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

描述(由申请人提供)：青春期早期使用药物，特别是酒精和烟草，多次被认为与后来的sud症状有关。此外，青春期饮酒与认知功能受损有关，特别是工作记忆能力(WMA)。这些发现表明，预防在青春期早期开始使用药物的干预措施可以帮助避免药物使用的许多不良后果，不仅包括SUD，还包括WMA的损害。尽管有这些证据，但早发的影响背后的机制仍然不清楚。本研究旨在澄清这些机制，以便对预防产生更明确的影响。特别是，以前的研究主要是基于对成年人的横断面研究，并回顾了青春期使用药物的报告。这项研究无法确定早期开始使用药物是否包括单纯的药物试验，或仅包括药物使用的早期进展。早期发病假说将预测早期进展是导致较晚不良后果的更为关键的因素。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，这些脆弱性会增加青春期后期和成年后出现这些结果的风险。本研究旨在通过对费城青少年(N=387)的纵向队列进行跟踪研究来检验这些相互竞争的假设，该研究从10-12岁开始，由我们的研究团队每年进行为期5年的评估。费城轨迹研究(PTS)拥有关于WMA的纵向数据以及不同形式的冲动，这些数据表明，早期使用药物，无论是否导致进展，都与反映WMA虚弱的冲动倾向有关。PTS表明，WMA和相关形式的冲动是后来药物不良反应的潜在风险因素，而不是早期启动本身。如果这个 假说得到证实，提示早期WMA训练可能是预防药物不良反应的一种有价值的预防策略。拟议的这项研究只对PTS进行一次后续评估，当队列将处于开始吸毒和SUD风险较高的年龄段(18-19岁)时，可以确定早期吸毒的脆弱性是否可以解释早期试验与药物使用进展以及后来开始SUD症状的差异(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来使用药物有关的WMA潜在损害的风险因素(目标2)。最后，它可以确定除吸毒外的其他不良后果是否可追溯到WMA早期的弱点，如问题赌博、反社会行为、性风险和学习成绩不佳(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).