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Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex

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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.

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Acknowledgements

We would like to thank all patients and control subjects for their enduring participation. We are grateful for support from the Loterie Romande, Avina Foundation, Damm-Etienne Foundation, Pro Scientia et Arte Foundation, Alamaya Foundation and Sapienza University of Rome—“Avvio alla Ricerca.”

Funding

This work was supported by the Swiss National Science Foundation (320030_122419 to P.C. and K.Q.D), National Center of Competence in Research (NCCR) “SYNAPSY (P.K and L.A - The Synaptic Bases of Mental Diseases” financed by the Swiss National Science Foundation (n° 51AU40_125759). P.S.B. was supported by the Leenaards and Jeantet foundation. Magnetic resonance spectroscopy war performed in the Centre d’Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL.

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Author notes

  1. Kim Q. Do and Philippe Conus are equal contribution.

Authors and Affiliations

  1. TIPP (Treatment and Early Intervention in Psychosis Program); Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland

    Silvia Rigucci, Paul Klauser, Philipp S. Baumann, Luis Alameda, Carina Ferrari & Philippe Conus

  2. Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland

    Silvia Rigucci, Paul Klauser, Philipp S. Baumann, Luis Alameda, Martine Cleusix, Raoul Jenni & Kim Q. Do

  3. Department of Neurosciences, Sensory Organs and Mental Health, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy

    Silvia Rigucci & Maurizio Pompili

  4. Animal imaging and technology core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Lijing Xin

  5. Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Rolf Gruetter

  6. Departments of Radiology, University of Lausanne, Lausanne, Switzerland

    Rolf Gruetter

  7. Department of Radiology, University of Geneva, Geneva, Switzerland

    Rolf Gruetter

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  1. Silvia Rigucci
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  2. Lijing Xin
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Corresponding author

Correspondence to Kim Q. Do.

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Silvia Rigucci and Lijing Xin are co first authors.

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Rigucci, S., Xin, L., Klauser, P. et al. Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex. Psychopharmacology 235, 13–22 (2018). https://doi.org/10.1007/s00213-017-4745-z

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  • DOI: https://doi.org/10.1007/s00213-017-4745-z

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