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

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的家庭互动 儿童识别遗传和家庭干预对物质使用的影响的关键机制 依赖(SUD)和青春期的心理健康问题。结果将证明 使用现代统计方法分析观测数据，并为规范和改进 更加有力和有效的以家庭为基础的干预措施。我们的方法建立在大样本研究结果的基础上 全基因组关联研究，以告知代表SUD遗传风险的多基因得分的形成 以及对风险家庭关系动态和促进家庭关系动态的不同敏感性。发展理论 关于基因-环境的相互作用突出了需要从只关注简单的主要 效应模型，因此，我们在动态社会互动和随机背景下考察遗传关联 以家庭为基础的干预任务。虽然sud是可遗传的，但它在 有问题的家庭互动和关系。家庭干预是循证的核心 预防和治疗sud的方法和对家庭互动的直接观察是最严格的 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 干预青少年SUD依赖于广泛的总分。最常用的总分是 定义家庭互动可能会简单地错过致病动力学。随着统计学的进步 分析认为，在未来一段时间内，加速观察性家庭研究具有前所未有的潜力 十年。拟议的研究涉及对现有的录像观察进行二次分析 来自早期步骤多点试验的种族/民族多样化的儿童和家庭，应用动态结构 方程建模和多变量多水平生存分析，以了解多基因风险和 下游青少年抑郁与心理健康问题的家庭干预。早期步骤(N=731)是 对以家庭为中心的家庭干预效果进行长期跟踪(2-19岁)的随机试验 体检，关于减少问题行为和SUD。大量数据包括录像观察到的 儿童和父母在2岁、3岁、4岁和5岁的不同背景下。此外，儿童使用 当代Affymetrix Biobank阵列。这些数据提供了一个难得而独特的机会来利用新的 早期习惯性家庭动态与心理健康问题关系的统计学研究 青春期。这些动态机制为加强干预提供了关键的干预目标 这将有助于提高家庭干预的效力和效率，并有助于提高家庭干预的效力。

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.