Parent-Child Interaction Dynamics Mediate Genetic and Prevention Effects on the Development of Adolescent Substance Use Disorders

亲子互动动态介导遗传和预防对青少年药物使用障碍发展的影响

• 批准号: 10362050
• 负责人: Kathryn Lemery-Chalfant
• 金额: $ 50.28万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10362050
• 关键词: Adolescence; Adolescent Development; Affect; Age; Behavioral; Child; Child Development; Code; Computer software; Data; Data Analyses; Data Analytics; Development; Distal; Effectiveness of Interventions; Environment; Equation; Ethnic Origin; Family; Family Relationship; Family Research; Family dynamics; Future; Genes; Genetic; Genetic Risk; Genotype; Goals; Heritability; Home; Intervention; Investigation; Lead; Link; Longitudinal Studies; Longterm Follow-up; Measures; Mediating; Mediation; Mental Health; Methodology; Methods; Modeling; Modernization; Outcome; Parent-Child Relations; Parents; Pathogenicity; Pattern; Predisposition; Prevention; Problem behavior; Process; Race; Randomized; Randomized Controlled Trials; Reporting; Research; Risk; Role; Sampling; Social Desirability; Social Interaction; Social Processes; Statistical Data Interpretation; Statistical Methods; Stress; Substance Addiction; Substance Use Disorder; Survival Analysis; Testing; Time; Videotape; adolescent substance use; anti social; antisocial behavior; base; biobank; biological sex; biological systems; checkup examination; dosage; early childhood; effective intervention; ethnic diversity; evidence base; genetic association; genome wide association study; improved; intervention effect; multi-site trial; next generation; prevent; prognostic; racial and ethnic; randomized trial; resilience; secondary analysis; social; social influence; substance use; theories

Abstract Our overarching goal is to use new quantitative methods of capturing dynamic family interactions in early childhood to identify key mechanisms underlying genetic and family intervention effects on substance use and dependence (SUD) and mental health problems across adolescence. Results will demonstrate the value of observational data analyzed with modern statistical approaches and inform the specification and refinement of more potent and effective family-based interventions. Our approach builds on findings from large sample genome wide association studies to inform formation of polygenic scores that represent genetic risk for SUD and differential susceptibility to both risky and promotive family relationship dynamics. Developmental theory on gene-environment interplay has highlighted the need to move away from focusing only on simple main effect models, thus, we examine genetic association in the context of dynamic social interactions and random assignment to a family-based intervention. Although SUD is heritable, it develops and progresses within problematic family interactions and relationships. Family interventions are central to evidence-based approaches to preventing and treating SUD, and direct observation of family interactions is the most rigorous way of measuring family interactions. To date, the methodology and analysis of family interactions relevant to intervening on youth SUD relies on broad aggregate scores. The most commonly used aggregate scores that define the family interaction may simply miss pathogenic dynamics. With the advancement of statistical analyses, there is unprecedented potential for accelerating observational family research over the coming decade. The proposed study involves secondary analysis of existing videotaped observations of racially/ethnically diverse children and families from the Early Steps Multisite Trial, applying dynamic structural equation modeling and multivariate multilevel survival analysis to understand the effects of polygenic risk and family intervention on downstream adolescent SUD and mental health problems. Early Step (N=731) is a randomized trial with long-term follow-up (ages 2-19) of the effects of the family-centered intervention, Family Check-Up, on reducing problem behaviors and SUD. The extensive data include videotaped observations of children and parents across multiple contexts at ages 2, 3, 4, and 5. In addition, children were genotyped using the contemporary Affymetrix Biobank Array. Such data provide a rare and unique opportunity to utilize new statistical methods to understand early habitual family dynamics on SUD and mental health problems in adolescence. These dynamic mechanisms provide key intervention targets for enhancing intervention effectiveness and efficiency and lead to enhancing potency of family-based interventions.

摘要 我们的首要目标是使用新的定量方法来捕捉早期动态家庭互动， 确定遗传和家庭干预对药物使用影响的关键机制， 依赖（SUD）和青少年心理健康问题。结果将证明 用现代统计方法分析观测数据，并为规范和改进提供信息。 更有力和有效的家庭干预措施。我们的方法建立在大样本调查结果的基础上 全基因组关联研究，为代表SUD遗传风险的多基因评分的形成提供信息 以及对危险和促进性家庭关系动态的不同易感性。发展理论 关于基因与环境相互作用的研究强调了从仅仅关注简单的主要因素转向 因此，我们在动态社会互动和随机的背景下研究遗传关联。 分配到以家庭为基础的干预。虽然SUD是可遗传的，但它在体内发展和进展。 有问题的家庭互动和关系。家庭干预是循证医学的核心 预防和治疗SUD的方法，直接观察家庭互动是最严格的 衡量家庭互动的方式。到目前为止，有关家庭互动的方法和分析， 对青年的未成年人吸毒问题进行干预依赖于广泛的综合评分。最常用的综合得分， 定义家庭相互作用可能只是错过致病动力。随着统计学的进步， 分析，在未来加速观察家庭研究的潜力是前所未有的。 十年拟议的研究涉及对现有的录像观察的二次分析， 种族/民族多样化的儿童和家庭从早期步骤多地点试验，应用动态结构 方程建模和多变量多水平生存分析，以了解多基因风险的影响， 下游青少年SUD和心理健康问题的家庭干预。早期步骤（N=731）是一个 一项长期随访（2-19岁）的以家庭为中心的干预效果的随机试验， 检查，减少问题行为和SUD。广泛的数据包括录像观察， 在2岁、3岁、4岁和5岁时，儿童和父母在多个环境中。此外，儿童的基因分型使用 当代Affyoung生物银行阵列。这些数据提供了一个难得的和独特的机会，利用新的 统计方法来了解早期习惯性家庭动力学对SUD和心理健康问题的影响， 青春期这些动态机制为加强干预提供了关键的干预目标 提高效率和效力，并导致增强以家庭为基础的干预措施的效力。