Relating brain maturation to impulse control and substance use development

描述（由申请人提供）：青少年药物使用是常见的，并与显着的负面个人后果和社会的巨大成本。拟议的研究将利用一个具有成本效益的机会，以确定神经生物学机制的潜在风险，和后果，青少年物质使用。测试将在具有高（n= 68）和低（n = 34）物质使用障碍家族风险的青少年中进行，这些青少年选自一项正在进行的大型纵向研究，该研究正在测试冲动控制和物质使用之间的因果关系。在这个新的应用程序中，我们试图确定成熟的额纹状体电路，冲动控制的发展，并在整个青春期的物质使用参与的进展之间的关系。我们建议测量11至14岁的青少年在物质使用障碍的风险额纹状体电路，并每年重复评估，为期5年。我们将比较高风险或低风险的青少年之间的物质使用障碍的电路（基于家族史）在常规药物使用开始之前（目标1）;确定在常规药物使用之前，早期青少年额纹状体回路发育的个体差异如何预测物质使用的发作和严重程度（目标2）;并研究额纹状体回路发展的轨迹如何受到家族风险和青少年物质使用的影响（目标3）。该申请假定：a）在青春期出现的冲动性奖励集中行为至少部分地由由于前额叶皮层的延迟成熟引起的纹状体调节不足所驱动，以及B）青少年特别容易受到物质使用障碍和由此产生的认知障碍的影响。这个框架允许可检验的假设，以检查神经生物学机制之间的关系观察到的冲动控制和物质使用障碍在青少年的发展。这是一个机会来研究青少年物质使用的病因学，通过检查物质使用障碍，冲动控制的发展，物质使用对青少年大脑发育的影响的潜在风险的神经生物学机制。我们的研究具有独特的优势，即从一个已建立且特征良好的队列中招募，并对其进行纵向随访。一个强大的跨学科研究团队已经到位，它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的独特专业知识。该提案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.