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

Alexandra Deschwanden, Beata Karolewicz, Anteneh Feyissa, Valerie Treyer, Simon M. Ametamey, Anass Johayem, Cyrill Burger, Yves P. Auberson, Judit Sovago, Craig A. Stockmeier, Alfred Buck, Gregor Hasler

Research output: Contribution to journalArticle

141 Citations (Scopus)

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. Method: Images of mGluR5 receptor binding were acquired using PET with [ 11C]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.

Original languageEnglish (US)
Pages (from-to)727-734
Number of pages8
JournalAmerican Journal of Psychiatry
Volume168
Issue number7
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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Metabotropic Glutamate 5 Receptor
Positron-Emission Tomography
Depression
Proteins
Prefrontal Cortex
Hippocampus
Healthy Volunteers
Allosteric Site
3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
Gyrus Cinguli
Major Depressive Disorder
Brain
Thalamus
Synaptic Transmission
Western Blotting

ASJC Scopus subject areas

  • Psychiatry and Mental health

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Reduced metabotropic glutamate receptor 5 density in major depression determined by [11C]ABP688 PET and postmortem study. / Deschwanden, Alexandra; Karolewicz, Beata; Feyissa, Anteneh; Treyer, Valerie; Ametamey, Simon M.; Johayem, Anass; Burger, Cyrill; Auberson, Yves P.; Sovago, Judit; Stockmeier, Craig A.; Buck, Alfred; Hasler, Gregor.

In: American Journal of Psychiatry, Vol. 168, No. 7, 01.07.2011, p. 727-734.

Research output: Contribution to journalArticle

Deschwanden, A, Karolewicz, B, Feyissa, A, Treyer, V, Ametamey, SM, Johayem, A, Burger, C, Auberson, YP, Sovago, J, Stockmeier, CA, Buck, A & Hasler, G 2011, 'Reduced metabotropic glutamate receptor 5 density in major depression determined by [11C]ABP688 PET and postmortem study', American Journal of Psychiatry, vol. 168, no. 7, pp. 727-734. https://doi.org/10.1176/appi.ajp.2011.09111607
Deschwanden, Alexandra ; Karolewicz, Beata ; Feyissa, Anteneh ; Treyer, Valerie ; Ametamey, Simon M. ; Johayem, Anass ; Burger, Cyrill ; Auberson, Yves P. ; Sovago, Judit ; Stockmeier, Craig A. ; Buck, Alfred ; Hasler, Gregor. / Reduced metabotropic glutamate receptor 5 density in major depression determined by [11C]ABP688 PET and postmortem study. In: American Journal of Psychiatry. 2011 ; Vol. 168, No. 7. pp. 727-734.
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