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

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 H₂S signaling is involved in the cognitive improvement effects of atypical antipsychotics in patients with schizophrenia.

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 H₂S levels were determined using high-performance liquid chromatography (HPLC).

We found that compared with normal controls, schizophrenia patients exhibited poorer cognitive function and lower plasma H₂S 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 H₂S 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 H₂S was significantly associated with improvements in working memory (r = 0.291, p = 0.005) and visuospatial memory (r = 0.227, p = 0.016).

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 H₂S signaling is involved in the pathophysiological process of cognitive impairment in schizophrenia.