Relating brain maturation to impulse control and substance use development

将大脑成熟与冲动控制和物质使用发展联系起来

• 批准号: 8341588
• 负责人: ASHLEY ACHESON
• 金额: $ 47.8万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8341588
• 关键词: 14 year old; Adolescence; Adolescent; Adolescent Behavior; Adolescent Development; Affect; Alcohol or Other Drugs use; Behavior; Behavior assessment; Behavioral; Brain; Corpus striatum structure; Data; Development; Diffusion; Drug usage; Equation; Etiology; Family; Functional Magnetic Resonance Imaging; Image; Impaired cognition; Impulsivity; Individual; Individual Differences; Interdisciplinary Study; Knowledge; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Methodology; Modeling; Prefrontal Cortex; Prevention strategy; Recording of previous events; Recruitment Activity; Regulation; Relative (related person); Research; Research Personnel; Rewards; Risk; Severities; Societies; Spectrum Analysis; Statistical Models; Substance Use Disorder; Substance abuse problem; Testing; Work; adolescent substance use; base; cohort; cost; cost effective; cost effectiveness; design; effective therapy; high risk; myelination; neurobiological mechanism; response; treatment strategy; white matter

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. PUBLIC HEALTH RELEVANCE: 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. This work has important implications for advancing knowledge, and ultimately may contribute to more effective treatment and prevention strategies for adolescent substance use disorders.

描述（由申请人提供）：青少年物质使用很常见，并且与显着的负面个人后果和巨大的社会成本相关。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潜在风险和后果的神经生物学机制。测试将对物质使用障碍家族风险高（n = 68）和低（n = 34）的青少年进行，这些青少年是从一项正在进行的大型纵向研究中选出的，该研究正在测试冲动控制的发展与物质使用之间的因果关系。在这个新应用中，我们试图确定额纹状体回路的成熟、冲动控制的发展和整个青春期物质使用参与进展之间的关系。我们建议测量有物质使用障碍风险的 11 至 14 岁青少年的额纹状体回路，并在 5 年内每年重复一次评估。在开始定期吸毒之前，我们将比较物质使用障碍高风险或低风险青少年（基于家族史）之间的回路（目标 1）；确定常规吸毒前青少年早期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）；并研究家庭风险和青少年药物使用如何影响额纹状体回路发育轨迹（目标 3）。该申请假设：a）青春期期间出现的以奖励为中心的冲动行为至少部分是由于前额皮质成熟延迟导致纹状体调节不足所驱动的；b）青少年特别容易受到药物滥用障碍和由此产生的认知障碍的影响。该框架允许可检验的假设来检查青少年发育过程中冲动控制和物质使用障碍之间观察到的关系的神经生物学机制。这是一个通过检查物质使用障碍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病因学的机会。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进行招募，并进行纵向跟踪。我们拥有强大的跨学科研究团队，结合了药物滥用研究、先进成像方法、青少年行为评估和统计模型方面的独特专业知识。该提案整合了有关大脑发育、青少年行为和药物滥用的不同研究机构，以增进对青少年药物使用风险和后果的了解。 公共卫生相关性：该提案整合了有关大脑发育、青少年行为和药物滥用的不同研究机构，以增进对青少年药物使用风险和后果的了解。这项工作对于增进知识具有重要意义，并最终可能有助于制定更有效的青少年药物使用障碍治疗和预防策略。