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

Claudio D'Addario, Vincenzo Micale, Martina Di Bartolomeo, Tibor Stark, Mariangela Pucci, Alexandra Sulcova, Mariacarlotta Palazzo, Zuzana Babinska, Laura Cremaschi, Filippo Drago, A Carlo Altamura, Mauro Maccarrone, Bernardo Dell'Osso

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Abstract

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.

Original languageEnglish
Pages (from-to)132-140
Number of pages9
JournalSchizophrenia Research
Volume188
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Journal Article

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    D'Addario, C., Micale, V., Di Bartolomeo, M., Stark, T., Pucci, M., Sulcova, A., Palazzo, M., Babinska, Z., Cremaschi, L., Drago, F., Carlo Altamura, A., Maccarrone, M., & Dell'Osso, B. (2017). A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia. Schizophrenia Research, 188, 132-140. https://doi.org/10.1016/j.schres.2017.01.022