Relating brain maturation to impulse control and substance use development

说明(由申请者提供)：青少年药物使用很常见，并与严重的个人负面后果和社会的重大代价有关。拟议的研究将利用一个具有成本效益的机会来确定青少年药物使用的潜在风险和后果的神经生物学机制。测试将在有高(n=68)和低(n=34)物质使用障碍家庭风险的青少年中进行，这些测试是从一项正在进行的更大规模的纵向研究中挑选出来的，该研究正在测试冲动控制的发展和物质使用之间的因果关系。在这一新的应用中，我们试图确定额纹状体回路的成熟、冲动控制的发展和青春期参与物质使用的进展之间的关系。我们建议测量11至14岁有物质使用障碍风险的青少年的额纹状体环路，并在5年内每年重复评估。我们将在常规药物使用(目标1)开始之前比较物质使用障碍高风险或低风险青少年之间的回路(目标1)；确定在常规药物使用之前青春期早期额纹状体回路发育的个体差异如何预测物质使用的开始和严重程度(目标2)；并研究额纹状体回路发育的轨迹如何受到家庭风险和青少年物质使用的影响(目标3)。这一应用假设：a)青春期出现的冲动奖赏行为至少部分是由于前额叶皮质延迟成熟而对纹状体调节不足，以及b)青少年特别容易受到物质使用障碍和由此造成的认知障碍的影响。这一框架允许可检验的假设，以检查在青少年发育过程中观察到的冲动控制和物质使用障碍之间潜在的神经生物学机制。这是一个通过检查物质使用障碍潜在风险的神经生物学机制、冲动控制发展以及物质使用对青少年大脑发育的影响来研究青少年物质使用的病因学的机会。我们的研究有一个独特的优势，那就是从一个既定的、特征良好的队列中招募人才，这些队列正在得到纵向跟踪。一支强大的跨学科研究团队已经到位，他们结合了药物滥用研究、先进的成像方法、青少年行为评估和统计建模方面的独特专业知识。这项建议整合了关于大脑发育、青少年行为和药物滥用的不同研究机构，以促进对青少年药物使用的风险和后果的理解。

DESCRIPTION (provided by applicant): Adolescent substance use is common and associated with both significant negative individual consequences and substantial costs to society. The proposed study will capitalize on a cost-effective opportunity to identify neurobiological mechanisms underlying risks for, and consequences of, adolescent substance use. Tests will be conducted in adolescents with high (n= 68) and low (n = 34) familial risk for substance use disorders, selected from a larger ongoing longitudinal study that is testing causal relationships between the development of impulse control and substance use. In this new application, we seek to identify relationships between maturation of frontostriatal circuitry, impulse control development, and progression of substance use involvement across adolescence. We propose to measure frontostriatal circuitry in 11- to 14- year-old adolescents at risk for substance use disorders and to repeat assessments annually for a 5-year period. We will compare circuitry between adolescents at high or low risk for substance use disorders (based on family history) before regular drug use begins (Aim 1); determine how individual differences in early adolescent frontostriatal circuitry development, before regular drug use, predict onset and severity of substance use (Aim 2); and examine how trajectories of frontostriatal circuitry development are affected by both familial risk and adolescent substance use (Aim 3). This application posits that a) impulsive reward- focused behaviors emerging during adolescence are driven, at least in part, by inadequate regulation of the striatum due to delayed maturation of the prefrontal cortex, and b) that adolescents are uniquely vulnerable to substance use disorders and resultant cognitive impairments. This framework allows for testable hypotheses to examine neurobiological mechanisms underlying relationships observed between impulse control and substance use disorders across adolescent development. This is an opportunity to study the etiology of adolescent substance use by examining neurobiological mechanisms underlying risk for substance use disorders, impulse control development, and effects of substance use on adolescent brain development. Our study has the unique advantage of recruiting from an established and well-characterized cohort that is being followed longitudinally. A strong interdisciplinary research team is in place which combines unique expertise in substance abuse research, advanced imaging methodology, adolescent behavioral assessment, and statistical modeling. This proposal integrates distinct bodies of research on brain development, adolescent behavior, and substance abuse to advance understanding of risks and consequences of adolescent substance use.