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.
A preliminary study of endocannabinoid system regulation in psychosis : distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia / C. D'Addario, V. Micale, M. Di Bartolomeo, T. Stark, M. Pucci, A. Sulcova, M. Palazzo, Z. Babinska, L. Cremaschi, F. Drago, A.C. Altamura, M. Maccarrone, B. Dell'Osso. - In: SCHIZOPHRENIA RESEARCH. - ISSN 0920-9964. - 188(2017 Jan 17), pp. 132-140.
|Titolo:||A preliminary study of endocannabinoid system regulation in psychosis : distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia|
DELL'OSSO, BERNARDO MARIA (Ultimo)
|Parole Chiave:||Cannabinoid receptor type-1; DNA methylation; Endocannabinoid system (ECS); Methylazoxymethanol (MAM) rat model; Schizophrenia; Psychiatry and Mental Health; Biological Psychiatry|
|Settore Scientifico Disciplinare:||Settore MED/25 - Psichiatria|
|Data di pubblicazione:||ott-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.schres.2017.01.022|
|Appare nelle tipologie:||01 - Articolo su periodico|