A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia

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Authors

ADDARIO D. MICALE Vincenzo DI BARTOLOMEO M. ŠTARK Tibor PUCCI M. ŠULCOVÁ Alexandra PALAZZO M. BABINSKÁ Zuzana CREMASCHI L. DRAGO F. ALTAMURA C.A. MACCARRONE M. DELL'OSSO B.

Year of publication 2017
Type Article in Periodical
Magazine / Source Schizophrenia Research
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1016/j.schres.2017.01.022
Field Psychiatry, sexuology
Keywords Endocannabinoid system (ECS); Cannabinoid receptor type-1; DNA methylation; Schizophrenia; Methylazoxymethanol (MAM) rat model
Description Compelling evidence supports the involvement of the endocannabinoid system(ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1, the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients (N = 25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure (N = 7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia. (C) 2017 Elsevier B.V. All rights reserved.
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