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

努力使心理健康和药物使用预防方案个人化，服务不足，贫困 少数族裔青年需要了解社会环境风险因素，这些因素成为生物学上的 嵌入以形成不良健康轨迹的风险。在来自贫困的非裔美国人(AA)青年中 社区、遭受暴力、种族歧视、恶劣的邻里条件和紧张的生活 所有事件都会影响情绪和行为健康问题的风险，包括焦虑和 抑郁、行为/攻击性问题和药物使用。街区的保护性特征 然而，环境可以部分缓解这些风险。应激源产生的生物过程 增加情绪/行为健康不良的风险尚未得到很好的理解，但可能涉及到 表观遗传相关的过程，包括DNA甲基化和端粒长度(TL)。目前的研究 利用了来自高贫困社区的537名AA级青年的特征良好的样本，其中 对生活经历、周围环境、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研究。利用各种尖端方法 跨越行为科学、分子遗传学和统计遗传学，我们将研究全基因组DNA 甲基化和TL作为应激对情绪/行为健康影响的生物中介 一贫如洗的AA青年。我们还测试了增强韧性的保护因素、性别、 和基因，所有这些与甲基化和TL的关系研究不足。我们建议：(1) 确定环境应激源，包括种族歧视、接触暴力和 邻里生态与DNA甲基化和TL有关，反映了 应激；(2)考察甲基化和TL作为应激影响的中介因子的应激连锁变化。 情绪/行为健康；(3)确定社会环境保护因素，包括邻里因素， 这可能会缓冲压力对健康结果的影响，并测试性别差异；(4)探索 在环境应激、甲基化、TL和 情绪/行为健康。这项研究的创新之处在于它同时纳入了个人和社区- 水平预测因素，包括风险和保护因素，以及社会环境和基因在一个困难的- 覆盖贫困AA青年人群。识别应激源和增强复原力的保护因素 与生物变化和行为功能有最强联系的人将有助于开发定制的 为居住在高贫困社区的弱势少数民族青年开展预防性干预工作。

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.