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

## TL;DR

This study examined brain glutamate and GABA levels in people with depression and healthy individuals during lockdowns, finding no significant changes in neurotransmitter levels or depressive symptoms.

## Contribution

The study provides longitudinal insights into the effects of pandemic-related lockdowns on brain chemistry and depression symptoms.

## Key findings

- Lockdowns did not significantly alter brain GABA or glutamate levels in either group.
- Depressive symptom severity remained stable across lockdowns.
- Patients with rMDD reported insufficient social support, indicating vulnerability to isolation.

## 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 pcorrected > 0.05). Further, no significant changes in Beck’s Depression Inventory II (BDI-II) scores occurred along the lockdowns (all pcorrected > 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.

The online version contains supplementary material available at 10.1038/s41598-025-05734-2.