Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex

A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB 1 receptor (CB 1 R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB 1 R ligand [ 3 H] CP 55 940 and CB 1 R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB 1 R expression. There was a main effect of diagnosis on [ 3 H] CP 55 940 binding quantified across all layers of the DLPFC (F(2,71)=3.740, p =0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB 1 R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67)=6.048, p =0.004) with paranoid SCZ patients differing significantly from the control ( p =0.004) and from the non-paranoid group ( p =0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB 1 R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.