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Abnormalities in nitric oxide synthase system function and their association with cognitive function in first-episode
Fei Jiang1, Jie Hou2, Qun Yang1
1Department of Psychiatry, Nantong Mental Health Center, The Fourth People's Hospital of Nantong, Nantong, P. R. China.
Schizophrenia (Heidelberg, Germany)
|May 12, 2026
Summary
Nitric oxide synthase (NOS) system dysfunction is present in early schizophrenia, impacting cognitive function. Overall NOS activity, not specific subtypes, is linked to cognitive deficits and partly independent of symptom severity.
Area of Science:
- Neuroscience
- Psychiatry
- Biochemistry
Background:
- Cognitive deficits are a hallmark of schizophrenia, significantly affecting patient outcomes.
- The role of the nitric oxide (NO) signaling pathway in early, drug-naïve schizophrenia is not well understood.
Purpose of the Study:
- To investigate the relationship between the nitric oxide synthase (NOS) system and cognitive function in first-episode, drug-naïve schizophrenia patients.
- To explore the association between NOS markers, cognitive performance, and symptom severity.
Main Methods:
- Studied 98 first-episode, drug-naïve schizophrenia patients and 96 healthy controls.
- Measured plasma levels of inducible NOS (iNOS), total NOS (TNOS), iNOS/TNOS ratio, malondialdehyde (MDA), and hydrogen peroxide (H₂O₂).
- Assessed psychopathology with the Positive and Negative Syndrome Scale (PANSS) and cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Main Results:
- Schizophrenia patients showed NOS system dysfunction: reduced iNOS and TNOS, lower iNOS/TNOS ratio, elevated MDA, and reduced H₂O₂.
- Total NOS (TNOS) levels positively correlated with overall cognitive performance (RBANS) and specific domains, independent of symptom severity (PANSS).
- Inducible NOS (iNOS) levels were linked only to immediate memory; the iNOS/TNOS ratio showed no independent cognitive association.
Conclusions:
- Early schizophrenia is characterized by significant dysfunction in the NOS system.
- Overall NOS activity, rather than specific subtype expression (iNOS/TNOS ratio), is closely associated with cognitive impairment in schizophrenia.
- NOS system function reflects disease burden and is partly independent of psychopathological symptom severity.
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