title: Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study.
abstract: OBJECTIVE
  Clinical and preclinical evidence suggests a hyperactive glutamatergic system in clinical depression. Recently, the metabotropic glutamate receptor 5 (mGluR5) has been proposed as an attractive target for novel therapeutic approaches to depression. The goal of this study was to compare mGluR5 binding (in a positron emission tomography [PET] study) and mGluR5 protein expression (in a postmortem study) between individuals with major depressive disorder and psychiatrically healthy comparison subjects.
  
  
  METHODS
  Images of mGluR5 receptor binding were acquired using PET with [(11)C]ABP688, which binds to an allosteric site with high specificity, in 11 unmedicated individuals with major depression and 11 matched healthy comparison subjects. The amount of mGluR5 protein was investigated using Western blot in postmortem brain samples of 15 depressed individuals and 15 matched comparison subjects.
  
  
  RESULTS
  The PET study revealed lower levels of regional mGluR5 binding in the prefrontal cortex, the cingulate cortex, the insula, the thalamus, and the hippocampus in the depression group relative to the comparison group. Severity of depression was negatively correlated with mGluR5 binding in the hippocampus. The postmortem study showed lower levels of mGluR5 protein expression in the prefrontal cortex (Brodmann's area 10) in the depression group relative to the comparison group, while prefrontal mGluR1 protein expression did not differ between groups.
  
  
  CONCLUSIONS
  The lower levels of mGluR5 binding observed in the depression group are consonant with the lower levels of protein expression in brain tissue in the postmortem depression group. Thus, both studies suggest that basal or compensatory changes in excitatory neurotransmission play roles in the pathophysiology of major depression.
authors.affiliation: PET Center, Division of Nuclear Medicine, University Hospital, Zurich.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Deschwanden
authors.forename: Beata
authors.initials: B
authors.lastname: Karolewicz
authors.forename: Anteneh M
authors.initials: AM
authors.lastname: Feyissa
authors.forename: Valerie
authors.initials: V
authors.lastname: Treyer
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Anass
authors.initials: A
authors.lastname: Johayem
authors.forename: Cyrill
authors.initials: C
authors.lastname: Burger
authors.forename: Yves P
authors.initials: YP
authors.lastname: Auberson
authors.forename: Judit
authors.initials: J
authors.lastname: Sovago
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.forename: Gregor
authors.initials: G
authors.lastname: Hasler
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010091:Oximes; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; C578935:GRM5 protein, human; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate