|We recently demonstrated that measures of CB1R mRNA and protein were significantly reduced in DLPFC area 9 in schizophrenia subjects relative to matched normal comparison subjects. However, other studies have reported unaltered or higher measures of CB1R levels in schizophrenia. To determine whether these discrepancies reflect differences across brain regions or across subject groups (e.g., presence of depression, cannabis exposure, etc), we used
immunocytochemical techniques to determine whether lower levels of CB1R immunoreactivity are 1) present in another DLPFC region, area 46, in the same subjects with schizophrenia, 2) present in area 46 in a new cohort of schizophrenia subjects, 3) present in major depressive disorder (MDD) subjects, or 4) attributable to factors other than a diagnosis of schizophrenia, including prior cannabis use. CB1R immunoreactivity levels in area 46 were significantly 19% lower in schizophrenia subjects relative to matched normal comparison subjects, a deficit similar to that observed in area 9 in the same subjects. In a new cohort of subjects, CB1R
immunoreactivity levels were significantly 20% and 23% lower in schizophrenia subjects relative to matched comparison and MDD subjects, respectively. As shown in the figure, intense CB1R immunoreactivity was localized to axons and varicosities in a distinctive laminar pattern, but the density of labeled profiles was lower in the subject with schizophrenia (B) than in the matched control subject (A) or subject with MDD (C). Lower levels of CB1R immunoreactivity in schizophrenia subjects were not explained by other factors such as cannabis use, suicide, or pharmacological treatment. In addition, CB1R immunoreactivity levels were not altered in monkeys chronically exposed to haloperidol. Thus, lower levels of CB1R immunoreactivity may be common in schizophrenia, conserved across DLPFC regions, not present in MDD, and not attributable to other factors, and thus a reflection of the underlying disease process.