1Neuropediatric Unit, Shaare Zedek Medical Center, 12 Bayit Street, 91031 Jerusalem, Israel.
2Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Mol Autism. 2019 Jan 30;10:2. doi: 10.1186/s13229-019-0256-6. eCollection 2019.
The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet.
Serum levels of the main endocannabinoids, arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), -palmitoylethanolamine (PEA), and -oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2).
Children with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons.
We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD.
内源性大麻素系统（ECS）是突触可塑性和神经调制的主要调节剂。在几种自闭症谱系障碍（ASD）的动物模型中已经证明了 ECS 的改变。在这些模型中的一些中，激活 ECS 挽救了社交缺陷。在人类 ASD 中出现了 ECS 失调的证据，但尚未报告全面评估和与疾病特征的相关性。
通过液相色谱/串联质谱法分析了 93 名 ASD 儿童（年龄=13.1±4.1，范围 6-21；79%为男孩）和 93 名年龄和性别匹配的神经典型儿童（年龄=11.8±4.3，范围 5.5-21；79%为男孩）血清中主要内源性大麻素（AEA 或大麻酰胺）和 2-花生四烯酸甘油（2-AG）及其相关内源性化合物（AA）、-棕榈酰乙醇胺（PEA）和 -油酸乙醇胺（OEA）的水平。结果与性别和药物使用相关，并与 ASD 参与者的年龄、BMI 和适应功能相关，如自闭症诊断观察量表（ADOS-2）、文兰适应行为量表-II（VABS-II）和社会反应量表-II（SRS-2）的评分反映。
与 ASD 儿童相比，血清 AEA（0.722±0.045 对 1.252±0.072，<0.0001，效应大小 0.91）、OEA（17.3±0.80 对 27.8±1.44，<0.0001，效应大小 0.94）和 PEA（4.93±0.32 对 7.15±0.37，<0.0001，效应大小 0.65）水平较低（pmol/mL，平均值±SEM），但 AA 和 2-AG 水平没有差异。AEA、OEA 和 PEA 的血清水平与年龄、性别、BMI、药物和 ASD 参与者的适应功能无显著相关性或相关性。在 ASD 儿童中，但不在对照组中，年龄较小和 BMI 较低与 AEA 水平较低相关。然而，在进行多次比较校正后，这些相关性没有统计学意义。
我们发现 ASD 儿童的血清 AEA、PEA 和 OEA 水平较低。需要进一步的研究来确定循环内源性大麻素水平是否可以用作分层生物标志物，以识别自闭症谱系内具有临床意义的亚组，以及它们是否反映了动物模型中发现的 ASD 中较低的内源性大麻素“张力”。
