Early onset vs. pre-existing vulnerabilities in adolescent drug use

描述（由申请人提供）：青少年早期使用药物，特别是酒精和烟草，已多次与SUD的后期症状有关。此外，在青春期饮酒与认知功能受损有关，特别是工作记忆能力（WMA）。这些研究结果表明，干预，以防止在青春期早期开始使用药物，可以帮助避免许多不良后果的药物使用，不仅包括SUD，但也损害WMA。尽管有这些证据，但早发性效应的潜在机制仍不清楚。目前的研究旨在澄清这些机制，以便能够得出更确切的预防影响。特别是，以前的研究主要是基于成人的横断面研究，回顾性报告了青少年时期的药物使用情况。这项研究无法确定早期开始使用药物是否仅仅包括药物试验或药物使用的早期进展。早发性假说预测早期进展是后期不良结局的更关键因素。此外，以前的研究表明，早期吸毒只是更普遍的预先存在的脆弱性的一个标志，这些脆弱性增加了青春期后期和成年后出现这些结果的风险。本研究的目的是通过对费城青少年（N=387）的队列进行随访研究，对这些相互竞争的假设进行测试，这些青少年从10-12岁开始，每年由我们的研究团队进行评估，为期5年。费城轨迹研究（PTS）有关于WMA以及不同形式冲动的纵向数据，表明早期使用药物，无论是否导致进展，都与反映WMA弱点的冲动倾向有关。PTS表明，WMA和相关形式的冲动是后期药物不良反应的潜在风险因素，而不是早期开始本身。如果这 假设得到证实，这将表明，早期WMA培训可能是一个有价值的预防策略，以防止药物的不良反应。当队列处于开始使用药物和SUD风险较高的年龄范围（18-19岁）时，拟议的研究对PTS进行了单次随访评估，可以确定药物使用的早期脆弱性是否可以解释早期实验与药物使用进展的差异以及SUD症状的后期开始（目标1）。它还可以确定WMA的早期虚弱和相关形式的冲动是否仍然是与后期药物使用相关的WMA潜在损害的风险因素（目的2）。最后，它可以确定除了药物使用之外的其他不良后果是否可以追溯到WMA的早期弱点，例如问题赌博，反社会行为，性风险和学习成绩差（目标3）。

DESCRIPTION (provided by applicant): Early onset of drug use in adolescence, especially alcohol and tobacco, has been repeatedly linked to later symptoms of SUD. In addition, use of alcohol during adolescence has been linked to impairment of cognitive function, especially working memory ability (WMA). These findings suggest that intervention to prevent the initiation of drug use during early adolescence could help to avert many of the adverse consequences of drug use, including not only SUD but also impairment of WMA. Despite this evidence, the mechanisms underlying the effects of early onset remain unclear. The present research aims to clarify those mechanisms so that firmer implications for prevention can be drawn. In particular, previous research has been based primarily on cross- sectional studies of adults with retrospective reports of drug use during adolescence. This research cannot determine whether early initiation of drug use includes mere experimentation with drugs or only the early progression of drug use. The early onset hypothesis would predict that early progression is the more critical factor for later adverse outcomes. In addition, previous research suggests that early drug use is merely a marker for more general pre-existing vulnerabilities that increase the risks of those outcomes in later adolescence and adulthood. The present research aims to provide a test of these competing hypotheses by conducting a follow-up study of a longitudinal-cohort of Philadelphia adolescents (N=387) that started at ages 10-12 and that were assessed annually for 5 years by our team of researchers. The Philadelphia Trajectory Study (PTS) has longitudinal data on WMA as well as different forms of impulsivity that indicate that early use of drugs, whether it leads to progression or not, is related to impulsive tendencies that reflect weakness in WMA. The PTS suggests that WMA and associated forms of impulsivity are the underlying risk factors for later adverse drug effects rather than early initiation per se. If this hypothesis were confirmed, it would suggest that early WMA training might be a valuable prevention strategy to prevent the adverse effects of drugs. The proposed study with a single follow-up assessment of the PTS when the cohort will be in an age range of high drug-use initiation and risk for SUD (18-19) can determine whether early vulnerabilities for drug use can explain differences in early experimentation vs. progression in drug use as well as later initiatio for symptoms of SUD (Aim 1). It can also determine whether early weakness in WMA and associated forms of impulsivity remain as risk factors for potential impairment in WMA linked to later drug use (Aim 2). Finally, it can determine whether other adverse outcomes apart from drug use are traceable to early weakness in WMA, such as problem gambling, anti-social behavior, sexual risks, and poor academic performance (Aim 3).