ADHD and Substance Problems in Adolescence: Specificity, Mechanisms, and Gender

描述（由申请人提供）：ADHD一直与青少年滥用尼古丁、酒精和大麻相关的物质问题（SP）的发展有关，但仍不确定这种关联在多大程度上反映了ADHD的特定因果效应或共病儿童破坏性障碍的一般贡献。性别和ADHD亚型的影响已经研究不足，因为它们与ADHD和SP之间的联系有关，还需要进行纵向调查，研究ADHD如何导致SP发展的潜在机制。目前的数据分析提案通过结合三项以社区为基础的家庭研究的数据来解决这些重要的公共卫生问题，这些研究的重点是青少年双胞胎药物使用障碍的前瞻性发展。招募的1881对同性青少年样本进行了面对面的综合评估，评估了11至17岁儿童和成人常见的心理健康障碍以及与SP发展相关的相关风险因素。合并样本包含大量的ADHD病例（N=533），其中包括205名女孩，许多人较少研究注意力不集中的亚型，使我们能够评估性别和ADHD亚型在三个特定目标中的影响。目的1检查ADHD及其维度亚型与SP之间关联的一般和特定途径。除了采用生物计量模型来评估遗传和环境对观察到的关系的贡献外，我们利用ADHD行为学中的配对内不一致性，应用一种新的双胞胎对照差异设计来研究ADHD与年龄之间的关联，17 SP反映了ADHD对SP的因果影响，或影响两者的遗传和环境影响的影响。我们假设注意力不集中是女孩尼古丁依赖的一个特别突出的风险因素，这也可能是她们使用大麻的重要因素。目的2认为，社会和学术障碍与内化的精神病理学调解儿童多动症和随后的发展SP青春期后期之间的联系的假设。目的3解决了文献中的另一个空白，通过研究如何持续性的ADHD亚型症状维度，通过青春期有助于SP的发展，使用潜在的类/增长模型。我们推测，持续的注意力不集中症状对尼古丁结果的发展尤为重要。因此，该提案解决了重要的理论和实践问题，即ADHD如何使用复杂的分析方法，通过大量的前瞻性评估，遗传信息丰富的社区代表性样本，为SP提供风险。

DESCRIPTION (provided by applicant): ADHD has been consistently implicated in the development of substance problems (SP) related to adolescent misuse of nicotine, alcohol, and marijuana, but it remains uncertain to what degree this association reflects a specific causal effect of ADHD or a general contribution of comorbid childhood disruptive disorders. Gender and ADHD subtype effects have been understudied as they relate to the link between ADHD and SP, and longitudinal investigations that examine underlying mechanisms indicating how ADHD leads to the development of SP are also needed. The present data analysis proposal addresses these important public health questions by combining data from three community- based family studies focused on the prospective development of substance use disorders in adolescent twins. The recruited sample of 1881 same-sex adolescent pairs has undergone in-person comprehensive assessments of common childhood and adult mental health disorders and associated risk factors relevant to the development of SP from ages 11 to 17. The combined sample contains a substantial number of ADHD cases (N=533), including 205 girls, many with the less often studied inattentive subtype, allowing us to evaluate effects of both gender and ADHD subtype in each of three specific aims. Aim 1 examines general and specific pathways underlying the association between ADHD, its dimensional subtypes, and SP. In addition to employing biometric modeling to evaluate the genetic and environmental contributions to the observed relationships, we take advantage of the within-pair discordance in ADHD symptomatology to apply a novel co-twin control difference design to examine whether the association between ADHD and age-17 SP reflects the causal impact of ADHD on SP or the impact of genetic and environmental influences affecting both. We hypothesize that inattention constitutes a specifically salient risk factor for nicotine dependence in girls, one that may also figure importantly in their use of cannabis. Aim 2 considers the hypothesis that social and academic impairment together with internalizing psychopathology mediate the link between childhood ADHD and the subsequent development of SP by late adolescence. Aim 3 addresses another gap in the literature by examining how the persistence of ADHD subtype symptom dimensions through adolescence contributes to the development of SP using latent class/growth models. We hypothesize that persisting inattentive symptoms will be particularly important to the development of nicotine outcomes. The proposal thus addresses significant theoretical and practical questions regarding how ADHD confers risk for SP using sophisticated analytic approaches with a large, prospectively assessed, genetically informative community representative sample.