Twin Study of ADHD, CD and Substance Abuse

描述(由申请人提供)：受遗传影响的儿童破坏性障碍，如注意力缺陷多动障碍(ADHD)、品行障碍(CD)和对立违抗障碍(ODD)，一直与物质使用障碍(SUDS)的后期发展有关。然而，关于遗传影响的机制，或者遗传因素如何与特定的环境风险结合在一起，在这些疾病的产生、维持和发展到肥胖症的过程中，人们知之甚少。我们寻求五年的更新资金，以便我们可以努力解释这些发展进程。我们收集了大量的以社区为基础的青春期前样本，男性和女性的代表性均等，这些样本已经丰富了ADHD、CD和ODD的存在。我们的样本由双胞胎和他们的父母组成，具有遗传信息，提供了双胞胎数据的生物统计模型以及父母-后代传播效应的模型，我们获得了所有参与者的DNA样本。我们还使用自我报告和面谈的方法评估了一系列可能的体验风险，包括亲子关系、父母监控、社会支持网络、邻里条件、学校相关经历和同龄人群体特征，涉及多个告密者(父母、儿童、教师)。因此，结合起来，我们有可能解决有关ADHD、CD、ODD和SODS之间关系的重要假说，包括那些结合了基因-环境相关性和基因-环境相互作用理论的假说。我们最初的资金让500对11岁的双胞胎和他们的父母完成了为期一天的InPerson评估。他们14岁时的第一次后续评估已经开始。申请的额外五年资助将允许完成14岁的评估，并在17岁时对其中大多数人进行重新评估。这一丰富的样本与我们正在进行的其他研究项目的病例相结合，将在14岁之前产生250多名ADHD患者和600名CD患者。这一高风险样本将拥有全面的纵向数据，非常适合调查性别影响。在接下来的五年里，我们的目标是了解基因与环境的相互作用，最终导致物质滥用和早发性肥胖症。为了实现这一目标，我们将致力于：1)表征SUD的遗传脆弱性，包括心理生理学指标和候选基因所起的作用；2)了解青少年早期问题行为如何影响SUD的发展过程；3)描述家庭内外社交因素的作用；4)澄清消极情绪性的作用；5)解决有关性别的作用，包括遗传脆弱性是否因性别而异，以及性别是否调节责任标记、环境风险和后来的药物使用问题之间的联系。

DESCRIPTION (provided by applicant): Genetically influenced childhood disruptive disorders, such as attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) have been consistently associated with the later development of substance-use disorders (SUDs). Yet relatively little is known about the mechanisms of genetic influence, or how genetic factors combine with specific environmental risks in the creation of these disorders, their maintenance, and their progression on to SUDs. Five years of renewal funding is sought so that we may work to explicate these developmental processes. We have collected a large, community-based pre-adolescent sample, with equal representation of males and females that has been enriched for the presence of ADHD, CD, and ODD. Composed of twins and their parents, our sample is genetically informative, providing for biometric modeling of the twin data as well as modeling of parent-offspring transmission effects and we obtain DNA samples on all participants. We also assess a wide array of possible experiential risks, including parent-child relationships, parental monitoring, social support networks, neighborhood conditions, school-related experiences, and peer-group characteristics using self-report and in person interview methods involving multiple informants (parents, children, teachers). Thus, in combination, we have the potential to address important hypotheses regarding the relationship between ADHD, CD, ODD and SUDs, including those that incorporate theories of gene-environment correlation and gene-environment interaction. Our initial funding allowed 500 pairs of 11-year-old twins and their parents to complete a day-long, inperson assessment. Their first follow-up assessment, at age 14, has begun. The additional requested five years of funding will allow for the completion of the age-14 assessment as well as the re-assessment of most of these individuals at age 17. The combination of this enriched sample with cases from our other ongoing research projects will yield more than 250 individuals with ADHD and 600 with CD by age 14. This high-risk sample will have comprehensive, longitudinal data and is well suited to investigate gender effects. During the next five years, we aim to understand gene-environment interplay that culminates in substance misuse and early-onset SUDs. Towards this goal we will work to: 1) characterize the inherited vulnerability for SUDs, including the role psychophysiological indicators and candidate genes play; 2) learn how early adolescent problem behaviors influence the course of SUD development; 3) delineate the role of intra and extra-familial socializing agents; 4) clarify the role of negative emotionality; and 5) address questions regarding the role of gender, including whether the inherited vulnerability varies by gender, and whether gender moderates the association between liability markers, environmental risk, and later substance-use problems.