A Meta-Analysis of Magnetic Resonance Spectroscopy Studies on Glutamatergic Neurometabolite Levels in Major Depressive Disorder

Abstract

Glutamatergic neurometabolite dysregulation has recently garnered attention in the pathophysiology of major depressive disorder (MDD). However, studies have reported heterogeneous results for changes in neurometabolite levels across brain regions and whether these changes are related to antidepressant intervention. Herein, we performed a meta-analysis to investigate consistent findings by searching PubMed, Embase, MEDLINE, PsycINFO, and SinoMed from the start date of these databases to May 2023 (PROSPERO#CRD42023405205). Among the 2529 publications screened, 55 studies were included in the meta-analysis, with 1400 MDD patients and 1322 healthy controls. The results revealed significant decreases in Glx (glutamate + glutamine) in the anterior cingulate cortex (ACC) and prefrontal cortex (PFC), glutamate in the ACC and γ-aminobutyric acid in the occipital cortex in MDD patients compared with healthy controls. However, changes in neurometabolite levels from pre to posttherapeutic-intervention in MDD patients were not significant. Heterogeneity was moderate-to-high across all neurotransmitters and brain regions. Nonetheless, these findings inform current translation efforts for MDD research.