyping; cost effectiveness; depressive symptoms; environmental stressor; epigenetic marker; experience; gene environment interaction; genome-wide; genomic locus; indexing; innovation; parental monitoring; personalized approach; protective factors; racial discrimination; racial minority; resilience; sex; social stressor; stressor; substance use prevention; telomere; violence exposure

Efforts to personalize mental health and substance use prevention programs with underserved, impoverished racial minority youth require an understanding of the social environment risk factors that become biologically embedded to shape risk for poor health trajectories. Among African American (AA) youth from impoverished communities, exposure to violence, racial discrimination, poor neighborhood conditions, and stressful life events all impact risk for emotional and behavioral health problems, including symptoms of anxiety and depression, conduct/aggression problems, and substance use. Protective features of the neighborhood environment, however, can partially mitigate these risks. The biological processes by which stressors come to increase the risk for poor emotional/behavioral health is not well understood but likely involve changes in epigenetically-related processes including DNA methylation and telomere length (TL). The present study utilizes a well-characterized sample of 537 AA youth from high-poverty neighborhoods, among whom extensive assessments of life experiences, neighborhood environment, behavioral phenotyping, and genome- wide genetic polymorphisms have already been conducted. Utilizing a variety of cutting-edge methodologies spanning behavioral sciences and molecular and statistical genetics, we will examine genome-wide DNA methylation and TL as biological mediators of stress effects on emotional/behavioral health among impoverished AA youth. We also test for the moderating role of resilience-enhancing protective factors, sex, and genotype, all of which have been understudied in relation to methylation and TL. We propose to: (1) determine whether environmental stressors, including racial discrimination, exposure to violence, and neighborhood ecology are associated with DNA methylation and TL, reflective of a biological embedding of stress; (2) examine stress-linked variations in methylation and TL as mediators of stress effects on emotional/behavioral health; (3) identify social environment protective factors, including neighborhood factors, that could potentially buffer impacts of stress on health outcomes, and test for sex differences; (4) explore the role of genotype as a contributing factor to the relations between environmental stress, methylation, TL, and emotional/behavioral health. This research is innovative for its inclusion of both individual and neighborhood- level predictors, both risk and protective factors, and both social environment and genotype among a difficult- to-reach population of impoverished AA youth. Identifying stressors and resilience-enhancing protective factors with the strongest links to biological changes and behavioral functioning will aid in the development of tailored preventive intervention efforts for vulnerable minority youth residing in high-poverty neighborhoods.

努力个性化的心理健康和物质使用预防计划， 少数民族青年需要了解社会环境的风险因素， 嵌入到塑造健康轨迹不佳的风险。在非洲裔美国人（AA）青年从贫困 社区、暴力、种族歧视、恶劣的社区条件和紧张的生活 所有事件都会影响情绪和行为健康问题的风险，包括焦虑症状， 抑郁、行为/攻击问题和物质使用。邻里的保护特征 然而，环境可以部分缓解这些风险。压力源产生的生物过程 增加不良情绪/行为健康的风险尚未得到很好的理解，但可能涉及 表观遗传学相关的过程，包括DNA甲基化和端粒长度（TL）。本研究 利用了一个良好的特点样本537 AA青年从高贫困社区，其中 对生活经历、邻里环境、行为表型和基因组的广泛评估- 已经进行了广泛的遗传多态性。利用各种尖端方法 跨越行为科学和分子和统计遗传学，我们将研究全基因组DNA 甲基化和TL作为压力对情绪/行为健康影响的生物介质， 一贫如洗的AA青年我们还测试了增强耐受性的保护因素，性别， 和基因型，所有这些与甲基化和TL的关系都研究不足。我们建议：（1） 确定环境压力因素，包括种族歧视，暴力， 邻里生态与DNA甲基化和TL相关，反映了生物嵌入， 应激;（2）检查甲基化和TL作为应激影响的介质的应激相关变化， 情绪/行为健康;（3）识别社会环境保护因素，包括邻里因素， 可以潜在地缓冲压力对健康结果的影响，并测试性别差异;（4）探索 基因型作为环境胁迫、甲基化、TL和 情绪/行为健康。这项研究是创新的，因为它包括个人和邻里- 水平的预测因素，包括危险因素和保护因素，以及社会环境和基因型之间的困难- 帮助那些嗜酒者互诫协会的贫困青年确定压力源和增强依从性的保护因素 与生物变化和行为功能的最强联系将有助于开发定制的 为居住在高度贫困社区的弱势少数群体青年开展预防性干预工作。