title: Metabotropic glutamate receptor 5 neuroimaging in schizophrenia.
abstract: The metabotropic glutamate receptor 5 (mGluR5) is a promising drug target for the treatment of schizophrenia. In this study, we compared mGluR5 distribution volume ration (DVR) in subjects with schizophrenia and healthy controls. Given our previous findings, we matched samples for gender, age, and smoking status. Binding to mGluR5 was determined using positron emission tomography and [11C]ABP688, which binds to an allosteric site with high selectivity. DVR in the 15 individuals with schizophrenia did not differ from that of the 15 controls. In both groups, smoking was associated with marked global reductions in mGluR5 availability (on average 23.8%). In nonsmoking subjects with schizophrenia, there was a positive correlation between mGluR5 DVR in the medial orbitofrontal cortex and the use of antipsychotic drugs (r=0.9, p=0.019). Because antipsychotic drugs such as clozapine appeared to have indirect effects on mGluR5 signaling, our findings may be clinically relevant. They also provide promising leads for elucidating the high comorbidity between schizophrenia and tobacco addiction. Low mGluR5 DVR in smokers my represent a risk factor for schizophrenia. Alternatively, smoking may counteract the potential upregulation of mGluR5 by antipsychotic drugs.
authors.affiliation: Psychiatric University Hospital, University of Bern, 3000 Bern 60, Switzerland.
authors.forename: Funda
authors.initials: F
authors.lastname: Akkus
authors.affiliation: PET Center, Division of Nuclear Medicine, University Hospital, 8091 Zurich, Switzerland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Treyer
authors.affiliation: Center for Radiopharmaceutical Science of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, 8093 Zurich, Switzerland.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.affiliation: PET Center, Division of Nuclear Medicine, University Hospital, 8091 Zurich, Switzerland.
authors.forename: Anass
authors.initials: A
authors.lastname: Johayem
authors.affiliation: PET Center, Division of Nuclear Medicine, University Hospital, 8091 Zurich, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Psychiatric University Hospital, University of Bern, 3000 Bern 60, Switzerland. Electronic address: gregor.hasler@puk.unibe.ch.
authors.forename: Gregor
authors.initials: G
authors.lastname: Hasler
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010091:Oximes / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000493:pharmacokinetics; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D012907:Smoking / Q000523:psychology; D013223:Statistics as Topic
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5
keywords: Glutamate; Nicotine; Positron emission tomography; Schizophrenia; mGluR5