Hydrogen sulfide and polysulfide levels in cerebrospinal fluid and plasma of patients with schizophrenia, Alzheimer’s disease, Parkinson’s disease, and in relation to cigarette smoking

Hydrogen sulfide (H ₂ S) and polysulfides produced by enzymes regulate neuronal transmission and protect neurons against oxidative stress. Abnormalities in their levels have been implicated in the pathophysiology of schizophrenia (SZ), Alzheimer’s disease (AD), and Parkinson’s disease (PD). However, the levels of these molecules in the cerebrospinal fluid (CSF) and plasma (PLA) obtained from the same individuals with or without smoking habits have yet to be comprehensively studied. Here, we showed that the levels of neuroprotective H ₂ S and polysulfides in the CSF were significantly decreased in patients with AD and SZ compared with those in control individuals, suggesting that neuronal activity is not well regulated and that neurons are inadequately protected in both diseases. In contrast, in PD, the levels of these molecules increase specifically in the PLA to unfavorable levels, suggesting peripheral abnormalities, including inflammation. The increased levels of these molecules in PD were restored by smoking habits to the levels in control non-smokers, suggesting that smoking may be linked to a lower risk of developing PD. H ₂ S and polysulfides play important roles in the pathophysiology of psychiatric and neurodegenerative diseases, and therefore, are potential therapeutic targets.