A voxel-by-voxel analysis of [18F]setoperone PET data shows no substantial serotonin 5-HT2A receptor changes in schizophrenia

Several postmortem studies have reported regionally localized decreases in serotonin,, receptors (5-HT2AR) in schizophrenia. This was not confirmed by two recent [F-18]setoperone positron emission tomography (PET) studies. In these two studies relatively large regions of interest (ROIs) were used; hence, 5-HT2AR changes may have been missed in some brain areas. Therefore, data from one study were analyzed on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM). We also used this method to examine the relationship between 5-HT2AR binding potential (BP) and five PANSS-derived factors: negative, positive, activation, dysphoric and autistic preoccupation. Thirteen schizophrenic patients (10 antipsychotic-naive, 3 antipsychotic-free; 11 M, 2 F; age 31 +/- 7 years) and 35 age-matched control subjects (15 M, 20 F; age 30 +/- 7 years) were scanned. The 5-HT2AR BP was determined for each voxel using the pseudoequilibrium ratio method on PET data obtained between 65 and 90 min after [F-18]setoperone bolus injection. The resulting parametric 5-HT2AR BP images were spatially normalized using a ligand specific template. Analyses of covariance were done using SPM99 with age as covariate. In tests for the effect of schizophrenia and for partial correlations between 5-HT2AR BP and the five factors, corrected P values < 0.05 at cluster or voxel level were considered significant. No significant differences were detected between patients and control subjects, and no significant correlations were observed between 5-HT2AR BP and any of the five factors. Thus, in agreement with the previous ROI studies, voxel-by-voxel analysis confirmed the lack of substantial 5-HT2AR BP differences between schizophrenic patients and control subjects. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.