Decreased expression of heme oxygenase is associated with depressive symptoms and may contribute to depressive and hypertensive comorbidity

Background: There is strong evidence that hypertension and depression are comorbid and oxidative stress is implicated in both pathologies. We aimed to elucidate the relationship between biochemical markers of the antioxidant-pro-oxidant equilibrium and depression in hypertension.

Methods: Blood was collected from patients diagnosed with depression, hypertension, or comorbid depression and hypertension and healthy age- and sex-matched controls. Whole blood reduced glutathione, erythrocyte superoxide dismutase (SOD-1), glutathione peroxidase (GPx-1), glutathione reductase (GR), malondialdehyde (MDA), and plasma hydrogen peroxide (H₂O₂) were assayed using spectrophotometry, and heme oxygenase (HO-1) levels were determined immunoenzymatically.

Results: Both hypertension and depression were associated with altered antioxidant-pro-oxidant profiles. Decreased GPx-1 and SOD-1 activities, increased GR activity, increased levels of GSH, and increased concentrations of MDA and H₂O₂ were observed in patients compared to controls. Inducible HO-1 was specifically decreased in patients with depression and was significantly associated with both the prevalence and severity of depressive symptoms.

Conclusions: Heme oxygenase is a biological factor that might explain the relationship between inflammation, oxidative stress, and the biological and functional changes in brain activity in depression. HO-1 is a candidate depression biomarker and provides an avenue for novel preventative and diagnostic strategies against this disease.