ArticlePsychoradiology2026
γ-Aminobutyric acid and glutamate dysregulation in the dorsolateral prefrontal cortex of adolescents with first-episode major depressive disorder and the modulatory effects of repetitive transcranial magnetic stimulation.
Article in Psychoradiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Major depressive disorder (MDD) is associated with dysregulation of γ-aminobutyric acid (GABA) and glutamate(Glu) neurotransmission in the prefrontal cortex. Proton magnetic resonance spectroscopy (1H-MRS) enables non-invasive in vivo quantification of GABA and Glx(glutamate + glutamine) levels. This study investigated neurochemical characteristics of the bilateral dorsolateral prefrontal cortex (DLPFC) in first-episode adolescent MDD (FEA-MDD) and repetitive transcranial magnetic stimulation (rTMS)'s impact on these changes. Methods: 42 drug-naïve FEA-MDD patients underwent bilateral DLPFC MRS scans before and after rTMS, with 42 healthy controls (HCs) as baseline. All participants were right-handed. The Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) protocol detected GABA+ (GABA plus macromolecules and high carnosine) and Glx levels, processed via Gannet software. Results: FEA-MDD patients exhibited significantly lower GABA+ and higher Glx levels in the left DLPFC than HCs; in the right DLPFC, no significant difference in GABA+ levels was observed, though Glx levels were elevated. After rTMS treatment, GABA+ levels in the left DLPFC increased significantly, whereas Glx levels showed a non-significant decreasing trend. Additionally, HCs had no hemispheric differences, while in FEA-MDD, the left DLPFC showed lower GABA+ and Glx levels compared to the right. We also found that in the left DLPFC, baseline GABA+ levels were negatively correlated with Hamilton Depression Scale (HAMD) scores; Glx levels showed positive correlations with scores on the Ruminative Response Scale (RRS), Self-Rating Depression Scale (SDS), and Self-Esteem Scale (SES). Conclusions: FEA-MDD involves prefrontal GABA+/Glx dysregulation, and rTMS may aid in restoring neurotransmitter balance within the DLPFC. This study adds to the expanding body of evidence supporting the application of targeted neurochemical modulation in the treatment of FEA-MDD, while also providing insights into potential intervention mechanisms.
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