Changes in plasma hydrogen sulfide are associated with cognitive improvements in schizophrenia patients treated with atypical antipsychotics

Background Hydrogen sulfide (H₂S) acts as a neuromodulator in the brain and is shown to be associated with cognitive impairments in schizophrenia. Atypical antipsychotics can provide cognitive benefits for schizophrenia patients. This prospective observational study aims to investigate whether H 2 S signaling is involved in the cognitive improvement effects of atypical antipsychotics in patients with schizophrenia. Methods A total of 25 schizophrenia patients with acute exacerbation who completed follow-up and 28 healthy controls were included in this study. Psychopathological symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and a neuropsychological test battery, respectively. Plasma H 2 S levels were determined using high-performance liquid chromatography (HPLC). Results We found that compared with normal controls, schizophrenia patients exhibited poorer cognitive function and lower plasma H 2 S levels at baseline ( p < 0.05). After two months of atypical antipsychotic treatment, the patients showed significant improvements in processing speed, working memory, visuospatial memory, attention, and executive function (all p < 0.01). At the same time, plasma H 2 S levels in patients after treatment were significantly elevated compared to baseline (0.918 ± 0.036 vs. 0.712 ± 0.023 µmol/L; t = 6.807, p < 0.001). Correlation analysis revealed that the increase in H 2 S was significantly associated with improvements in working memory (r = 0.291, p = 0.005) and visuospatial memory (r = 0.227, p = 0.016). Conclusion Our findings demonstrated that cognitive improvement in patients with schizophrenia after treatment with atypical antipsychotics is correlated with an increase of plasma H₂S levels, suggesting that H 2 S signaling is involved in the pathophysiological process of cognitive impairment in schizophrenia.