Evidence of Altered Monoamine Oxidase B, an Astroglia Marker, in Early Psychosis with Cannabis Use
Author:
Aji Kankana Nisha1, Lalang Nittha1, Ramos-Jiménez Christian2ORCID, rahimian Reza3ORCID, Mechawar Naguib4ORCID, Turecki Gustavo4ORCID, Chartrand Daniel5, Boileau Isabelle6ORCID, Meyer Jeffrey1ORCID, Rusjan Pablo2ORCID, Mizrahi Romina2ORCID
Affiliation:
1. Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada 2. Clinical and Translational Sciences Lab, Douglas Research Centre, Montreal, Quebec, Canada 3. Douglas Mental Health University Institute, McGill Group for Suicide Studies, Verdun, Quebec, Canada 4. Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada 5. Department of Anesthesia, McGill University, Montreal, Quebec, Canada 6. Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
Abstract
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.
Publisher
Research Square Platform LLC
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