title: A voxel-by-voxel analysis of [18F]setoperone PET data shows no substantial serotonin 5-HT(2A) receptor changes in schizophrenia.
abstract: Several postmortem studies have reported regionally localized decreases in serotonin(2A) receptors (5-HT(2A)R) in schizophrenia. This was not confirmed by two recent [18F]setoperone positron emission tomography (PET) studies. In these two studies relatively large regions of interest (ROIs) were used; hence, 5-HT(2A)R 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-HT(2A)R binding potential (BP) and five PANSS-derived factors: negative, positive, activation, dysphoric and autistic preoccupation. Thirteen schizophrenic patients (10 antipsychotic-naïve, 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-HT(2A)R BP was determined for each voxel using the pseudoequilibrium ratio method on PET data obtained between 65 and 90 min after [18F]setoperone bolus injection. The resulting parametric 5-HT(2A)R 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-HT(2A)R 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-HT(2A)R 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-HT(2A)R BP differences between schizophrenic patients and control subjects.
authors.affiliation: PET Centre and Schizophrenia and Continuing Care Division, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, ON, M5T 1R8, Toronto, Canada. paul_verhoeff@camh.net
authors.forename: N P
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: J H
authors.initials: JH
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Kecojevic
authors.forename: D
authors.initials: D
authors.lastname: Hussey
authors.forename: R
authors.initials: R
authors.lastname: Lewis
authors.forename: J
authors.initials: J
authors.lastname: Tauscher
authors.forename: R B
authors.initials: RB
authors.lastname: Zipursky
authors.forename: S
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D003287:Contrast Media; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011744:Pyrimidinones; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012702:Serotonin Antagonists; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D003287:Contrast Media; D005462:Fluorine Radioisotopes; D011744:Pyrimidinones; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C045359:setoperone