Plasma levels of hydrogen sulfide and homocysteine correlate with the efficacy of antidepressant agents and serve as potential diagnostic and therapeutic markers

Abstract

Objective

Hydrogen sulfide (H₂S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H₂S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function.

Methods

Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H₂S and Hcy, and data were correlated to determine their potential as plasma biomarkers.

Results

Cross-sectional analyses revealed PSDs to have a low plasma H₂S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H₂S and Hcy in PSDs. Plasma levels of H₂S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H₂S and Hcy and expression of the TNF gene (i.e., H₂S–Hcy–TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents.

Conclusion

Plasma levels of H₂S and Hcy reflect changes in psychopathology and cognitive function in depression and H₂S–Hcy–TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.