Cannabinoid Receptor 1 (CNR1) Gene Polymorphisms in Schizophrenia Patients: Rs6454674 Polymorphism is Associated with Disease Severity

Abstract

Objective: The endocannabinoid system contributes to the regulation of emotions, stress, memory, and cognition. It has been reported that endocannabinoids cause GABAergic inhibition and dopaminergic increase in the mesolimbic and nigrostriatal systems, thus playing a part in the neurobiology of schizophrenia. In this study, we investigate cannabinoid receptor 1 (CNR1) gene polymorphisms in schizophrenia patients. Methods: CNR1 gene polymorphisms were studied in 66 schizophrenia patients and 65 healthy controls. To obtain genomic DNA, proteinase K digestion and the salt-chloroform method were used. Clinical Global Impression severity scale (CGI-S) and Positive and Negative Syndrome Scale (PANSS) were administered to evaluate the severity of schizophrenia symptoms. CNR1 gene polymorphism was determined by using polymerase chain reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and Single Strand Conformation Polymorphism (SSCP) methods for the Rs6454674, Rs806368, and Rs1049353 sites. Results: There was no difference in CNR1 gene polymorphisms between schizophrenia patients and control groups (Rs6454674 T/G; p=0.973, Rs806368 T/C; p=0.349, Rs1049353 A/G; p=1.00). However, CGI-S, PANSS total, PANSS positive, PANSS negative and PANSS general psychopathology scores were significantly lower in schizophrenia patients with RS6454674 polymorphism than in those not showing polymorphism. Conclusion: Our results suggest that CNR1 gene polymorphisms may be associated with clinical symptoms and disease severity in schizophrenia patients.