Background: Preclinical and postmortem studies have implicated the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of major depressive disorder (MDD). The goal of the present study was to determine the role of mGluR5 in a large group of individuals with MDD compared to healthy controls (HC) with [F]FPEB and positron emission tomography (PET). Furthermore, we sought to determine the role glutamate plays on mGluR5 availability in MDD.
Methods: Sixty-five participants (30 MDD and 35 HC) completed [F]FPEB PET to estimate the primary outcome measure - mGluR5 volume of distribution (), and the secondary outcome measure - mGluR5 distribution volume ratio (). A subgroup of 39 participants (16 MDD and 23 HC) completed proton magnetic resonance spectroscopy (H MRS) to estimate anterior cingulate (ACC) glutamate, glutamine, and Glx (glutamate + glutamine) levels relative to creatine (Cr).
Results: No significant between-group differences were observed in mGluR5 . Compared to HC, individuals with MDD had higher ACC glutamate, glutamine, and Glx levels. Importantly, the ACC mGluR5 negatively correlated with glutamate/Cr and Glx/Cr levels.
Conclusions: In this novel examination, we show an inverse relationship between mGluR5 availability and glutamate levels. These data highlight the need to further investigate the role of glutamatergic system in depression.
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| http://dx.doi.org/10.1016/j.bpsc.2017.03.019 | DOI Listing |
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