Abstract：
Background: Dysregulation of the endocannabinoid (eCB) system is implicated in various stress-related neuropsychiatric disorders (SRDs), including anxiety, depression, and post-traumatic stress disorder (PTSD). In this systematic review and meta-analysis, our objectives were to characterize circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) concentrations at rest and in response to acute laboratory-based psychosocial stress in individuals with SRDs and without (controls). Our primary aims were to assess the effects of acute psychosocial stress on eCB concentrations in controls (Aim 1), compare baseline (prestress) eCB concentrations between individuals with SRDs and controls (Aim 2), and explore differential eCB responses to acute psychosocial stress in individuals with SRDs compared with controls (Aim 3). Methods: On June 8, 2023, a comprehensive review of the MEDLINE (PubMed) database was conducted to identify original articles meeting inclusion criteria. A total of 1072, 1341, and 400 articles were screened for inclusion in Aims 1, 2, and 3, respectively. Results: Aim 1, comprised of seven studies in controls, revealed that most studies reported stress-related increases in AEA (86%, with 43% reporting statistical significance) and 2-AG (83%, though none were statistically significant except for one study in saliva). However, meta-analyses did not support these patterns (p\'s>0.05). Aim 2, with 20 studies, revealed that most studies reported higher baseline concentrations of both AEA (63%, with 16% reporting statistical significance) and 2-AG (60%, with 10% reporting statistical significance) in individuals with SRDs compared with controls. Meta-analyses confirmed these findings (p\'s<0.05). Aim 3, which included three studies, had only one study that reported statistically different stress-related changes in 2-AG (but not AEA) between individuals with PTSD (decrease) and controls (increase), which was supported by the meta-analysis (p<0.001). Meta-analyses showed heterogeneity across studies and aims (I2=14-97%). Conclusion: Despite substantial heterogeneity in study characteristics, samples, and methodologies, consistent patterns emerged, including elevated baseline AEA and 2-AG in individuals with SRDs compared with controls, as well as smaller stress-related increases in 2-AG in individuals with SRDs compared with controls. To consider eCBs as reliable biomarkers and potential intervention targets for SRDs, standardized research approaches are needed to clarify the complex relationships between eCBs, SRDs, and psychosocial stress.
摘要：
背景：内源性大麻素（eCB）系统的失调与各种压力相关的神经精神疾病（SRD）有关，包括焦虑,抑郁症,和创伤后应激障碍（PTSD）。在这篇系统综述和荟萃分析中，我们的目标是在有和没有SRD的个体(对照)中,在静息时和对急性实验室心理社会应激的反应中,确定循环中的anandamide(AEA)和2-花生四酰基甘油(2-AG)浓度.我们的主要目的是评估急性心理社会应激对对照组eCB浓度的影响（目的1），比较有SRD的个体和对照组之间的基线(预应力)eCB浓度(目标2)，并探讨与对照组相比，SRD患者对急性社会心理应激的eCB反应差异(目标3)。方法：2023年6月8日，对MEDLINE（PubMed）数据库进行全面审查，以识别符合纳入标准的原始文章。共筛选了1072、1341和400篇文章，分别纳入目标1、2和3。结果：目标1，包括七项对照研究，透露，大多数研究报告AEA与压力相关的增加(86%，43%报告有统计学意义)和2-AG(83%，尽管除了一项唾液研究外，没有统计学意义）。然而,荟萃分析不支持这些模式(p>0.05)。目标2，20项研究，揭示了大多数研究报告两种AEA的基线浓度较高(63%，16%报告有统计学意义)和2-AG(60%，与对照组相比，有SRD的个体中有10％报告有统计学意义）。荟萃分析证实了这些发现(p<0.05)。目标3包括三项研究，只有一项研究报告了PTSD（减少）和对照组（增加）之间2-AG（但不是AEA）的压力相关变化的统计学差异，这得到了荟萃分析的支持（p<0.001）。荟萃分析显示不同研究和目标的异质性(I2=14-97%)。结论：尽管研究特征具有很大的异质性，样品,和方法论，一致的模式出现了，包括与对照组相比，SRD患者的基线AEA和2-AG升高，与对照组相比，SRD患者的2-AG压力相关增加较小。为了将eCB视为SRD的可靠生物标志物和潜在干预目标，需要标准化的研究方法来澄清eCB之间的复杂关系，SRDs,和心理社会压力。
