Cannabinoid receptor subtype 1 (CB1) distribution and neuropsychiatric ratings

Objectives In our previous study (Wong et al, 2010), we compared healthy controls and patients with schizophrenia using the Cannabinoid receptor type 1 (CB1) PET tracer, [¹¹C]OMAR (JHU 75528), and showed evidence of a relationship between CB1 volume of distribution (V_T) and subscores of the Brief Psychiatric Rating Scale (BPRS). In this study, we use Statistical Parametric Mapping (SPM) to examine CB1 V_T in healthy controls, patients, and the relationship with psychiatric symptoms.

Methods We studied ten healthy controls (1 female, 9 male; age 33±11years) and nine patients with schizophrenia (2 female, 7 male; age 42±9years) using [¹¹C]OMAR brain PET. Subjects with recent drug abuse history were excluded. Parametric maps were generated using plasma reference graphical analysis(PRGA), the most robust kinetic modeling method for CB1 distribution, as previously described. Maps were then smoothed with a 12 mm filter, before SPM analysis.

Results We first examined group differences between controls and patients, but did not find any clusters (threshold volume = 20 voxels) with a significant difference. We then examined the relationship of CB1 V_T, co-varying for age, with psychiatric test variables, specifically the ratio of BPRS psychosis to BPRS withdrawal. Using the PRGA maps, we found 2 significant clusters of greater than 30 voxels where CB1 correlated positively with psychosis/withdrawal (P/W) ratio: 1) Talairach coordinates [-42, -4, 36 mm], FDR-corrected p = 0.015, peak t = 12.78 and 2) [-4, -38, 28 mm], FDR-corrected p = 0.015, peak t = 10.8.

Conclusions The clusters where we see a significant positive correlation of CB1 V_T with P/W ratio correspond to the middle/posterior portions of the cingulate (extending into the pre-motor cortical area), comparable to the trend-level correlations reported previously (Wong, et al, 2010). Therefore voxel-based analysis is consistent with previous published region-based analyses.

Research Support Sanofi-Aventis, NIH DA000412, MH079017, S10RR023623-01 and S10RR01721