PDF(Pubmed)
Abstract：
BACKGROUND: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance.
METHODS: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested.
RESULTS: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus.
CONCLUSIONS: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.
METHODS: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested.
RESULTS: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus.
CONCLUSIONS: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.
摘要：
背景：I组代谢型谷氨酸受体亚型5（mGlu5）与动物的甲基苯丙胺暴露有关，在人类认知中。因为患有甲基苯丙胺使用障碍（MUD）的人表现出认知缺陷，我们评估了MUD患者和对照组的mGlu5，并测试了其与认知表现的相关性。
方法：进行正电子发射断层扫描以测量[18F]FPEB的总分布体积（VT），mGlu5的放射性示踪剂，在MUD参与者的大脑中(戒除甲基苯丙胺至少两周，n=14）和对照组（n=14）。药物使用史问卷和口头学习测试，空间工作记忆，和执行功能进行管理。VT与甲基苯丙胺使用的关联，烟草使用,和认知表现进行了测试。
结果：MUD参与者在全球或区域VT中与对照组没有差异，甲基苯丙胺使用的测量值与VT无关。在全球范围内，非吸烟人群的VT明显高于非吸烟人群。吸烟参与者(主要影响，p=0.0041)。MUD参与者在Rey听觉语言学习任务（RAVLT）和Stroop测试与具有中等至较大效应大小的对照(分别为p=0.08和p=0.13)，并且显著低于SCAP的控制(p=0.015)。跨群体,RAVLT表现与背外侧前额叶皮层（DLPFC）和额上回的VT相关。
结论：无证据表明MUD患者脑中mGlu5下调，但是dlPFC中的VT与言语学习的关联表明,靶向mGlu5的药物可能会改善认知能力.
方法：进行正电子发射断层扫描以测量[18F]FPEB的总分布体积（VT），mGlu5的放射性示踪剂，在MUD参与者的大脑中(戒除甲基苯丙胺至少两周，n=14）和对照组（n=14）。药物使用史问卷和口头学习测试，空间工作记忆，和执行功能进行管理。VT与甲基苯丙胺使用的关联，烟草使用,和认知表现进行了测试。
结果：MUD参与者在全球或区域VT中与对照组没有差异，甲基苯丙胺使用的测量值与VT无关。在全球范围内，非吸烟人群的VT明显高于非吸烟人群。吸烟参与者(主要影响，p=0.0041)。MUD参与者在Rey听觉语言学习任务（RAVLT）和Stroop测试与具有中等至较大效应大小的对照(分别为p=0.08和p=0.13)，并且显著低于SCAP的控制(p=0.015)。跨群体,RAVLT表现与背外侧前额叶皮层（DLPFC）和额上回的VT相关。
结论：无证据表明MUD患者脑中mGlu5下调，但是dlPFC中的VT与言语学习的关联表明,靶向mGlu5的药物可能会改善认知能力.
