BACKGROUND The brain's endocannabinoid system, the primary target of cannabis, has been implicated in psychosis. The endocannabinoid anandamide is elevated in cerebrospinal fluid of patients with schizophrenia. Fatty acid amide hydrolase (FAAH) controls brain anandamide levels; however, it is unknown if FAAH is altered in vivo in psychosis or related to positive psychotic symptoms. METHODS Twenty-seven patients with schizophrenia spectrum disorders and 36 healthy control subjects completed high-resolution positron emission tomography scans with the novel FAAH radioligand [11C]CURB and structural magnetic resonance imaging. Data were analyzed using the validated irreversible 2-tissue compartment model with a metabolite-corrected arterial input function. RESULTS FAAH did not differ significantly between patients with psychotic disorders and healthy control subjects (F1,62.85 = 0.48, p = .49). In contrast, lower FAAH predicted greater positive psychotic symptom severity, with the strongest effect observed for the positive symptom dimension, which includes suspiciousness, delusions, unusual thought content, and hallucinations (F1,26.69 = 12.42, p = .002; Cohen's f = 0.42, large effect). Shorter duration of illness (F1,26.95 = 13.78, p = .001; Cohen's f = 0.39, medium to large effect) and duration of untreated psychosis predicted lower FAAH (F1,26.95 = 6.03, p = .021, Cohen's f = 0.27, medium effect). These results were not explained by past cannabis exposure or current intake of antipsychotic medications. FAAH exhibited marked differences across brain regions (F7,112.62 = 175.85, p < 1 × 10-56; Cohen's f > 1). Overall, FAAH was higher in female subjects than in male subjects (F1,62.84 = 10.05, p = .002; Cohen's f = 0.37). CONCLUSIONS This first study of brain FAAH in psychosis indicates that FAAH may represent a biomarker of disease state of potential utility for clinical studies targeting psychotic symptoms or as a novel target for interventions to treat psychotic symptoms.

中文翻译：

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未经治疗的精神病患者的脑脂肪酸酰胺水解酶成像

背景技术大脑的内源性大麻素系统是大麻的主要目标，与精神病有关。精神分裂症患者脑脊液中的内源性大麻素 anandamide 升高。脂肪酸酰胺水解酶 (FAAH) 控制大脑 anandamide 水平；然而，尚不清楚 FAAH 是否在精神病体内发生改变或与阳性精神病症状有关。方法 27 名精神分裂症谱系障碍患者和 36 名健康对照受试者使用新型 FAAH 放射性配体 [11C] CURB 和结构磁共振成像完成了高分辨率正电子发射断层扫描。使用经过验证的不可逆 2 组织隔室模型分析数据，该模型具有代谢物校正的动脉输入功能。结果 FAAH 在精神病患者和健康对照受试者之间没有显着差异（F1,62.85 = 0.48, p = .49）。相比之下，较低的 FAAH 预示着更严重的阳性精神病症状，阳性症状维度的影响最强，包括怀疑、妄想、不寻常的思想内容和幻觉（F1，26.69 = 12.42，p = .002；Cohen's f = 0.42，大效应）。较短的疾病持续时间（F1,26.95 = 13.78, p = .001; Cohen's f = 0.39, 中到大效应）和未经治疗的精神病持续时间预测较低的 FAAH（F1,26.95 = 6.03, p = .021, Cohen's f = 0.27 ，中等效果）。这些结果不能用过去的大麻暴露或目前服用的抗精神病药物来解释。FAAH 在大脑区域表现出显着差异 (F7,112.62 = 175.85, p < 1×10-56；科恩的 f > 1)。总体而言，女性受试者的 FAAH 高于男性受试者 (F1,62.84 = 10.05, p = .002; Cohen's f = 0.37)。结论 第一项关于精神病患者脑 FAAH 的研究表明，FAAH 可能代表疾病状态的生物标志物，可用于针对精神病症状的临床研究或作为治疗精神病症状的干预的新目标。