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Objective: Endocannabinoid system is involved in regulation of emotion, stress, memory, and cognition. Dysfunctions of this system may lead to various psychiatric disorders such as schizophrenia, bipolar disorder, anxiety disorders, and depression. Mutations on the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid 1 (CB1) receptors are associated with several psychiatric disorders. CB1 are highly expressed in olfactory receptor system, hippocampal formation, the basal ganglion, cerebellum and neocortex in the brain. The main cannabinoid receptor is CB1 and by the activation of them leads an inhibition on neuronal depolarization; diminish in the production of action potential, and releasing of excitatory and inhibitory neurotransmitters. Thus causes a decrease in impulse propagation. Receptor agonists for CB1 act like antidepressants by the activation of 5-HT neurotransmission. On the other hand, antagonism of CB1 receptors may lead depression like clinical pictures in some patients. Cannabinoid usage may lead to the early onset of BD, and sometimes induce BD in susceptible individuals. Taken all together, we aimed to make research on the possible association between the CNR1 gene polymorphisms and BD.
Methods: A total of 96 patients and 58 healthy controls were registered in the current case-control study. Blood samples of study participants were collected into sterile tubes and processed to obtain genomic DNA. To obtain genomic DNA, proteinase K digestion and salt-chloroform method was utilized. Polymerase Chain Reaction and Amplification of DNA samples were achieved in AB Thermal Cycler (ABI Inc. CA, USA). Amplified PCR products were verified by running through 2% agarose gel and visualized using ethidium bromide stain. Restriction Fragment Length Polymorphism analysis were analyzed digesting the PCR products with HpyCH4III and BseGI enzymes for the rs6454674 and rs806368 restriction sites, respectively (Table 1). Single-Strand Conformation Polymorphism (SSCP) analyses were performed.
Results: The comparison of the patients and control groups according to the three polymorphisms has not shown any significant difference (Rs6454674 T/G; p>0.05, Rs806368 T/C; p>0.05, Rs1049353 A/G; p>0.05). When patients were compared with the presence of past suicide attempts, the scores that shows the severity of the illness, total number of episodes, duration of the illness, and mutated allele for each polymorphisms we did not find any significant difference.
Conclusions: To the best of our knowledge, it is the first study that investigated the possible association of three CNR1 gene polymorphisms in BD alone. In recent years, BD and major depressive patients were enrolled in a study that found the parallel results with the present study and no relationship between BD and CNR1 rs1049353 A/G polymorphism and alleles. Although results of both studies reveal that there was not any relationship between CNR1 and BD, there is a need for further and large sample sized studies on this issue.