CNR2 GENE AND CANNABIS USE INTERPLAY MODULATES MANIPULATIVE ABILITIES IN FIRST-EPISODE OF PSYCHOSIS

1.

Objectives: While endocannabinoid system seems to be involved in processes underlying psychosis, research about Cannabinoid Receptor 2 gene (CNR2) is scarce and inconclusive. Some few reports indicate that CNR2 plays a role in psychiatric conditions, including depression or drug addiction (Onaivi et al., 2009). We aimed to evaluate the role of CNR2 and its interplay with cannabis on cognition and clinical symptoms in patients with a first-episode of psychosis (FEP). 2.

Materials and Methods: the sample comprised 50 Caucasian individuals with a FEP (mean age(sd)=26.14(6.55) years, 76% males, 58% cannabis users). There were no differences in age, sex, premorbid IQ and antipsychotic dose between cannabis users (CU) and non-users (CNU). Neuropsychological (premorbid IQ - TAP-E, current IQ - WAIS, memory - WMS, executive function - BADS) and clinical (psychotic symptoms - PANSS, general functioning - GAF) scales were administered. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in CNR2 gene (rs2501431) (qPCR, TaqMan). 3. Results and

Conclusions: genotypic frequencies did not differ between cannabis users and non-users. CNR2 was not associated with PANSS scores.; however, it showed a differential effect on the performance IQ (measured by the matrix reasoning test - WAIS), conditional to the cannabis use (beta=0.73, p=0.02),. In particular, cannabis non-users with the AA genotype (23.53%) showed higher scores (mean(sd)=10.25 (1.87)) than those with at least one copy of the G allele (76.47%, mean(sd)=6.05(0.99); while cannabis users showed scores in the opposite direction (AA (42.31%): 8.21(1.09) and GG/GA (57.69%): 10.28(0.92)). Our results align with previous studies reporting the association of the CNR2 gene with psychiatric diseases (Ishiguro et al. 2007; Onaivi et al., 2008) adding evidence on the interplay of this gene with cannabis use on cognitive outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.