title: Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia.
abstract: Increasing animal genetic, post-mortem and pharmacological evidence supports a role for the cerebral type 1 cannabinoid (CB1) receptor in the pathogenesis of schizophrenia (SCZ) and/or neural circuit dysfunctions responsible for its symptomatology. Moreover, since important interspecies differences are present in CB1 receptor expression, in vivo human data are of direct interest. We investigated an in vivo CB1 receptor expression in SCZ patients compared to healthy controls (CON), and in relation with psychopathological symptom severity using positron emission tomography (PET) and the selective high-affinity radioligand [(18)F]MK-9470. A total of sixty-seven patients with SCZ, with (SCZ-T, n=51) and without (SCZ-F, n=16) antipsychotic treatment, and 12 age and gender-matched CON were investigated with [(18)F]MK-9470 PET. Parametric modified standardized uptake value (mSUV) images, reflecting CB1 receptor binding, were compared and related to psychopathological symptoms. Compared to CON, there was a significant increase of CB1 receptor binding in SCZ patients in the nucleus accumbens, insula, cingulate cortex, inferior frontal cortex, parietal and mediotemporal lobe. Furthermore, in the SCZ-F group only, CB1 receptor binding was negatively correlated to negative symptoms and to depression scores, especially in the nucleus accumbens. Present findings strongly support that CB1 receptor binding is altered in the mesocorticolimbic circuitry of both SCZ-T and SCZ-F patients, especially in the nucleus accumbens. In SCZ-F patients, it is associated with negative symptoms and depression scores.
authors.affiliation: Division of Nuclear Medicine, University Hospitals Leuven & Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. jenny.ceccarini@uzleuven.be
authors.forename: Jenny
authors.initials: J
authors.lastname: Ceccarini
authors.forename: Marc
authors.initials: M
authors.lastname: De Hert
authors.forename: Ruud
authors.initials: R
authors.lastname: Van Winkel
authors.forename: Joseph
authors.initials: J
authors.lastname: Peuskens
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Laura
authors.initials: L
authors.lastname: Kranaster
authors.forename: Frank
authors.initials: F
authors.lastname: Enning
authors.forename: Dagmar
authors.initials: D
authors.lastname: Koethe
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D013223:Statistics as Topic; D014018:Tissue Distribution
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1