Schizophrenia Clinic Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.
Neuropsychopharmacology. 2013 Dec;38(13):2568-77. doi: 10.1038/npp.2013.165. Epub 2013 Jul 4.
Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.
几种涉及免疫系统改变的假说被提出作为精神障碍的病因学解释。内源性大麻素系统 (ECS) 作为一种内源性神经保护和抗炎系统具有维持内环境稳定的作用。该系统的改变与精神病有关。大麻的使用是这些疾病的一个强有力的风险因素，它可能改变 ECS 的信号转导。在这项研究中，招募了 95 名首发精神分裂症（FEP）患者和 90 名健康对照者。通过 Western blot 分析测定了外周血单核细胞（PBMC）中大麻素受体 2（CB2）的蛋白表达、主要内源性大麻素合成酶 N-酰基磷脂酰乙醇胺磷酸酶（NAPE）和二酰基甘油脂肪酶（DAGL）的蛋白水平，以及降解酶脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MAGL）。与健康对照组相比，FEP 患者的 CB2 表达以及两种内源性大麻素合成酶（NAPE 和 DAGL）的表达均降低。在控制年龄、性别、体重指数和大麻使用后，NAPE 和 DAGL 的表达仍然显著降低，而 FAAH 和 MAGL 的表达增加。另一方面，与健康对照组相比，有严重大麻使用史的 FEP 患者 ECS 失调更为严重。这些结果表明，FEP 患者 PBMC 中存在 ECS 失调。精神病发病初期 ECS 的改变可能有助于疾病的病理生理学，是精神障碍的一个潜在生物标志物，也是治疗目的值得考虑的一个有趣的药理学靶点。
