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Cited by 28Treatment of Major DepressionTryptophan and brain disordersAdvanced MRI Techniques and Applications

Glutathione alterations in depression: a meta-analysis and systematic review of proton magnetic resonance spectroscopy studies

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Bell, Charles J. M., Mehta, Mitul, Mirza, Luwaiza, Young, Allan H., Beck, Katherine·2025·Psychopharmacology
DOI 10.1007/s00213-024-06735-1PMC PMC11890406
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Abstract

Background: Major depressive disorder (MDD) is a common and serious psychiatric disorder associated with significant morbidity. There is mounting evidence for the role of oxidative stress in the pathophysiology of depression. Objective: To investigate alterations in the brain antioxidant glutathione in depression by undertaking a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS). Methods: MEDLINE, EMBASE and Psych Info databases were searched for case–control studies that reported brain glutathione levels in patients with depression and healthy controls. Means and variances (SDS) were extracted for each measure to calculate effect sizes. Hedges g was used to quantify mean differences. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Results: 8 studies that reported measurements for 230 patients with depression and 216 controls were included. Three studies included data for the occipital cortex and five studies for the medial frontal cortex. In the occipital cortex, GSH was lower in the patient group as compared to controls (g = -0.98, 95% [CI, -1.45—-0.50], P = < 0.001). In both the medial frontal cortex and in the combined all areas analysis there was no significant difference in GSH levels between cases and controls. Conclusions: This study found reduced levels of GSH specifically in the occipital region of patients with MDD. This provides some support for the role of oxidative stress in depression and suggests that targeting this system may provide future therapeutic opportunities. However, the meta-analysis was limited by the small number and quality of the included studies. More studies using high quality MRS methods in a variety of brain regions are needed in the future to test this putative hypothesis.

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  • Oxidative stress and alterations in the GSH metabolism of the brain have been connected with many neurological and neurodegenerative diseases.

    “Oxidative stress and alterations in the GSH metabolism of the brain have been connected with many neurological and neurodegenerative diseases as recently summarized (Asanuma and Miyazaki 2021; Bell et al. 2024; Bjørklund et al. 2021, 2020; Bottino et al. 2021; Iskusnykh et al. 2022; Kim 2021; Murray et al. 2024).”

    From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Bell et al. 2024

    The Discussion links reduced brain GSH and oxidative stress to major depressive disorder, and discusses a separate finding in bipolar disorder. It does not establish the broader claim about many neurological and neurodegenerative diseases; the cited passages focus on mood disorders. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Bell, C. J. M., Mehta, M., Mirza, L., Young, A. H., & Beck, K.
Affiliations
King's College London (GB)
Corresponding author
Bell, Charles J. M.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2024-12-21
Volume
242
Issue
4
Pages
717-724
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-024-06735-1
PMC
PMC11890406
OpenAlex
W4405655647
Cited by
28
References
6
Citations by year
2026: 19 · 2025: 9
FWCI
1.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychopharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • Rosetrees Trust
  • Stoneygate Trust
  • National Institute for Health and Care Research
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
major depressive disorder, glutathione, oxidative stress, 1H NMR, occipital cortex, medial frontal cortex
MeSH terms
Brain, Major Depressive Disorder, Glutathione, Humans, Occipital Lobe, Oxidative Stress, Proton Magnetic Resonance Spectroscopy

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