Leveraging Bifactor Modeling to Test Prospective Direct and Mediational Effects of Adolescent Alcohol Use and Externalizing Symptoms on the Neurobiological Development of Executive Functioning

7.项目总结/摘要 青春期是大脑基本成熟的时期。考虑到神经生物学的发展， 在这一时期发生的，研究人员，政策制定者和父母的一个中心问题是 青少年酒精使用（Au）对认知能力的影响对生活的成功至关重要，如执行功能（EF）。EF 是指一系列自上而下的心理过程，支持注意力、注意力和行为 条例44. EF的健康发展对身心健康、学业成就、 and success成功in life 31，32.已经提出青少年Au产生生理和神经生物学 导致健康EF发育脱轨的事件18，30。然而，对这一协会的支持有好有坏8，35。 模棱两可的支持可能是由于（1）过去的工作失败，考虑Au在更广泛的背景下，外部化 症状和社会发展33 -35，和（2）缺乏神经影像学和行为任务措施的EF 20，36。 青少年Au通常发生在更广泛的外部症状（违反规则，攻击）和 其他药物的使用38，有证据表明，外化症状破坏EF的健康发展， 一个发展级联，涉及在多个环境（父母，同龄人，学校）适应不良16，17。 同时发生的药物使用也可能具有使EF脱轨的直接神经毒性作用7，13，18。因此，可怜的EF， 归因于青少年Au的神经毒性作用，实际上可能是由于这些其他共同发生的 行为。此外，对AU-EF相关性的不明确支持可能是由于相当大的异质性 测量EF 36。不存在评估EF的“纯过程”措施102。因此，多方法 方法是必不可少的102，成瘾理论断言，使用神经成像是至关重要的， 和任务方法来测量EF 101。该奖学金旨在澄清AU-EF文献。我们 建议（1）区分一般外化症状和领域特异性症状（包括Au， 侵略，违反规则，吸毒）使用复杂的纵向双因素建模，（2）检查 一般外化症状和领域特异性症状与EF之间的前瞻性关联 （通过功能磁共振成像和行为任务测量）在青春期和成年早期，（3）检查是否 在几个社会背景（父母，同龄人和学校）之间的适应不良介导了 外化症状和EF缺陷。酗酒者子女的高风险纵向样本（N= 3，337） 密歇根州纵向研究将用于测试拟议的aims 46。数据将包括以下人员的自我报告： 功能磁共振成像扫描期间的Au、药物使用、外化症状和社会功能以及EF行为任务 从青少年早期到成年早期的四个阶段。我们的纵向数据将使我们能够检查 当EF的风险和保护因素可能特别突出时，告知干预的时机。结果 将促进我们对Au和共同发生的外部症状以及社会适应的理解 影响EF发展的轨迹，并可能确定促进健康EF的重要干预目标。

7. PROJECT SUMMARY/ABSTRACT Adolescence is a period of substantial brain maturation30. Considering the neurobiological development that occurs during this period, a central concern to researchers, policy makers, and parents is the impact of adolescent alcohol use (AU) on cognitive capacities critical to life success, like executive functioning (EF). EF refers to a family of top-down mental processes that support concentration, attention, and behavioral regulation44. Healthy development of EF is essential for mental and physical health, academic achievement, and success in life31,32. It has been proposed that adolescent AU produces physiological and neurobiological events that derail healthy EF development18,30. However, support for this association has been mixed8,35. Equivocal support may be due to (1) failure of past work to consider AU in the broader context of externalizing symptoms and social development33-35, and (2) lack of neuroimaging and behavioral task measures of EF20,36. Adolescent AU often occurs in a broader context of externalizing symptoms (rule-breaking, aggression) and other drug use38, and there is evidence that externalizing symptoms disrupt healthy development of EF through a developmental cascade that involves poor adaptation across multiple contexts (parenting, peers, school)16,17. Co-occurring drug use may also have direct neurotoxic effects that derail EF7,13,18. Hence, poor EF that has been attributed to the neurotoxic effects of adolescent AU may actually be due to these other co-occurring behaviors. Additionally, equivocal support for the AU-EF association may be due to considerable heterogeneity in measurement of EF36. No ‘‘process-pure’’ measures to assess EF exist102. Therefore, multimethod approaches are essential102 and theories of addiction assert that it is critically important to use neuroimaging and task methods to measure EF101. This fellowship seeks to provide clarity to the AU-EF literature. We propose to (1) distinguish general externalizing symptoms from domain specific symptoms (including AU, aggression, rule-breaking, drug use) using sophisticated longitudinal bifactor modeling, (2) examine prospective associations between general externalizing symptoms and domain specific symptoms, and EF (measured by fMRI and a behavioral task) across adolescence and early adulthood, and (3) examine whether poor adaptation across several social contexts (parents, peers, and school) mediates associations between externalizing symptoms and deficits in EF. A high-risk longitudinal sample (N=3,337) of children of alcoholics from the Michigan Longitudinal Study will be used to test the proposed aims46. Data will include self-reports of AU, drug use, externalizing symptoms, and social functioning, and an EF behavioral task during fMRI scanning at four waves spanning early adolescence to early adulthood. Our longitudinal data will allow us to examine when risk and protective factors to EF may be especially salient, informing the timing of interventions. Results will advance our understanding of how AU and co-occurring externalizing symptoms, and social adaptation impact trajectories of EF development, and may identity important intervention targets to promoting healthy EF.