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具有MDMA史（“狂喜”）使用史的青少年认知缺陷的存在和性质，以测试大脑功能的相关变化，并确定认知缺陷是否会随着MDMA的持续戒烟而改善认知缺陷。 在动物中，即使在休闲剂量服用时，MDMA也会对皮质和皮质下血清素​​能神经元产生长期损害。成年人类MDMA使用者的脑血清素能神经元标记的密度降低，脑脊髓液（CSF）降低了5-羟色胺代谢产物5-羟基内丁乙酸（5-HIAA）的浓度，以及直接和延迟的召回，执行认知功能和反应时间和反应时间和反应时间和反应时间。 在青少年中，MDMA的娱乐使用仍然很重要。但是，青少年使用MDMA使用的认知和脑功能相关性仍未得到探索。此外，尚不清楚与青春期期间与MDMA使用相关的大脑功能变化的程度。迫切需要进行此类信息，以指导临床医生和教育工作者的治疗和教育计划，以满足这一脆弱人群的需求。 来自我们实验室中进行的青少年MDMA使用者的认知和大脑功能的初步数据表明，在选择性和分裂的注意力和划分延迟识别记忆中的注意力和缺陷期间，青少年MDMA使用者的反应时间延长。在工作记忆任务执行期间，从这些受试者收集的功能磁共振成像（fMRI）数据显示，在高工作记忆负载期间，额叶和海马功能发生了变化。 本应用将采用纵向设计来测试青春期使用MDMA是否与与大麻或烟草使用相关的缺陷之外的认知缺陷有关，以及这些缺陷是否随着MDMA持续戒酒而改善。此外，将检查青春期使用MDMA是否与介导工作记忆以及选择性和分裂注意任务的神经回路功能的改变有关。最后，我们将测试MDMA与海马功能的相关变化是否可以预测延迟召回或识别记忆的减少，以及在介导选择性和分裂注意力的神经电路中与MDMA相关的功能变化是否预测了这些任务执行过程中处理速度的降低。