Brain glutamate and gamma-aminobutyric acid levels across COVID-19 lockdowns in patients with recurrent major depressive disorder and healthy individuals

Abstract The coronavirus disease 2019 (COVID-19) led to substantial social restriction measures. Social isolation has been demonstrated to promote psychiatric symptoms and to dysregulate gamma-aminobutyric acid (GABA) and glutamate levels. The aim of this investigation was to observe brain GABA and...

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Main Authors: Valentin Popper, Benjamin Spurny-Dworak, Jakob Unterholzner, Murray Reed, Theresa Wechsler, Alexander Kautzky, Peter Stöhrmann, Manfred Klöbl, Andreas Mühlberger, Richard Frey, Dan Rujescu, Rupert Lanzenberger, Thomas Vanicek
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-05734-2
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Summary:Abstract The coronavirus disease 2019 (COVID-19) led to substantial social restriction measures. Social isolation has been demonstrated to promote psychiatric symptoms and to dysregulate gamma-aminobutyric acid (GABA) and glutamate levels. The aim of this investigation was to observe brain GABA and glutamate concentrations and depressive symptom severity in association to lockdowns in patients with recurrent major depression disorder (rMDD) and healthy individuals (HI). In this longitudinal study, 18 patients with rMDD (11 female: 37.0 ± 10.0years) and 28 HI (16 female, 28.1 ± 5.0years) underwent three magnetic resonance spectroscopy imaging (MRSI) measurements over multiple lockdowns. Ratios of GABA+ (GABA + macromolecules) and glutamate + glutamine (Glx) to total creatinine (tCr) as well as GABA+/Glx ratios were calculated for subcortical regions and the insula. Depressive symptom severity and social support were assessed at each visit. Lockdowns did not significantly change neurotransmitter ratios in individual brain regions (all p corrected > 0.05). Further, no significant changes in Beck’s Depression Inventory II (BDI-II) scores occurred along the lockdowns (all p corrected > 0.05). Our results may be explained by ceiling effects of the beginning of the pandemic and the first lockdown, by good social support during the pandemic in HI and a small sample size. Patients with rMDD reported an insufficient social support, suggesting a special vulnerability to social isolation due to pandemics.
ISSN:2045-2322