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，但这种关联在多大程度上反映了ADHD的特定因果效应或儿童共病性破坏性疾病的一般贡献仍不确定。性别和ADHD亚型对ADHD和SP之间关系的影响尚未得到充分研究，还需要进行纵向调查，以检查ADHD如何导致SP发展的潜在机制。目前的数据分析建议通过结合三个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物质使用障碍的前景发展。在11 - 17岁期间，对1881对同性青少年进行了常见的儿童和成人心理健康障碍及与SP发展相关的相关危险因素的面对面综合评估。合并后的样本包含了大量的ADHD病例（N=533），包括205名女孩，其中许多是不常被研究的注意力不集中亚型，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检查ADHD、其维度亚型和SP之间关联的一般和特定途径。除了使用生物识别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症状学中的对内不一致性，采用一种新的双胞对照差异设计来检验ADHD和17岁SP之间的关联是否反映了ADHD对SP的因果影响，还是遗传和环境因素对两者的影响。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危险因素，这也可能是她们使用大麻的重要因素。目标2考虑了社会和学业障碍以及内化精神病理在儿童多动症和青春期后期SP发展之间的联系中起中介作用的假设。目的3通过使用潜在类别/生长模型来研究ADHD亚型症状维度在青春期的持续存在如何促进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对尼古丁的发展结果特别重要。因此，该提案解决了重要的理论和实践问题，即ADHD如何通过大型、前瞻性评估、遗传信息丰富的社区代表性样本，使用复杂的分析方法赋予SP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.