Twin Family Study of Vulnerability to Substance Abuse

描述（由申请人提供）：我们寻求继续对由666对双胞胎组成的两个基于人群的队列进行纵向研究和数据分析。较年轻的队列，最初在11岁时招募，在大量使用药物之前，将被跟踪到24-25岁。年龄较大的队列最初在17岁时招募，将在29-30岁时进行评估。我们假设物质使用障碍（SUD）的遗传易感性是通过与行为去抑制和消极情感状态相关的精神、人格、社会心理和心理生理特征来表达的，这些特征可以追溯到青春期前。到目前为止，我们的研究结果表明，外化障碍是高度合并症和家族性的，与约束人格维度有关，并可预测成人反社会行为和sud的发展。这一系列属性是可遗传的，与P3事件相关电位的振幅降低和自主反应性的个体差异有关。然而，我们年轻队列的研究结果表明，在青春期早期，外化和sud的发展存在大量共同的环境贡献，具体的环境因素，如亲子冲突，可能具有病因学意义。消极情绪的人格维度和内化精神病理也与sud的发展有关，但预测的影响不如行为去抑制一致。我们的目标是确定遗传和环境介导的风险因素转化为结果的机制，并了解重要的生活转变如何有助于药物滥用的持续和停止。我们还将建立永生化DNA细胞系，以促进未来研究与SUD表型相关的候选基因，利用潜在生长模型研究SUD发展的相关轨迹，并评估基因环境对其发展的贡献模型。

DESCRIPTION (provided by applicant): We seek to continue the longitudinal study and data analysis of two population-based cohorts consisting of 666 twin pairs. The younger cohort, originally recruited at age 11, prior to significant substance use, will be followed through age 24-25. The older cohort, originally recruited at age 17, will be assessed through age 29-30. We hypothesize that an inherited predisposition to substance use disorder (SUD) is expressed through psychiatric, personality, psychosocial, and psychophysiological characteristics related to behavioral disinhibition and negative affective states that can be traced to pre-adolescence. Our findings to date suggest that externalizing disorders are highly comorbid and familial, associated with the personality dimension of constraint, and predictive of the development of adult antisocial behavior and SUDs. The liability for this collection of attributes is heritable and associated with reduced amplitude of the P3 event-related potential and individual differences in autonomic reactivity. However, findings from our younger cohort indicate that during early adolescence, a substantial shared environmental contribution to the development of externalizing and SUDs is present, with specific environmental factors like parent-child conflict likely to have etiologic significance. The personality dimension of negative emotionality and internalizing psychopathology are also associated with the development of SUDs, but predicted effects are less consistent than for behavioral disinhibition. We aim to identify mechanisms through which genetic and environmentally mediated risk factors translate into outcomes and understand how important life transitions contribute to the persistence and desistance of substance abuse. We will also establish immortalized DNA cell lines to facilitate future studies examining candidate gene associations with SUD phenotypes, investigate trajectories related to the development of SUDs using latent growth modeling, and evaluate models for gene-environment contributions to their development.