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

项目摘要 青春期物质使用的迅速增加增加了物质和精神发育的风险 终生酒精使用障碍。因此，确定具有延展性的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 贴现(DD)，认为奖励的价值递减是延迟时间长短的函数 它的接收，是物质滥用的一个重要的、可改变的风险因素。然而，早期发育 DD的先兆，包括被认为与环境逆境和遗传风险因素有关的 随着青春期DD的增加，人们还不太清楚。研究这些问题的现存文献 脆弱性受限于它对环境逆境的不良特征标记的依赖，缺乏 考虑发育效应，以及遗传因素对发育迟缓的影响。海流 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)，有计划的纵向评估 从9岁到17岁，跨越DD和物质使用变化的关键发育期。这个 拟议的项目将利用丰富多样的不良童年事件和社区指标 环境(使用“一对王牌”框架)和遗传数据为DD创建多基因风险分数 (由Project执行的关于DD的最大可用全基因组关联研究的结果提供信息 顾问)。项目时间表将利用目前可用的和计划的数据发布 测试研究目标并加速传播这项里程碑式的研究结果。《公约》的具体目标 研究包括：(目标1)检查ACE的结构及其与早期发育迟缓水平的关系；(目标2) 描述ACE对DD随时间测量的轨迹的影响；以及(目标3)调查 遗传和ACE危险因素对青春期DD变化的联合关联。我们也 建议探索DD的发展轨迹是否在遗传和ACE之间起中介作用 物质使用频率和严重程度的因素和随后的变化。研究小组汇集了 在儿童发展、延迟折扣、遗传学和环境风险指标方面的专业知识，允许 对独立和联合的背景和遗传因素对DD的贡献的最全面的研究 发展。这个项目的发现将为发展DD提供机械性的见解，在 除了环境层面的具体和可操作的进展外，可能会为目标提供信息 减少高危青少年使用药物的预防方法。

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.