An Examination of the Joint Contributions of Socioeconomic Disadvantage, Genetics, and COVID-19 on the Development of Delay Discounting and Substance Use Across Adolescence

社会经济劣势、遗传学和 COVID-19 对青春期延迟贴现和药物使用发展的共同贡献的检验

• 批准号: 10583195
• 负责人: JULIA W FELTON
• 金额: $ 43.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583195
• 关键词: Acute; Address; Adolescence; Adolescent; Adolescent Behavior; Adult; Age; Behavior; COVID-19; COVID-19 pandemic; Child; Child Development; Childhood; Choice Behavior; Chronic; Clinical; Communities; Data; Decision Making; Development; Dimensions; Disadvantaged; Environment; Etiology; Event; Exposure to; Frequencies; Future; Genetic; Genetic Determinism; Genetic Risk; Genetic Variation; Genotype; Goals; Health; Heritability; Individual; Intervention; Investigation; Joints; Length; Link; Literature; Longevity; Longitudinal Studies; Measures; Mediating; Mission; Modeling; National Institute of Drug Abuse; Outcome; Pathway interactions; Pattern; PhenX Toolkit; Play; Poverty; Prevention; Prevention approach; Process; Public Health; Research; Resources; Rewards; Risk; Risk Behaviors; Risk Factors; Role; Sampling; Severities; Shapes; Structure; Substance Use Disorder; Sum; Symptoms; System; Taxes; Testing; Time; TimeLine; Trauma; Youth; adverse childhood events; aged; alcohol use disorder; cognitive development; cost effective; critical developmental period; discounting; environmental stressor; executive function; experience; externalizing behavior; genetic risk factor; genetic variant; genome wide association study; health goals; health inequalities; improved; insight; longitudinal dataset; meetings; modifiable risk; novel; polygenic risk score; preference; reduced substance use; repository; socioeconomic disadvantage; substance misuse; substance use; substance use prevention; trait; trauma exposure

Project Summary Rapid escalations in substance use during adolescence confer risk for the development of substance and alcohol use disorders across the lifespan. Thus, identifying malleable risk factors and prevention targets that emerge before substance use onset is an important public health goal. Research demonstrates that delay discounting (DD), the tendency to perceive diminishing value in a reward as a function of the length of delay in its receipt, is an important and modifiable risk factor for substance misuse. However, the early developmental precursors of DD, including environmental adversity and genetic risk factors that are thought to be associated with increases in DD across adolescence are not well understood. The extant literature examining these vulnerabilities is limited by its reliance on poorly characterized markers of environmental adversity, lack of consideration of developmental effects, and the genetic contributions to the development of DD. The current application proposes to address these limitations utilizing data from the Adolescent Brian Cognitive Development (ABCD) Study, a national sample of youth (n = 11,875) with planned longitudinal assessments from age 9 to 17, spanning critical developmental periods for changes in DD and substance use. The proposed project will leverage rich and varied indicators of adverse childhood events and community environments (using the “Pair of ACEs” framework) and genetic data to create polygenic risk scores for DD (informed by findings from the largest available genome-wide association study of DD performed by project consultants). The project timeline will take advantage of both currently available and planned releases of data to test study aims and accelerate dissemination of findings from this landmark study. Specific aims of the study include: (Aim 1) to examine the structure of ACEs and its relation to early levels of DD; (Aim 2) to characterize the impact of ACEs on measured trajectories of DD over time; and (Aim 3) to investigate the joint associations between genetic and ACEs risk factors on changes in DD across adolescence. We also propose to explore whether developmental trajectories of DD mediate the relation between genetic and ACEs factors and subsequent changes in substance use frequency and severity. The research team brings together expertise in child development, delay discounting, genetics, and environmental indicators of risk, allowing for the most comprehensive study of the independent and joint contextual and genetic contributions to DD development. Findings from this project will provide mechanistic insights into the development of DD, in addition to specific and actionable advancements at the environmental level that may inform targeting of prevention approaches for reducing substance use among at-risk youth.

项目摘要 青春期吸毒的迅速升级会带来吸毒的风险， 酒精使用障碍。因此，确定可塑性风险因素和预防目标， 在药物使用开始之前出现是一个重要的公共卫生目标。研究表明，延迟 折扣（DD），认为奖励价值随着延迟时间的长短而递减的趋势。 它的接收是药物滥用的一个重要和可改变的风险因素。然而，早期发展 DD的前体，包括环境逆境和被认为与DD相关的遗传风险因素 与青少年期DD增加的关系尚不清楚。现存的文献研究这些 脆弱性是有限的，因为它依赖于特征不佳的环境逆境标志，缺乏 考虑发育的影响，以及遗传因素对DD的发展。当前 应用程序建议利用青少年Brian Cognitive的数据来解决这些限制 发展（ABCD）研究，全国青年样本（n = 11 875），计划进行纵向评估 从9岁到17岁，跨越DD和物质使用变化的关键发育期。的 拟议的项目将利用丰富多样的儿童不良事件和社区指标 环境（使用“ACE对”框架）和遗传数据，以创建DD的多基因风险评分 （由项目进行的最大的DD全基因组关联研究的结果提供信息 顾问）。项目时间轴将利用现有和计划发布的数据 测试研究目标，并加速传播这项具有里程碑意义的研究结果。的具体目标 研究包括：（目的1）检查ACE的结构及其与DD早期水平的关系;（目的2） 描述ACE随时间对DD测量轨迹的影响;以及（目标3）调查 遗传和ACE风险因素对青少年DD变化的联合关联。我们也 本研究旨在探讨DD的发育轨迹是否介导了遗传和ACE之间的关系 物质使用频率和严重程度的因素和随后的变化。研究团队汇集了 在儿童发展，延迟折扣，遗传学和风险的环境指标的专业知识，允许 对DD的独立和联合背景和遗传贡献的最全面的研究 发展该项目的研究结果将为DD的发展提供机械的见解， 除了在环境层面取得具体和可采取行动的进展外， 减少高危青年药物使用的预防方法。