Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study

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 bindin...

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Veröffentlicht in:The American journal of psychiatry Jg. 168; H. 7; S. 727
Hauptverfasser: Deschwanden, Alexandra, Karolewicz, Beata, Feyissa, Anteneh M, Treyer, Valerie, Ametamey, Simon M, Johayem, Anass, Burger, Cyrill, Auberson, Yves P, Sovago, Judit, Stockmeier, Craig A, Buck, Alfred, Hasler, Gregor
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.07.2011
Schlagworte:
Adult
Brain - diagnostic imaging
Brain - metabolism
Carbon Radioisotopes
Depressive Disorder, Major - diagnosis
Depressive Disorder, Major - diagnostic imaging
Depressive Disorder, Major - metabolism
Female
Humans
Male
Middle Aged
Oximes
Positron-Emission Tomography - statistics & numerical data
Prefrontal Cortex - diagnostic imaging
Prefrontal Cortex - metabolism
Pyridines
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Receptors, Metabotropic Glutamate - metabolism
Tissue Distribution
ISSN:1535-7228
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Zusammenfassung: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. 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. 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. 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.
ISSN:1535-7228
DOI:10.1176/appi.ajp.2011.09111607