Silvia Rigucci1,2,3, Lijing Xin4, Paul Klauser1,2, Philipp S Baumann1,2, Luis Alameda1,2, Martine Cleusix2, Raoul Jenni2, Carina Ferrari1, Maurizio Pompili3, Rolf Gruetter5,6,7, Kim Q Do8, Philippe Conus1. 1. TIPP (Treatment and Early Intervention in Psychosis Program); Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland. 2. Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland. 3. Department of Neurosciences, Sensory Organs and Mental Health, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. 4. Animal imaging and technology core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 5. Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 6. Departments of Radiology, University of Lausanne, Lausanne, Switzerland. 7. Department of Radiology, University of Geneva, Geneva, Switzerland. 8. Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland. Kim.Do@chuv.ch.
Abstract
RATIONALE: Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial. OBJECTIVE: We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC). METHODS: Magnetic resonance spectroscopy was used to measure [GlumPFC] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery. RESULTS: [GlumPFC] was lower in EP users comparing to both HC and EP non-users (p < 0.001 and p = 0.01, respectively), while no differences were observed between EP non-users and HC. A greater [GlumPFC]-decline with age was observed in EP users (r = -.46; p = 0.04), but not in EP non-users or HC. Among neuropsychological outcomes, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. CONCLUSIONS: Cannabis use is associated with reduced prefrontal [GlumPFC] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.
RATIONALE: Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressingGlu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophreniapatients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial. OBJECTIVE: We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC). METHODS: Magnetic resonance spectroscopy was used to measure [GlumPFC] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery. RESULTS: [GlumPFC] was lower in EP users comparing to both HC and EP non-users (p < 0.001 and p = 0.01, respectively), while no differences were observed between EP non-users and HC. A greater [GlumPFC]-decline with age was observed in EP users (r = -.46; p = 0.04), but not in EP non-users or HC. Among neuropsychological outcomes, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. CONCLUSIONS: Cannabis use is associated with reduced prefrontal [GlumPFC] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.
Entities:
Keywords:
Cannabis; Cognition; Early psychosis; Glutamate; Magnetic resonance spectroscopy
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