Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study
Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study
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DOI：
10.1016/j.drugalcdep.2003.07.001
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发表时间：
2003-12-11
影响因子：
4.2
通讯作者：
Renshaw, PF
中科院分区：
文献类型：
--
作者：
Cowan, RL;Lyoo, IK;Renshaw, PF
广受欢迎的娱乐药物3，4-亚甲基二氧基甲基苯丙胺(MDMA)的作用部分是通过阻断5-羟色胺和多巴胺再摄取来实现的。许多动物和人体研究表明，服用MDMA后，中枢神经系统(CNS)5-羟色胺功能的指标会长期下降。5-羟色胺功能在中枢神经系统中的一个新出现的作用是通过刺激细胞内信号通路和营养因子发挥积极的营养作用。我们假设，人类MDMA使用者可能由于失去了阴囊对皮质细胞的营养作用而表现出新皮质灰质减少。然而，与动物模型不同的是，世界各地的大多数人类MDMA使用者都是多药使用者，因此使这一群体中MDMA毒性的评估复杂化。使用基于体素的形态计量学(VBM)比较了31名MDMA吸毒者和29名非MDMA吸毒者的结构磁共振成像(MRI)扫描，以评估大脑局部灰质和白质的浓度。VBM使用灰质/白质分割和统计参数映射(SPM)分析来计算区域灰质或白质浓度的体素比较。使用这种方法，我们一致地发现，在MDMA吸毒者中，有几个大脑区域的灰质浓度降低。这些区域位于双侧Brodmann区(BA)18、左侧BA 21和左侧BA 45的新皮质，以及双侧小脑和中线脑干。总体而言，这些初步发现表明，MDMA吸毒者有多个灰质减少区域，这可能是先前报道的MDMA吸毒者神经精神障碍的原因。为了进一步解释这些发现，还需要对MDMA和MDMA-多药联合毒性的中枢神经系统影响进行更多的动物模型和人体研究。我们的结果可能的解释包括：易使用MDMA多种药物的预先存在的大脑差异，MDMA和多种药物的直接毒性，MDMA和多种药物毒性的间接变化，或所有这些因素的组合。(C)2003爱思唯尔爱尔兰有限公司。保留所有权利。
The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts its actions in part via blockade of serotonin and dopamine reuptake. Many animal and human studies have demonstrated long-lasting reductions in measures of central nervous system (CNS) serotonin function following MDMA administration. One emerging role of serotonin function in the CNS is a positive trophic effect via stimulation of intracellular signaling pathways and trophic factors. We hypothesized that human MDMA users might display neocortical gray matter reductions due to loss of scrotonergically mediated trophic effects on cortical cells. However, unlike animal models, most human MDMA users worldwide are polydrug users, thereby complicating the assessment of MDMA toxicity in this group. Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM) to assess regional brain gray and white matter concentration. VBM employs gray/white matter segmentation and statistical parametric mapping (SPM) analysis to calculate a voxel-wise comparison of regional gray or white matter concentration. Using this method, we consistently found several brain regions having decreased gray matter concentration in MDMA polydrug users. These regions were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall, these preliminary findings suggest that MDMA polydrug users have multiple regions of gray matter reduction, potentially accounting for previously reported neuropsychiatric impairments in MDMA users. Additional animal model and human studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed to further explain these findings. Potential explanations for our results including pre-existing brain differences predisposing to MDMA polydrug use, direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug toxicity, or combinations of all these factors. (C) 2003 Elsevier Ireland Ltd. All rights reserved.