TY - JOUR
T1 - A preliminary study of endocannabinoid system regulation in psychosis
T2 - Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia
AU - D'Addario, Claudio
AU - Micale, Vincenzo
AU - Di Bartolomeo, Martina
AU - Stark, Tibor
AU - Pucci, Mariangela
AU - Sulcova, Alexandra
AU - Palazzo, Mariacarlotta
AU - Babinska, Zuzana
AU - Cremaschi, Laura
AU - Drago, Filippo
AU - Carlo Altamura, A.
AU - Maccarrone, Mauro
AU - Dell'Osso, Bernardo
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - Cannabinoid receptor type-1
KW - DNA methylation
KW - Endocannabinoid system (ECS)
KW - Methylazoxymethanol (MAM) rat model
KW - Schizophrenia
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U2 - 10.1016/j.schres.2017.01.022
DO - 10.1016/j.schres.2017.01.022
M3 - Article
AN - SCOPUS:85009775090
VL - 188
SP - 132
EP - 140
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
ER -