The Role of Fatty Acid Amide Hydrolase, a Key Regulatory Endocannabinoid Enzyme, in Domain-Specific Cognitive Performance in Psychosis.

Background And Hypothesis: 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).

Study Design: 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.

Study Results: 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).

Conclusions: 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.