Abdallah Chadi G, Hannestad Jonas, Mason Graeme F, Holmes Sophie E, DellaGioia Nicole, Sanacora Gerard, Jiang Lihong, Matuskey David, Satodiya Ritvij, Gasparini Fabrizio, Lin Xin, Javitch Jonathan, Planeta Beata, Nabulsi Nabeel, Carson Richard E, Esterlis Irina
Yale University School of Medicine, Department of Psychiatry, New Haven, CT.
Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Jul;2(5):449-456. doi: 10.1016/j.bpsc.2017.03.019. Epub 2017 Apr 6.
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.
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).
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.
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.
临床前和尸检研究表明，代谢型谷氨酸受体5（mGluR5）与重度抑郁症（MDD）的病理生理学有关。本研究的目的是通过[F]FPEB和正电子发射断层扫描（PET），确定mGluR5在一大群MDD患者与健康对照（HC）中的作用。此外，我们试图确定谷氨酸在MDD中对mGluR5可用性的作用。
65名参与者（30名MDD患者和35名HC）完成了[F]FPEB PET，以估计主要结局指标——mGluR5分布容积（），以及次要结局指标——mGluR5分布容积比率（）。39名参与者的亚组（16名MDD患者和23名HC）完成了质子磁共振波谱（H MRS），以估计前扣带回（ACC）中谷氨酸、谷氨酰胺和Glx（谷氨酸+谷氨酰胺）相对于肌酸（Cr）的水平。
在mGluR5方面未观察到显著的组间差异。与HC相比，MDD患者的ACC谷氨酸、谷氨酰胺和Glx水平更高。重要的是，ACC的mGluR5与谷氨酸/Cr和Glx/Cr水平呈负相关。
在这项新颖的研究中，我们显示了mGluR5可用性与谷氨酸水平之间的负相关关系。这些数据突出了进一步研究谷氨酸能系统在抑郁症中作用的必要性。
