Brain serotonin transporter density and aggression in abstinent methamphetamine abusers
Brain serotonin transporter density and aggression in abstinent methamphetamine abusers
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DOI：
10.1001/archpsyc.63.1.90
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Mori, N
中科院分区：
文献类型：
--
作者：
Sekine, Y;Ouchi, Y;Mori, N
背景：在动物中，已知甲基苯丙胺对血清素神经元有神经毒性作用，血清素神经元与情绪、焦虑和攻击性的调节有关。目前尚不清楚甲基苯丙胺是否会损害人体的血清素神经元。目的：探讨目前戒断的甲基苯丙胺滥用者脑血清素神经元的状态及其与临床特征的可能关系。设计：病例-对照分析。环境：医院研究中心。参与者：从社区招募的12名目前戒断的前甲基苯丙胺滥用者（5名女性和7名男性）和12名年龄、性别和教育程度相匹配的对照受试者。干预措施：使用正电子发射断层扫描和反式- 1,2,3,5,6,10- β -六氢-6-[4-（甲基硫）苯基]吡咯-[2,1-a]异喹啉（[C-11](+)McN5652）估计了5 -羟色胺转运体（5 -羟色胺神经元的结构成分）的脑区域密度。估计来自感兴趣的区域和统计参数映射方法，然后使用临床变量的测量进行病例内分析。主要结局指标：甲基苯丙胺使用持续时间、攻击和抑郁症状程度、以[C-11] (+)McN-5652分布体积为代表的血清素转运体密度变化。结果：与对照组相比，甲基苯丙胺滥用者表现出更高的攻击性。兴趣区和统计参数映射分析显示，甲基安非他命滥用者的大脑区域（如中脑、丘脑、尾状核、壳核、大脑皮层和小脑）的血清素转运体密度显著低于对照组，且这种降低与甲基安非他命使用时间呈显著负相关。此外，统计参数映射分析表明，眼窝额叶区、颞叶区和前扣带区的密度与甲基苯丙胺滥用者的攻击程度密切相关。结论：长期滥用甲基苯丙胺可能会降低大脑中血清素转运体的密度，导致攻击性升高，即使在目前戒断的滥用者中也是如此。
Context: In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans.Objective: To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers.Design: Case-control analysis.Setting: A hospital research center.Participants: Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community.Interventions: The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans- 1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio) phenyl]pyrrolo-[2,1-a]isoquinoline ([C-11](+)McN5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables.Main Outcomes Measures: The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [C-11] (+)McN-5652 distribution volume.Results: Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers.Conclusions: Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.