Reduced plasma nitric oxide metabolites before and after antipsychotic treatment in patients with schizophrenia compared to controls

Schizophr Res. 2008 Sep;104(1-3):36-43. doi: 10.1016/j.schres.2008.06.005. Epub 2008 Jul 18.


Background: Nitric oxide (NO) is believed to have a role in the pathophysiology of schizophrenia. We examined plasma levels of NO metabolites in patients with schizophrenia and normal controls. We also determined the impact of 6-week risperidone treatment on circulating NO metabolites in patients with schizophrenia.

Method: Plasma NO metabolite (NO(x)) levels were measured in 55 schizophrenia patients before and after 6-week treatment with risperidone and in 55 normal controls. Severity of schizophrenia and response to treatment were assessed with the positive and negative syndrome scale (PANSS) for schizophrenia. NO(x) levels were estimated by the Griess method.

Results: Pre-treatment plasma NO(x) levels in schizophrenia patients (8.97+/-6.74 micromol/L) were lower than those of normal controls (14.51+/-6.30 micromol/L) (p<0.01). Schizophrenia patients had lower post-treatment NO(x) levels (10.99+/-8.31 micromol/L) than those of normal controls (p<0.01). There was marginal significant change between plasma NO(x) levels before and after 6-week treatment (p=0.056). Moreover, in 37 treatment responders (> or = 30% improvement in PANSS score), post-treatment plasma NO(x) significantly increased in comparison to pre-treatment NO(x) (p=0.028).

Conclusions: Plasma levels of NO(x) in patients with schizophrenia were significantly lower than normal controls both before and after the treatment. Our findings suggest that the improvement of psychiatric symptoms can lead to partially normalize a deficiency of NO after treatment in schizophrenia patients. Our findings support the hypothesis that the NO system is dampened in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Electrocardiography
  • Electroencephalography
  • Female
  • Humans
  • Male
  • Nitric Oxide / blood*
  • Risperidone / therapeutic use*
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology


  • Antipsychotic Agents
  • Nitric Oxide
  • Risperidone