Longitudinal neuroimaging of metamphetamine-dependent adolescents

描述（由申请人提供）：甲基苯丙胺（MA）是美国增长最快的街头毒品。大约有1040万或4.3%的美国人口在他们一生中的某个时候使用过MA。此外，6.2%的高中生在他们的生活中的某个时候使用MA。在韩国，几十年来，MA滥用一直是最普遍的药物滥用形式。对成年MA使用者的结构、神经化学和功能性脑成像研究报告了前额叶皮层的神经生物学缺陷及其在禁欲后的潜在恢复。相反，青春期的MA暴露可能会损害前额叶皮层的正常成熟和修剪，这取决于暴露的特定时间。我们的试点数据表明，青少年MA滥用者（13-18岁）的前额叶灰质变薄，这种赤字与发病年龄呈负相关。在当前提案中，我们将对早发和迟发青少年MA使用者进行基线、6个月和24个月的纵向随访研究，使用脑磁共振成像扫描进行皮质厚度分析，使用弥散张量成像评估白色物质完整性，使用磁共振波谱定量神经元活力。我们的纵向设计很可能提供关于“MA诱导的神经毒性的固定、进展或恢复过程”和“MA对发育中的大脑的影响”的信息。其次，这种多模态成像设计将提供MA诱导的结构和功能性脑缺陷的深入了解。第三，纵向和多模态成像设计的组合提供了MA对大脑发育轨迹的影响的信息。我们的主要研究假设是：1）MA依赖青少年相对于对照组会有前额叶功能障碍，2）早发性青少年MA使用者的前额叶功能障碍比晚发性青少年更大，3）只有早发性而不是晚发性MA滥用者才会观察到戒断恢复。探索性分析还将评估1）MA诱导的神经毒性和神经心理功能障碍之间的关联，以及2）HIV和MA对发育中大脑的潜在联合作用。我们认为，这项研究建议是强烈响应国际研究合作药物成瘾计划公告（PA-07-275），鼓励利用国外存在的独特机会，并强调确保外国配套资金。正如2007年杰出国际科学家奖中对我们团队的认可，我们的有效合作将有助于更好地了解MA滥用对发育中大脑的影响，这将有助于为美国增长最快的街头毒品制定更有效的预防和治疗策略。公共卫生相关性这项针对青少年甲基苯丙胺（MA）依赖受试者的纵向随访神经影像学研究将有助于更好地了解MA滥用对青少年大脑发育的影响。特别是，我们希望评估青少年时期使用MA是否与额叶结构和功能的长期不良影响有关。这些知识将有助于为美国增长最快的街头毒品制定更有效的预防和治疗策略。

DESCRIPTION (provided by applicant): Methamphetamine (MA) is the fastest growing street drug in the United States. Approximately 10.4 million or 4.3% of the US population have used MA at some time in their lives. Also, 6.2% of high school students are reported using MA at some point in their lives. In South Korea, MA abuse has been the most prevalent form of drug abuse for many decades. Structural, neurochemical, and functional brain imaging studies in adult MA users reported neurobiological deficits in the prefrontal cortex and its potential recovery with abstinence. In contrast, MA exposure in adolescence may impair the normal maturation and pruning of the prefrontal cortex, depending on specific times of the exposure. Our pilot data indicates that adolescent MA abusers (13-18 years old) have a thinning in the prefrontal gray matter and that this deficit correlated inversely with age of onset. In the current proposal, we will conduct a longitudinal follow-up study, baseline, 6-month and 24-month, for early and late onset adolescent MA users using brain magnetic resonance imaging scans for cortical thickness analysis, diffusion tensor imaging for assessing white matter integrity and magnetic resonance spectroscopy for quantifying neuronal viability. Our longitudinal design is likely to provide the information on the 'fixed, progressive, or resilient course from MA-induced neurotoxicities' and 'MA effects on the developing brain.' Second, this multimodal imaging design will provide in-depth knowledge of MA-induced structural and functional brain deficits. Third, the combination of longitudinal and multimodal imaging design provides the information the MA's influence on developmental trajectories of the brain. Our main research hypotheses are 1) MA dependent adolescents will have prefrontal deficits relative to controls, 2) early-onset adolescent MA users will have greater prefrontal deficits than late-onset one, and 3) recovery from abstinence will be only observed in the early-onset but not in the late-onset MA abusers. Exploratory analyses will also assess 1) the association between MA-induced neurotoxicities and neuropsychological dysfunction and 2) the potential combined effects of HIV and MA on the developing brain. We believe that this research proposal is strongly responsive to the International Research Collaboration on Drug Addiction in Program Announcement (PA-07-275) that encourages utilization of unique opportunities that exist abroad and places emphasis on securing foreign matching funds. As is also acknowledged in the 2007 Distinguished International Scientist Awards to our team, our efficient collaboration will contribute to a better understanding of the impact of MA abuse on the developing brain, which will help develop more efficacious prevention and treatment strategies for the fastest growing street drug in the United States. PUBLIC HEALTH RELEVANCE This longitudinal follow-up neuroimaging study for adolescent methamphetamine (MA) dependent subjects will contribute to a better understanding of the impact of MA abuse on the developing brain in adolescence. In particular, we wish to evaluate whether MA use during adolescence is associated with long-term adverse effects on frontal lobe structure and function. This knowledge will help develop more efficacious prevention and treatment strategies for the fastest growing street drug in the United States.