Brain Functional Correlates of MDMA Use in Adolescence

青春期 MDMA 使用的脑功能相关性

• 批准号: 6953618
• 负责人: LESLIE K JACOBSEN
• 金额: $ 39.07万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6953618
• 关键词: 3,4 methylenedioxymethamphetamine; adolescence (12-20); attention; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; clinical research; cognition disorders; drug /alcohol abstinence; drug abuse; frontal lobe /cortex; functional magnetic resonance imaging; hippocampus; human subject; hydroxyindoleacetate; longitudinal human study; neural information processing; neurons; pathologic process; patient oriented research; psychomotor reaction time; serotonin; short term memory

DESCRIPTION (provided by applicant): The primary goal of this application is to assess for the presence and nature of cognitive deficits in adolescents with a history of MDMA ("ecstasy") use, to test for correlated changes in brain function, and to determine whether cognitive deficits improve with sustained abstinence from MDMA. In animals MDMA produces long-lasting damage to cortical and subcortical serotonergic neurons even when administered in recreational doses. Adult human MDMA users have reduced density of markers of brain serotonergic neurons, reduced cerebral spinal fluid (CSF) concentrations of the serotonin metabolite 5- hydroxyindoleacetic acid (5-HIAA), and impairments in immediate and delayed recall, executive cognitive function, and reaction time. Recreational use of MDMA remains substantial among adolescents. However, cognitive and brain functional correlates of MDMA use in adolescents remain unexplored. Further, the degree to which brain functional changes associated with MDMA use during adolescence are reversible is not known. Such information is urgently needed to guide clinicians and educators in the design of treatment and educational plans that will meet the needs of this vulnerable population. Preliminary data from a pilot study of cognition and brain function in adolescent MDMA users conducted in our laboratory suggests that adolescent MDMA users have prolonged reaction times during tests of selective and divided attention and deficits in delayed recognition memory. Functional magnetic resonance imaging (fMRI) data collected from these subjects during performance of a working memory task shows altered frontal and hippocampal function during high working memory load. The present application will employ a longitudinal design to test whether MDMA use in adolescence is associated with cognitive deficits beyond those deficits associated with cannabis or tobacco use, and whether these deficits improve with sustained abstinence from MDMA. In addition, whether MDMA use in adolescence is associated with altered function of neural circuits mediating the performance of working memory and selective and divided attention tasks will be examined. Finally, we will test whether MDMA related changes in hippocampal function predict decrements in delayed recall or recognition memory and whether MDMA-related functional changes in neurocircuits mediating selective and divided attention predict reduced speed of processing during performance of these tasks.

描述（由申请人提供）：本申请的主要目标是评估有 MDMA（“摇头丸”）使用史的青少年是否存在认知缺陷及其性质，测试大脑功能的相关变化，并确定持续戒除 MDMA 是否会改善认知缺陷。 在动物中，即使以娱乐剂量服用，MDMA 也会对皮质和皮质下血清素​​神经元产生长期损害。成人 MDMA 使用者大脑血清素能神经元标记密度降低，脑脊液 (CSF) 血清素代谢物 5-羟基吲哚乙酸 (5-HIAA) 浓度降低，即时和延迟回忆、执行认知功能和反应受损时间。 青少年中消遣性使用摇头丸的情况仍然很多。然而，青少年使用摇头丸的认知和大脑功能的相关性仍有待探索。此外，与青春期使用摇头丸相关的大脑功能变化的可逆程度尚不清楚。迫切需要此类信息来指导临床医生和教育工作者设计满足这一弱势群体需求的治疗和教育计划。 我们实验室对青少年摇头丸使用者认知和大脑功能进行的初步研究的初步数据表明，青少年摇头丸使用者在选择性和分散注意力测试以及延迟识别记忆缺陷测试中反应时间延长。在执行工作记忆任务期间从这些受试者收集的功能磁共振成像（fMRI）数据显示，在高工作记忆负荷期间，额叶和海马功能发生了变化。 本申请将采用纵向设计来测试青春期使用 MDMA 是否与除大麻或烟草使用相关缺陷之外的认知缺陷相关，以及这些缺陷是否会随着 MDMA 的持续戒断而改善。此外，还将研究青春期使用摇头丸是否与介导工作记忆以及选择性和分散注意力任务表现的神经回路功能改变有关。最后，我们将测试 MDMA 相关的海马功能变化是否预示着延迟回忆或识别记忆的减少，以及 MDMA 相关的介导选择性和分散注意力的神经回路的功能变化是否预示着执行这些任务期间处理速度的降低。