Nitric oxide plasma/serum levels in patients with schizophrenia: a systematic review and meta-analysis

João Paulo Maia-de-Oliveira, Clarissa Trzesniak, Irismar R Oliveira, Matthew J Kempton, Tatiana M N de Rezende, Sandro Iego, Glen B Baker, Serdar M Dursun, João Paulo Machado-de-Sousa, Jaime E C Hallak

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


For the last 40 years, schizophrenia has been considered to be the result primarily of a dysfunction in brain dopaminergic pathways. In this review, it is described and discussed findings concerning nitric oxide-mediated neurotransmission in schizophrenia. Studies were searched in PubMed, SciELO, and LILACS using the terms schizophrenia and nitric oxide plasma levels or nitric oxide serum levels, with no time limit. The reference lists of selected articles were also hand-searched for additional articles. From 15 potential reports, 10 were eligible to be included in the review and meta-analysis. These studies included a total of 505 patients with schizophrenia and 339 healthy volunteers. No significant difference was found between patients and healthy controls regarding total nitrite plasma/serum levels (effect size g = 0.285, 95%CI = -0.205 to 0.774, p = 0.254). However, when studies with patients under antipsychotic treatment were examined separately, there was a significant difference between patients and healthy volunteers (effect size g = 0.663, 95%CI = 0.365 to 0.961, p <0.001), showing that patients under treatment have higher levels of plasma/serum nitric oxide than controls. These results suggest that antipsychotics increase nitric oxide plasma/serum levels and that the nitrergic pathway would be a fertile target for the development of new treatments for patients with schizophrenia.
Original languageEnglish
Pages (from-to)S149-55
Number of pages7
JournalRevista brasileira de psiquiatria (São Paulo, Brazil : 1999)
Issue numberSuppl 2
Publication statusPublished - Oct 2012


  • Schizophrenia
  • Nitric Oxide
  • Empirical Research
  • Humans
  • Data Interpretation, Statistical
  • Antipsychotic Agents


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