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

Objective: Hydrogen sulfide (H ₂ S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H ₂ S 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 H ₂ S and Hcy, and data were correlated to determine their potential as plasma biomarkers.
Results: Cross-sectional analyses revealed PSDs to have a low plasma H ₂ S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H ₂ S and Hcy in PSDs. Plasma levels of H ₂ S 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 H ₂ S and Hcy and expression of the TNF gene (i.e., H ₂ S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents.
Conclusion: Plasma levels of H ₂ S and Hcy reflect changes in psychopathology and cognitive function in depression and H ₂ S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
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