Metabotropic glutamate receptor 5 binding in patients with obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.
Psychiatric University Hospital, University of Bern,BernSwitzerland.
Funda
F
Akkus
Psychiatric University Hospital, University of Bern,BernSwitzerland.
Sylvia
S
Terbeck
Department of Chemistry and Applied Biosciences of ETH,Centre for Radiopharmaceutical Science of ETH,PSI and USZ, Zurich,Switzerland.
Simon M
SM
Ametamey
Department of Psychiatry and Psychotherapy,University Hospital,Zurich,Switzerland.
Michael
M
Rufer
PET Centre, Division of Nuclear Medicine,University Hospital,Zurich,Switzerland.
Valerie
V
Treyer
PET Centre, Division of Nuclear Medicine,University Hospital,Zurich,Switzerland.
Cyrill
C
Burger
Department of Chemistry and Applied Biosciences of ETH,Centre for Radiopharmaceutical Science of ETH,PSI and USZ, Zurich,Switzerland.
Anass
A
Johayem
Novartis Institutes for BioMedical Research,Novartis Pharma AG, Basel,Switzerland.
Baltazar Gomez
BG
Mancilla
Novartis Institutes for BioMedical Research,Novartis Pharma AG, Basel,Switzerland.
Judit
J
Sovago
PET Centre, Division of Nuclear Medicine,University Hospital,Zurich,Switzerland.
Alfred
A
Buck
Psychiatric University Hospital, University of Bern,BernSwitzerland.
Gregor
G
Hasler
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D009771:Obsessive-Compulsive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D010091:Oximes; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*
C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; C578935:GRM5 protein, human; D010091:Oximes; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5