背景:重度抑郁症(MDD)和酒精使用障碍(AUD)是两种高度流行的疾病,其中内源性大麻素系统(ECS)被认为起着重要作用。ECS调节两种疾病中不同神经递质的相互作用,这对于控制情绪和对压力和奖励刺激的反应至关重要。测量人血清和血浆中的外周内源性大麻素(eCBs)可以帮助克服检测脑中内源性大麻素水平的局限性。本系统评价旨在确定MDD和/或AUD患者的外周eCBs水平,并找到用于诊断的eCBs。预后生物标志物,和潜在的治疗目标。
方法:从最早的手稿到2023年10月22日,我们根据系统审查和荟萃分析(PRISMA)指南的首选报告项目在三个电子数据库中进行了系统的文献检索。我们纳入了目前诊断为AUD和/或MDD的成年人的研究,并评估了血浆或血清内源性大麻素。我们仔细考虑了可能影响内源性大麻素水平的已知变量。
结果:我们在这篇系统综述中纳入了17篇文章,测量了170名AUD和359名MDD患者的外周eCBs。压力源增加外周2-花生四酰甘油(2-AG)浓度,和2-AG可能是抑郁症严重程度和慢性的特定特征。焦虑症状与anandamide(AEA)浓度呈负相关,AEA在AUD早期禁欲期间显着增加。研究表明,AUD患者的油酰乙醇胺(OEA)与禁欲时间呈负相关。它们还显示AEA和OEA的外周水平与脂肪酸酰胺水解酶(FAAH)活性之间的显著负相关。二十碳五烯醇胺(EPEA)与抑郁症的临床缓解率相关。纳入的研究显示已知的变量,如性别,慢性,症状严重程度,精神病症状并存,在AUD的情况下禁欲的长度,和可影响外周eCB的应激诱导性。
结论:本系统综述强调了ECS在MDD和AUD中的重要作用。外周eCB似乎是这些疾病的有用生物标志物,进一步的研究可能会确定潜在的治疗靶点。在精心设计的临床研究中使用可获得的生物样品如血液对于开发针对这些疾病的新疗法至关重要。
BACKGROUND: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are two high-prevalent conditions where the Endocannabinoid system (ECS) is believed to play an important role. The ECS regulates how different neurotransmitters interact in both disorders, which is crucial for controlling emotions and responses to stress and reward stimuli. Measuring peripheral endocannabinoids (eCBs) in human serum and plasma can help overcome the limitations of detecting endocannabinoid levels in the brain. This systematic review aims to identify levels of peripheral eCBs in patients with MDD and/or AUD and find eCBs to use as diagnostic, prognostic biomarkers, and potential therapeutic targets.
METHODS: We conducted a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines from the earliest manuscript until October 22, 2023, in three electronic databases. We included studies of human adults who had a current diagnosis of AUD and/or MDD and evaluated plasma or serum endocannabinoids. We carefully considered known variables that may affect endocannabinoid levels.
RESULTS: We included 17 articles in this systematic review, which measured peripheral eCBs in 170 AUD and 359 MDD patients. Stressors increase peripheral 2-arachidonyl-glycerol (2-AG) concentrations, and 2-AG may be a particular feature of depression severity and chronicity. Anxiety symptoms are negatively correlated with anandamide (AEA) concentrations, and AEA significantly increases during early abstinence in AUD. Studies suggest a negative correlation between Oleoylethanolamide (OEA) and length of abstinence in AUD patients. They also show a significant negative correlation between peripheral levels of AEA and OEA and fatty acid amide hydrolase (FAAH) activity. Eicosapentaenoylethanolamide (EPEA) is correlated to clinical remission rates in depression. Included studies show known variables such as gender, chronicity, symptom severity, comorbid psychiatric symptoms, length of abstinence in the case of AUD, and stress-inducibility that can affect peripheral eCBs.
CONCLUSIONS: This systematic review highlights the important role that the ECS plays in MDD and AUD. Peripheral eCBs appear to be useful biomarkers for these disorders, and further research may identify potential therapeutic targets. Using accessible biological samples such as blood in well-designed clinical studies is crucial to develop novel therapies for these disorders.