Genetics and Progression of Early-onset Substance Dependence and HIV Risk

描述（由申请人提供）：本申请中提出的研究旨在了解遗传和环境因素，这些因素促进停止或继续使用有问题的物质以及开始于青春期的相关高风险行为。我们建议随访12年（最初6年随访后6年），一个极度受影响的青少年样本，因为他们过渡到成年;这是一个关键的发展时期，当我们期望这些个体中的一部分减少或停止有问题的物质使用和相关的高风险行为时，而其他人将坚持最严重的，破坏性行为导致了极高的发病率和死亡率。我们的中心目标是了解描述这些生命轨迹的遗传和环境因素。我们的纵向研究结果表明，在青春期主要表现出滥用和依赖大麻、尼古丁和酒精的成瘾性物质使用者，在五年后其物质使用的严重程度有所进展。作为年轻的成年人，他们报告终身可卡因（29.2%），安非他明（29.2%）和阿片类药物（10.8%）使用障碍以及艾滋病毒/艾滋病相关的风险行为，如注射毒品使用（11%）和危险的性行为。事实上，与社区样本相比，这些人报告的终身性伴侣数量是社区样本的两倍多，无保护性行为的比例高出33%。此外，他们的成年监禁率（55%）和早逝率（2.6%）令人震惊。这项建议扩展了我们的多PI合作，重点是遗传流行病学的初发性药物依赖。这三个具体目标是：1）确定从青春期到成年期先证者和兄弟姐妹中物质使用、反社会和艾滋病毒风险行为的不同发展轨迹。a）测试青少年的初始特征，例如性别、早发性物质使用障碍（SUD）和行为障碍（CD）的严重程度以及神经认知功能（例如，去抑制）来预测这些轨迹 和B）测试成人资源（如SUD治疗、住房稳定性、职业稳定性和社会支持）是否与这些轨迹相关。2)确定物质使用障碍，反社会和艾滋病毒风险行为的发展轨迹的遗传和环境结构。a）测试社会背景的调节作用，如社会经济地位，刑事司法参与，物质滥用治疗/自助参与，和压力的生活事件，在改变遗传影响和B）测试调节作用是否在不同的发展阶段（青春期，青年期和成年期）。3)测试共同与特定病因学影响对SUD、反社会行为和HIV风险行为的影响。

DESCRIPTION (provided by applicant): The research proposed in this application aims to understand genetic and environmental factors that promote desistance or continuation of problematic substance use and associated high-risk behaviors that began in adolescence. We propose an ~12-year follow-up (6 years after an initial 6-year follow-up) of an extremely affected adolescent sample as they transition into adulthood; this is a critical developmental period when we expect a portion of these individuals to decrease or desist problematic substance use and associated high-risk behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high rates of morbidity and mortality. Our central goal is to understand the genetic and environmental factors that delineate these life trajectories. Results from our longitudinal research demonstrate that adolescent-onset substance users, who primarily exhibited abuse of and dependence on marijuana, nicotine, and alcohol during adolescence, progressed in the severity of their substance use five years later. As young adults, they report dramatically high rates of lifetime cocaine (29.2%), amphetamine (29.2%), and opiate (10.8%) use disorders as well as HIV/AIDS-related risk behaviors such as injection drug use (11%) and risky sexual behaviors. Indeed, when compared with community samples, these individuals report more than twice the number of lifetime sexual partners and a 33% higher rate of unprotected sex. Furthermore, they exhibit alarming rates of adult incarceration (55%) and early death (2.6%). This proposal extends our multiple-PI collaboration focused on the genetic epidemiology of adolescent-onset drug dependence. The three specific aims are to: 1) Identify distinct developmental trajectories of substance use, antisocial, and HIV risk behaviors in probands and siblings from adolescence to adulthood. a) Test initial characteristics of the adolescents, such as sex, severity of early onset substance use disorders (SUDs) and conduct disorder (CD), and neurocognitive functioning (e.g., disinhibition) that predict these trajectories and b) Test whether adult resources such as treatment for SUDs, housing stability, occupational stability, and social support are associated with these trajectories. 2) Determine the genetic and environmental architecture of developmental trajectories of substance use disorders, antisocial and HIV risk behaviors. a) Test the moderating role of social context, such as SES, criminal justice involvement, substance abuse treatment/self-help involvement, and stressful life events, in altering genetic influence and b) Test whether moderating effects vary across developmental periods (adolescence, young adulthood, and adulthood). 3) Test the influence of shared versus specific etiologic influences on measures of SUDs, antisocial behaviors, and HIV risk behaviors across development.