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

描述(由申请人提供)：ADHD一直被认为与青少年滥用尼古丁、酒精和大麻有关的物质问题(SP)的发展有关，但目前仍不确定这种联系在多大程度上反映了ADHD的特定因果关系，或者在多大程度上反映了并发的儿童破坏性障碍的一般贡献。性别和ADHD亚型效应一直未得到充分研究，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结合了三项以社区为基础的家庭研究的数据，这些研究侧重于青少年双胞胎药物使用障碍的预期发展，从而解决了这些重要的公共卫生问题。招募的1881对同性青少年对11至17岁之间常见的儿童和成人心理健康障碍及其相关风险因素进行了面对面的全面评估。合并后的样本包含大量ADHD病例(N=533)，其中包括205名女孩，其中许多人较少被研究注意力不集中亚型，这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研究ADHD、其维度亚型和SP之间潜在的一般和特殊通路。除了使用生物测定模型来评估遗传和环境对观察到的关系的贡献外，我们还利用ADHD症状学中的对内不一致性，应用一种新的同双胞胎对照差异设计来检验ADHD和AGE-17 SP之间的关联是反映了ADHD对SP的因果影响，还是反映了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显著的风险因素，这可能也是她们使用大麻的重要原因。目的2研究儿童ADHD与青春期晚期SP发展之间的关系，认为社会和学业障碍与内化精神病理学共同调节儿童ADHD与SP发展之间的联系。目的3通过研究ADHD亚型症状维度在整个青春期的持续性如何利用潜在的班级/成长模型来促进SP的发展，从而解决了文献中的另一个空白。我们假设，持续的注意力不集中症状将对尼古丁结果的发展特别重要。因此，该提案解决了有关ADHD如何利用复杂的分析方法与大的、前瞻性评估的、遗传信息丰富的社区代表样本相结合的方式增加SP风险的重大理论和实践问题。

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.