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 (HS) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of HS 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 HS and Hcy, and data were correlated to determine their potential as plasma biomarkers.

Results: Cross-sectional analyses revealed PSDs to have a low plasma HS level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of HS and Hcy in PSDs. Plasma levels of HS 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 HS and Hcy and expression of the TNF gene (i.e., HS-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents.

Conclusion: Plasma levels of HS and Hcy reflect changes in psychopathology and cognitive function in depression and HS-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.