Jia Xinlei, Gao Shumin, Liu Xiaotong, Feng Zhendong, Wang Xingxing, Lan Kunyi, Lu Yan'e, Han Lei, Wei Ya Bin, Liu Jia Jia
School of Nursing, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Beijing Key Laboratory of Drug Dependence Reasearch, National Institute On Drug Dependence, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Eur Arch Psychiatry Clin Neurosci. 2025 Jun 15. doi: 10.1007/s00406-025-02031-x.
Dysregulation of the endocannabinoid system (ECS) might be related to autism spectrum disorder (ASD). This study conducts a meta-analysis on the dysregulation of the ECS across ASD animal models and individuals with ASD and systematically reviews the impact of these alterations in ASD animal models. Out of 47 papers assessed for eligibility, 16 animal studies and five human studies were included for narrative synthesis and seven and three for quantitative analysis, respectively. The results revealed a significant decrease in hippocampus anandamide (AEA) levels (SMD = -1.06, 95% CI [-1.78, -0.33], p < 0.01) among ASD animal models and a decrease in blood AEA levels in individuals with ASD (SMD = -0.79, 95% CI [-1.28, -0.30], p = 0.002) compared to normal controls. In the prefrontal cortex, 2-arachidonoylglycerol (2-AG) levels were significantly decreased, despite high heterogeneity between studies (SMD = -1.00, 95% CI [-1.93, -0.06], p = 0.04). No significant changes compared to normal controls were observed in levels of AEA (SMD = -0.48, 95% CI [-1.20, 0.25], p = 0.20), 2-AG (SMD = -0.62, 95% CI [-1.27, 0.02], p = 0.06) in combined brain regions. The narrative synthesis revealed that elevated AEA and 2-AG levels could ameliorate core and associated autistic-like symptoms with region and sex-dependent variations in ASD animal models. Future research should focus on specific mechanisms of endocannabinoids regional effects while considering sex-related influences.
内源性大麻素系统（ECS）失调可能与自闭症谱系障碍（ASD）有关。本研究对ASD动物模型和ASD个体中ECS的失调进行了荟萃分析，并系统回顾了这些改变在ASD动物模型中的影响。在评估是否符合纳入标准的47篇论文中，分别有16项动物研究和5项人体研究被纳入进行叙述性综合分析，7项和3项纳入定量分析。结果显示，与正常对照组相比，ASD动物模型中海马花生四烯酸乙醇胺（AEA）水平显著降低（标准化均数差[SMD]= -1.06，95%可信区间[-1.78, -0.33]，p<0.01），ASD个体血液中AEA水平降低（SMD= -0.79，95%可信区间[-1.28, -0.30]，p=0.002）。在前额叶皮质，尽管研究之间存在高度异质性，但2-花生四烯酸甘油（2-AG）水平显著降低（SMD= -1.00，95%可信区间[-1.93, -0.06]，p=0.04）。在联合脑区中，与正常对照组相比，AEA（SMD= -0.48，95%可信区间[-1.20, 0.25]，p=0.20）、2-AG（SMD= -0.62，95%可信区间[-1.27, 0.02]，p=0.06）水平未观察到显著变化。叙述性综合分析显示，升高的AEA和2-AG水平可改善ASD动物模型中的核心及相关自闭症样症状，且存在区域和性别依赖性差异。未来的研究应在考虑性别相关影响的同时，关注内源性大麻素区域效应的具体机制。
