Serotonin transporter loss and psychotic state in methamphetamine users

背景：在动物中，已知甲基苯丙胺对血清素神经元具有神经趋近作用，血清素神经元与情绪、焦虑和攻击性的调节有关。然而，目前尚不清楚甲基苯丙胺是否会损害人类的血清素神经元。目的：探讨戒断前甲基苯丙胺滥用者脑5 -羟色胺神经元的状态及其与临床特征的关系。设计：利用正电子发射断层扫描（PET）和[^<11>C](+)McN-5652估计了5 -羟色胺转运体（5 -羟色胺神经元的结构成分）在大脑中的区域密度。通过感兴趣区域（ROI）和统计参数映射（SPM）方法得出的估计值进行病例对照分析，然后通过临床变量测量进行病例内分析。环境：参与者从社区招募到医院研究中心。参与者：12名目前或更多的前甲基苯丙胺滥用者（5名女性，7名男性）和12名年龄、性别匹配的健康对照者（5名女性，7名男性）。主要观察指标：甲基苯丙胺使用时间、攻击程度和抑郁症状、血清素转运体密度变化（以[^<11>C](+)McN-5652分布体积表示）。结果：甲基苯丙胺滥用者的攻击性水平明显高于对照组。ROI和SPM分析均显示，与对照组相比，甲基苯丙胺滥用者大脑各区域（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降低，且这种降低与甲基苯丙胺使用时间呈显著负相关。此外，SPM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，即使在目前处于戒断状态的人群中也是如此。少

Background : In animals, methamphetamine is known to have a neurotaxic effect on seroronin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. However, it remains unknown whether or not 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 former methamphetamine abusers.Desigh : The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated in the brain using positron emission tomography (PET) and [^<11>C](+)McN-5652. A case-control analysis was performed with the estimates derived from region-of-interest (ROI) and statistical parametric mapping (SPM) methods, followed by within-case analysis with the measures of clinical variables.Setting : Partieipants were recruited from the community to a hospital research center.Participants : Twelve currently abst … More inent former methamphetamine abusers (5 women, 7 men) and age-, gender-, and twelve education-matched healthy control subjects (5 women, 7 men).Main Outcome Measures : The duration of methamphetamine use, magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [^<11>C](+)McN-5652 distribution volume.Results : The methamphetamine abusers showed increased levels of aggression compared to those of the control subjects. Both ROI and SPM analyses revealed that the serotonin transporter density in global brain regions (eg, midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in the methamphetamine abusers than in the control subjects, and this reduction was found to be significantly inversely correlated with the duration of methamphetamine use. Furthermore, SPM 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 among those in a currently abstinent state. Less