Weidenauer Ana, Garani Ranjini, Lalang Nittha, Watts Jeremy, Lepage Martin, Rusjan Pablo M, Mizrahi Romina
Division of General Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna 1090, Austria.
Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna 1090, Austria.
Schizophr Bull. 2024 Dec 27. doi: 10.1093/schbul/sbae212.
Cognitive impairments are particularly disabling for patients with a psychotic disorder and often persist despite optimization of antipsychotic treatment. Thus, motivating an extension of the research focus on the endocannabinoid system. The aim of this study was to evaluate group differences in brain fatty acid amid hydrolase (FAAH), an endocannabinoid enzyme between first-episode psychosis (FEP), individuals with clinical high risk (CHR) for psychosis and healthy controls (HCs). Furthermore, to test the hypothesis that FAAH is linked with cognition using positron emission tomography (PET).
We analyzed 80 PET scans with the highly selective FAAH radioligand [11C]CURB, including 30 patients with FEP (6 female), 15 CHR (5 female), and 35 HC (19 female). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Berg Card Sorting Test (BCST) were applied to test cognitive performance.
There was no difference in FAAH activity between groups (F2, 75 = 0.75, P = .48; Cohen's f = 0.141; small effect). Overall, there was a difference in the association between groups regarding FAAH activity and the domain visuospatial construction (F2, 72 = 4.67, P = .01; Cohen's f = .36; medium effect). Furthermore, across the sample, lower FAAH activity was associated with a higher percentage of perseverative responses (F1, 66 = 5.06, P = .03; Cohen's f = 0.28, medium effect).
We report evidence for associations between endocannabinoid alterations in FEP and CHR with specific domains of cognition (visuospatial construction and perseverative response), not overall cognition.
认知障碍对于患有精神障碍的患者而言尤其具有致残性，并且即便抗精神病药物治疗已达到最佳状态，这些障碍通常仍会持续存在。因此，这促使人们将研究重点扩展至内源性大麻素系统。本研究的目的是评估首发精神病（FEP）患者、临床高危（CHR）精神病个体和健康对照（HC）之间，脑脂肪酸酰胺水解酶（FAAH，一种内源性大麻素酶）的组间差异。此外，使用正电子发射断层扫描（PET）来检验FAAH与认知相关的假设。
我们使用高选择性FAAH放射性配体[11C]CURB分析了80例PET扫描结果，其中包括30例FEP患者（6例女性）、15例CHR个体（5例女性）和35例HC（19例女性）。应用可重复神经心理状态评估量表（RBANS）和伯格卡片分类测验（BCST）来测试认知表现。
各组之间FAAH活性无差异（F2, 75 = 0.75，P = 0.48；科恩f值 = 0.141；效应量小）。总体而言，各组之间在FAAH活性与视觉空间构建领域的关联方面存在差异（F2, 72 = 4.67，P = 0.01；科恩f值 = 0.36；效应量中等）。此外，在整个样本中，较低的FAAH活性与较高比例的持续性反应相关（F1, 66 = 5.06，P = 0.03；科恩f值 = 0.28，效应量中等）。
我们报告了FEP和CHR中内源性大麻素改变与特定认知领域（视觉空间构建和持续性反应）而非整体认知之间存在关联的证据。
