Neutrophil and Plasma Nitrite Levels and Neuronal Nitric Oxide Synthase Expression in Schizophrenia: A Case-Control Study

Background: In neural tissues, neuronal nitric oxide synthase (nNOS) primarily leads to nitric oxide (NO) synthesis which acts as a neurotransmitter. NO is also an oxidant produced during oxidative stress states and has been implicated in the etiopathogenesis of schizophrenia. Thus, it can be a potential biomarker of schizophrenia.Aims: In this study, we aimed to determine the differences in the levels of nNOS (in circulating neutrophil) and nitrite (in circulating neutrophil and plasma) in the drug naïve or drug-free patients of first-episode schizophrenia, their first-degree relatives (FDR) and healthy controls (HC).Methods: Drug-free adults with schizophrenia, and age and sex-matched FDRs, and HCs were tested for nNOS expression (in circulating neutrophil) and nitrite levels (in circulating neutrophil and plasma). Kruskal Wallis H test was used to compare continuous variables.Results: The final sample consisted of 31 participants in each group. The nNOS expression was significantly higher in schizophrenia patients compared to FDRs and HCs. In patients the plasma and neutrophil nitrite levels were significantly lower compared to HCs, but not FDRs. The nNOS expression among FDRs was also significantly higher compared to HCs. There was no correlation among nNOS expression, plasma nitrite level, and neutrophil nitrite level.Conclusions: Plasma and neutrophil nitrite could be potential trait markers for schizophrenia. There is no straightforward association between nNOS expression, and nitrite levels in plasma and circulating neutrophils.