Enhanced mGluR5 availability marks the antidepressant efficacy in major depressive disorder: an [18F]FPEB PET study

Abstract

The limited efficacy of antidepressants for major depressive disorder (MDD) underscores the urgent need to explore mechanisms behind treatment heterogeneity and identify new antidepressant targets. This study explores the role of metabotropic glutamate receptor 5 (mGluR5) in MDD, examining mGluR5 availability changes pre- and post-treatment, and their link to clinical outcomes. We studied 25 patients with MDD and 21 healthy controls, with 13 undergoing eight-week vortioxetine treatment (10 mg per day). mGluR5 availability was measured at baseline and follow-up using [18F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile positron emission tomography ([18F]FPEB PET) scans, and patients were categorized on the basis of their response. Results showed lower mGluR5 availability in patients with MDD versus the control group at baseline. Post-treatment, the group with MDD exhibited significant increases in mGluR5 availability in the dorsolateral prefrontal cortex and ventromedial prefrontal cortex (N = 13, Cohen’s d = 0.83 and 1.01). The percentage increase in mGluR5 availability correlated with the percentage reduction in scores on the Hamilton rating scale for depression. These findings underscore mGluR5’s key role in MDD pathophysiology and treatment. This study found that mGluR5 availability is lower in patients with MDD and increases after treatment, correlating with symptom improvement, highlighting the role of mGluR5 role in MDD pathophysiology and treatment response.