Enhanced mGluR5 Availability Marks the Antidepressant Efficacy in Major Depressive Disorder

The limited efficacy of antidepressants for Major Depressive Disorder (MDD) underscores the need for novel 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 MDD patients and 21 healthy controls, with 13 undergoing eight-week vortioxetine treatment. mGluR5 availability was measured at baseline and follow-up using [18F]FPEB-PET scans, categorizing patients based on response. Results showed a global decrease in mGluR5 availability in MDD patients versus controls at baseline. Post-treatment, remitters exhibited a significant increase in mGluR5 availability in the dorsolateral and ventromedial prefrontal cortex (Cohen’s d = 2.33 and 4.27). These findings underscore mGluR5's key role in MDD pathophysiology and treatment. The post-treatment increase in mGluR5 in key brain areas among remitters suggests its potential as a novel therapeutic target for MDD.