Longitudinal neuroimaging of metamphetamine-dependent adolescents

甲基苯丙胺依赖青少年的纵向神经影像学

• 批准号: 8279384
• 负责人: In Kyoon Lyoo
• 金额: $ 26.12万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279384
• 关键词: 15 year old; 18 year old; Abstinence; Accounting; Adolescence; Adolescent; Adult; Adverse effects; Age; Age of Onset; American; Area; Award; Blood; Brain; Brain imaging; Brain region; Caring; Cerebrum; Chemistry; Clinical; Clinical Research; Collaborations; Communities; Comorbidity; Country; Data; Development; Developmental Process; Diffusion Magnetic Resonance Imaging; Disease; Drug Addiction; Drug abuse; Enrollment; Epidemic; Functional disorder; Funding; Glucose; Grant; HIV; HIV Infections; HIV Seropositivity; Health; Hospitals; Human; Illicit Drugs; Image; Imaging Techniques; International; Knowledge; Korea; Koreans; Lead; Letters; Life; Location; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Marijuana; Measures; Methamphetamine; Mission; Multimodal Imaging; NIH Program Announcements; National Institute of Drug Abuse; Neurobiology; Neurons; Paper; Pattern; Pharmaceutical Preparations; Population; Prefrontal Cortex; Prevention strategy; Protons; Publishing; Recovery; Recruitment Activity; Relative (related person); Reporting; Request for Applications; Research; Research Design; Research Personnel; Research Project Grants; Research Proposals; Resources; Scientist; Secure; Sex Education; Source; South Korea; Street Drugs; Structure; Students; Subgroup; Talents; Testing; Thick; Time; Toxic effect; United States; University Hospitals; Urine; Work; cohort; cost; critical period; density; design; early onset; follow-up; frontal lobe; gray matter; high school; improved; interest; longitudinal design; meetings; methamphetamine abuse; methamphetamine exposure; neurochemistry; neuroimaging; neuropsychological; neurotoxicity; programs; resilience; treatment strategy; trend; white matter; young adult

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.

描述（由申请人提供）：甲基苯丙胺（MA）是美国增长最快的街头药物。大约有1040万或4.3％的美国人口在他们一生中使用MA。此外，报告了6.2％的高中生在生活中的某个时候使用MA。在韩国，MA滥用一直是数十年来最普遍的毒品滥用形式。成人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潜在的戒酒恢复。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，具体取决于暴露的特定时间。我们的飞行员数据表明​​，青春期的虐待者（13-18岁）的前额叶灰质稀疏，并且这种赤字与发病年龄成反比。在当前的提案中，我们将使用脑磁共振成像扫描进行皮质厚度分析，扩散量张量成像，以评估白质完整性和磁共振光谱范围来量化神经元通过量化神经元的能力。我们的纵向设计可能会提供有关“ MA诱导的神经毒性的固定，进行或弹性课程”和“ MA对发育中大脑的影响”的信息。其次，这种多模式成像设计将为MA诱导的结构和功能性脑缺陷提供深入的知识。第三，纵向和多模式成像设计的结合提供了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依赖的青少年相对于对照组的前额叶缺陷，2）早期发作的青少年MA使用者的前额外缺陷将比晚期发作更大，而3）只有在早期的戒酒中才能恢复，但不会在早期的MA疗程中观察到。探索性分析还将评估1）MA诱导的神经毒性与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综合作用。我们认为，这项研究建议对计划公告中的国际药物成瘾研究（PA-07-275）有着强烈的反应，该研究鼓励利用在国外存在的独特机会，并强调确保外国匹配资金。正如2007年杰出的国际科学家奖给我们团队所承认的那样，我们的有效合作将有助于更好地理解MA滥用对发展中大脑的影响，这将有助于制定更有效的预防和治疗策略，以了解美国增长最快的街头药物。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研究将有助于更好地理解MA滥用对青春期发展大脑的影响。特别是，我们希望评估青春期的MA使用是否与额叶结构和功能的长期不利影响有关。这些知识将有助于为美国增长最快的街头药物制定更有效的预防和治疗策略。