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

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.