Brain Functional Correlates of MDMA Use in Adolescence

青春期 MDMA 使用的脑功能相关性

• 批准号: 7488985
• 负责人: LESLIE K JACOBSEN
• 金额: $ 28.74万
• 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 2008-09-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488985
• 关键词: Abstinence; Adolescence; Adolescent; Adult; Age; Animals; Attention; Brain; Cannabis; Cerebrospinal Fluid; Cerebrum; Classification; Cognition; Cognitive; Cognitive deficits; Control Groups; Data; Development; Developmental Process; Disruption; Dose; Drug usage; Functional Imaging; Functional Magnetic Resonance Imaging; Gender; Goals; Hippocampus (Brain); Hydroxyindoleacetic Acid; Impairment; Inferior; Laboratories; Left; Longitudinal Studies; Magnetic Resonance Imaging; Mediating; Nature; Neurons; Numbers; Organizational Change; Parietal; Pattern; Performance; Pharmaceutical Preparations; Pilot Projects; Principal Investigator; Publishing; Reaction Time; Recording of previous events; Relative (related person); Scanning; Serotonin; Short-Term Memory; Task Performances; Teenagers; Testing; Tobacco; Tobacco use; Vulnerable Populations; cognitive function; density; design; ecstasy; experience; follow-up; human study; improved; memory recognition; motivational enhancement therapy; neural circuit; neurotoxic; polysubstance abuse; processing speed; programs; research study; therapy design

The primary goal of this proposal 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 subj ects during performance of a working memory task shows altered frontal and hippocampal function during high working memory load. The present proposal 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.

该提案的主要目的是评估认知缺陷的存在和性质 具有MDMA史（“摇头丸”）使用的青少年，用于测试脑功能的相关变化，并 确定认知缺陷是否随着MDMA的持续戒酒而改善。 在动物中，MDMA对皮质和皮质下血清素​​能神经元的持续损害甚至 当以休闲剂量服用时。成年人类MDMA使用者的标记密度降低 脑血清素能神经元，脑脊髓液（CSF）降低5-羟色胺代谢产物5-- 羟基丁乙酸（5-HIAA），以及立即和延迟召回的损害，执行认知 功能和反应时间。 在青少年中，MDMA的娱乐性使用仍然很重要。但是，认知和大脑 青少年使用MDMA使用的功能相关性仍未探索。此外，大脑的程度 与青春期期间与MDMA使用相关的功能变化尚不清楚。这样的 迫切需要信息来指导临床医生和教育工作者进行治疗和教育的设计 计划满足这一脆弱人群的需求。 来自青少年MDMA用户的认知和大脑功能的试点研究的初步数据 在我们的实验室中进行的表明，青少年MDMA使用者在测试中的反应时间延长 延迟识别记忆中的选择性和分裂的注意力和缺陷。功能磁性 共振成像（fMRI）数据在执行工作记忆任务期间从这些子手段收集 显示在高工作记忆负载期间的额叶和海马功能变化。 本提案将采用纵向设计来测试青春期使用MDMA是否是 与与大麻或烟草使用相关的缺陷之外的认知缺陷相关，以及是否存在 这些缺陷随着MDMA的持续戒酒而改善。另外，MDMA是否在 青春期与介导工作性能的神经回路功能的改变有关 将检查记忆以及选择性和分裂的注意任务。最后，我们将测试MDMA-是否 海马功能的相关变化可预测延迟的召回或识别记忆的减少和 MDMA相关的功能变化是否介导选择性和分裂注意力预测 这些任务执行过程中处理速度降低。