大脑 mGlu5 与认知和吸烟有关,但在长期吸食甲基苯丙胺的早期戒断中与对照组没有差异。

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-08-01 DOI:10.1093/ijnp/pyae031
Megan N McClintick, Robert M Kessler, Mark A Mandelkern, Tarannom Mahmoudie, Daicia C Allen, Hilary Lachoff, Jean-Baptiste F Pochon, Dara G Ghahremani, Judah B Farahi, Edwin Partiai, Robert A Casillas, Larissa J Mooney, Andy C Dean, Edythe D London
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引用次数: 0

摘要

背景:I组代谢谷氨酸受体亚型五(mGlu5)与动物甲基苯丙胺暴露和人类认知有关。由于甲基苯丙胺使用障碍(MUD)患者表现出认知缺陷,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关联:正电子发射断层扫描测量了 mGlu5 的放射性示踪剂 [18F]FPEB 在 MUD 患者(戒断甲基苯丙胺至少两周,n = 14)和对照组(n = 14)大脑中的总分布容积(VT)。研究人员还进行了吸毒史问卷调查以及言语学习、空间工作记忆和执行功能测试。测试了 VT 与甲基苯丙胺使用、烟草使用和认知能力的关联:结果:MUD 参与者在整体或区域 VT 方面与对照组没有差异,甲基苯丙胺使用情况与 VT 没有相关性。与吸烟者相比,不吸烟者的VT明显高于吸烟者(主效应,p = 0.0041)。与对照组相比,MUD 参与者在雷伊听觉言语学习任务(RAVLT)和 Stroop 测试(分别为 p = 0.08 和 p = 0.13)上表现出不明显的弱点,效应大小为中等到较大,而在 SCAP 上的表现则明显低于对照组(p = 0.015)。在各组中,RAVLT表现与背外侧前额叶皮层(DLPFC)和额上回的VT相关:结论:禁欲 MUD 患者的大脑中没有 mGlu5 下调的证据,但 dlPFC 中的 VT 与言语学习相关,这表明针对 mGlu5 的药物可能会改善认知能力。
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Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

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.

Conclusion: 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.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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