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.

项目概要 青春期物质使用的迅速增加给物质和物质的发展带来了风险 因此，确定可塑性风险因素和预防目标。 研究表明，在药物使用开始之前出现是一个重要的公共卫生目标。 折扣（DD），将奖励的价值视为递减的倾向，作为延迟长度的函数 然而，早期发育是药物滥用的一个重要且可改变的风险因素。 DD 的前兆，包括被认为相关的环境逆境和遗传风险因素 现有文献对这些问题的研究尚不清楚。 脆弱性受到限制，因为它依赖于不良环境标志，缺乏 考虑发育影响以及遗传对 DD 发展的贡献。 应用程序建议利用青少年布莱恩认知数据来解决这些限制 发展 (ABCD) 研究，全国青年样本 (n = 11,875)，并计划进行纵向评估 从 9 岁到 17 岁，跨越 DD 和物质使用变化的关键发展时期。 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“ACE 对”框架）和遗传数据来创建 DD 的多基因风险评分 （根据项目进行的最大的 DD 全基因组关联研究的结果 顾问）。项目时间表将利用当前可用的和计划发布的数据。 测试研究目标并加速传播这项具有里程碑意义的研究的具体目标。 研究包括：（目标 1）检查 ACE 的结构及其与早期 DD 水平的关系；（目标 2） 描述 ACE 对 DD 随时间测量轨迹的影响；以及（目标 3）研究 我们还研究了遗传和 ACE 风险因素与青春期 DD 变化的联合关联。 提议探讨 DD 的发育轨迹是否介导遗传与 ACE 之间的关系 研究小组汇集了物质使用频率和严重程度的因素以及随后的变化。 儿童发展、延迟贴现、遗传学和环境风险指标方面的专业知识，允许 关于 DD 的独立和联合背景和遗传贡献的最全面的研究 该项目的研究结果将为 DD 的发展提供机制见解。 除了环境层面的具体和可操作的进步之外，这些进步可能会为目标提供信息 减少高危青少年药物使用的预防方法。