Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use.

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-10-01 DOI:10.1093/ijnp/pyae044

Emily R Weiss, Margaret T Davis, Ruth H Asch, Deepak Cyril D'Souza, Ryan Cool, Irina Esterlis

{"title":"Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use.","authors":"Emily R Weiss, Margaret T Davis, Ruth H Asch, Deepak Cyril D'Souza, Ryan Cool, Irina Esterlis","doi":"10.1093/ijnp/pyae044","DOIUrl":null,"url":null,"abstract":"Background: Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology.Methods: Using positron emission tomography with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology (n = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, hippocampus) differed as a function of CU status.Results: Past-year CU (n = 22) was associated with 18.62%-19.12% higher mGlu5 availability in frontal and 14.24%-16.55% higher mGlu5 in limbic ROIs relative to participants with no recent CU. Similarly, past-month or monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05%-20.62%) and limbic (15.53%-16.83%) ROIs. mGlu5 availability in the orbitofrontal cortex and amygdala was negatively associated with depressive symptoms in the past-year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs and with perceptions of worthlessness and past failures (r's = -.47 to .66, P's = .006-.033) in the ventromedial prefrontal cortex. Participants with CU reported lower mean depressive symptoms (P's = .006-.037) relative to those without CU.Conclusions: These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ijnp/pyae044","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology.

Methods: Using positron emission tomography with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology (n = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, hippocampus) differed as a function of CU status.

Results: Past-year CU (n = 22) was associated with 18.62%-19.12% higher mGlu5 availability in frontal and 14.24%-16.55% higher mGlu5 in limbic ROIs relative to participants with no recent CU. Similarly, past-month or monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05%-20.62%) and limbic (15.53%-16.83%) ROIs. mGlu5 availability in the orbitofrontal cortex and amygdala was negatively associated with depressive symptoms in the past-year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs and with perceptions of worthlessness and past failures (r's = -.47 to .66, P's = .006-.033) in the ventromedial prefrontal cortex. Participants with CU reported lower mean depressive symptoms (P's = .006-.037) relative to those without CU.

Conclusions: These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Metabotropic glutamatergic receptor 5 作为创伤与吸食大麻交汇的潜在生物标志物。

背景：代谢谷氨酸受体 5（mGlu5）失调被认为与创伤相关精神病理学的病理生理学有关，而且内源性大麻素与谷氨酸能系统之间存在直接的相互作用。然而，在创伤相关精神病理学中，大麻使用（CU）与 mGlu5 之间的关系尚未得到直接研究：方法：我们使用[18F]FPEB正电子发射断层扫描（PET），在创伤相关精神病理学交叉诊断样本（N = 55）中研究了CU状态与体内mGlu5可用性之间的关系。具体来说，我们测试了前边缘感兴趣区（ROIs；dlPFC、OFC、vmPFC、杏仁核、海马）的mGlu5可用性是否随CU状态而变化：与近期没有CU的参与者相比，过去一年的CU（n = 22）与额叶和边缘ROI的mGlu5可用性分别高出18.97%-19.12%和14.24%-16.55%有关。同样，过去一个月/每月的 CU（n = 16）与额叶（18.05-20.62%）和边缘（15.53-16.83%）ROI 中较高的 mGlu5 可用性相关。在两个CU组中，探索性分析表明，在所有ROI中，mGlu5可用性与悲伤情绪呈负相关，在vmPFC中，mGlu5可用性与无价值感和过去的失败呈负相关（r's = -.46-.66，p's = .006-.033）。与没有CU的参与者相比，有CU的参与者报告的抑郁症状平均值较低（p's = .019-.031）：这些发现对我们理解 CU 与谷氨酸能神经递质之间在创伤相关精神病理学中的相互作用具有重要意义，并强调了在制定治疗方案时需要考虑 CU 对这一人群的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

International Journal of Neuropsychopharmacology 医学-精神病学

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.