Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis / chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression

Neuro Endocrinol Lett. 2011;32(2):133-40.


Background: Major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are two disorders accompanied by an upregulation of the inflammatory and oxidative and nitrosative (IO&NS) pathways and a decreased antioxidant status. Moreover, depression is accompanied by disorders in inflammatory and neuroprogressive (IN-PRO) pathways.

Methods: This study examines whole blood glutathione peroxidase (GPX) in depression and in ME/CFS; GPX is an enzyme that reduces hydroperoxides by oxidizing glutathione and consequently protects the cells from oxidative damage. Blood was sampled in 39 patients with depression, 40 patients with ME/CFS and 24 normal volunteers. Whole blood was analysed for GPX activity using the Ransel assay (Randox). Severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF scale).

Results: We found that whole blood GPX activity was significantly (p=0.001) lower in depressed patients than in normal controls and that there were no significant differences between ME/CFS and controls. In depression and ME/CFS, there were significant and inverse relationships between GPX activity and the FF items, depressed mood and autonomic symptoms. In depression, there were significant and negative correlations between whole blood GPX and the HDRS score and autonomic symptoms.

Discussion: The results show that lowered whole blood GPX activity contributes to the lowered antioxidant status in depression. Since GPX activity is a predictor of neuroprogression and coronary artery disease (CAD), lowered GPX activity in depression contributes to the IN-PRO pathways and the comorbidity between depression and CAD. Our results suggest that patients with depression would benefit from Ebselen or a supplementation with glutathione, N-Acetyl-l-Cysteine and selenium.

MeSH terms

  • Adult
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Case-Control Studies
  • Comorbidity
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / physiopathology*
  • Depression / blood*
  • Depression / epidemiology
  • Depression / physiopathology*
  • Disease Progression
  • Fatigue Syndrome, Chronic / blood*
  • Fatigue Syndrome, Chronic / physiopathology
  • Female
  • Glutathione Peroxidase / blood*
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Signal Transduction / physiology*


  • Antioxidants
  • Biomarkers
  • Glutathione Peroxidase