Evidence of Altered Monoamine Oxidase B, an Astroglia Marker, in Early Psychosis with Cannabis Use

Abstract A novel radiotracer, [11C]SL25.1188 targets monoamine oxidase-B (MAO-B) enzyme, which metabolizes monoamines (including dopamine) primarily found in astrocytes. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. However, this has never been tested in living brains of early psychosis. Thirty-eight participants including antipsychotic-free/minimally exposed patients with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-minute positron emission tomography (PET) scan with [11C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.46) = 4.56, p = 0.02, Cohen’s f = 0.49), controlling for tobacco (F (1,37.46) = 5.50 p = 0.02) and cannabis use (F(1,37.46) = 5.05, p = 0.03) with significant reductions in CHR compared to HV (Cohen’s d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.47) = 12.45, p = 0.001, Cohen’s f = 0.56), with a significant group-by-cannabis interaction (F(2,37.35) = 3.81, p = 0.03, Cohen’s f = 0.45), indicating lower MAO-B VT in cannabis-using patients. Decreased MAO-B VT levels was more robust in striatal than cortical regions, in both clinical groups (F(12,46.07) = 2.00, p = 0.046, Cohen’s f = 0.72) and in cannabis users (F(6,46.07) = 6.01, p < 0.001, Cohen’s f = 0.89). Reduced MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP patients. Reduced MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.