Reduced Brain Cannabinoid Receptor Availability in Schizophrenia

Abstract

Background: Several lines of evidence suggest the presence of abnormalities in the endocannabinoid (eCB) system in schizophrenia (SCZ). However, there are limited in vivo measures of the eCB system in SCZ.

Methods: Twenty five male SCZ subjects (SCZs) (18 antipsychotic treated and 7 antipsychotic free) were compared with 18 age-matched male healthy control subjects (HCs). Subjects underwent one positron emission tomography scan each with the cannabinoid receptor-1 (CB1R) selective radiotracer [(11)C]OMAR on the high resolution research tomography scanner. Regional volume of distribution (VT) values were determined using kinetic modeling of positron emission tomography data as a measure of CB1R availability. Group differences in mean composite [(11)C]OMAR VT values were compared between SCZs and HCs. Exploratory comparisons of CB1R availability within 15 brain regions were also conducted. All analyses were covaried for age and body mass index.

Results: SCZs showed significantly (p = .02) lower composite [(11)C]OMAR VT relative to HCs (~12% difference, effect size d = .73). [(11)C]OMAR VT was significantly (all ps < .05) lower in SCZs in the amygdala, caudate, posterior cingulate cortex, hippocampus, hypothalamus, and insula. Composite [11]OMAR VT was HCs > antipsychotic treated SZCs > antipsychotic free SZCs. Furthermore, composite [(11)C]OMAR VT was greater in HCs than SCZ smokers (n = 11) and SCZ nonsmokers (n = 14).

Conclusions: CB1R availability is lower in male SCZ subjects compared with HCs. Furthermore, antipsychotics and tobacco use may increase CB1R availability in this population. The findings of the study provide further evidence supporting the hypothesis that alterations in the eCB system might contribute to the pathophysiology of SCZ.

Trial registration: ClinicalTrials.gov NCT01730781.

Keywords: Antipsychotics; CB(1)R; Cannabinoid; OMAR; Schizophrenia; Smoking.

Conflict of interest statement

Disclosure: All other authors report no biomedical financial interests or potential conflicts of interest.

Published by Elsevier Inc.

Figures

Figure 1. Grand Averaged CB1R availability in Schizophrenia Patients vs. Healthy Controls

Top row: HC averaged (n=21) of the distribution volume (VT; Innis et al., 2007) images computed using the multilinear analysis (MA1; Ichise et al., 2002) Middle row: SCZ averaged (n=25) of the distribution volume (VT; Innis et al., 2007) images computed using the multilinear analysis (MA1; Ichise et al., 2002) Bottom row: Aligned T1 MR image for anatomical reference

Figure 2. CB1R availability in Schizophrenia Patients vs. Healthy Controls

The figure shows the mean and standard error bars of [11C]OMAR Volume of Distribution (VT). Significant differences (p<0.05) between groups are indicated with *. Trend differences (p<0.06–0.1) between groups are indicated with #.

Figure 3. Effects of Antipsychotic Treatment on CB1R availability

The figure shows the mean and standard error bars of [11C]OMAR Volume of Distribution (VT). See text for statistically significant differences between 3 groups. *p = 0.025. #p = 0.07.

Figure 4. Effects of Tobacco Smoking on CB1R availability

The figure shows the mean and standard error bars of [11C]OMAR Volume of Distribution (VT). See text for statistically significant differences between 3 groups. *p = 0.006. #p = 0.096.