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

Downloads

Published

2024-03-22

DOI:

https://doi.org/10.55229/ijbs.v27i1.04

Keywords:

Oxidative stress, Schizophrenia, nitric oxide synthase, neutrophils

Dimensions Badge

Issue

Vol. 27 No. 01 (2024): Indian Journal of Behavioural Sciences

Section

RESEARCH ARTICLE

License

Copyright (c) 2024 Shashwat Saxena, Abhishek K Singh, Madhu Dikshit, Amit Singh, Manu Agarwal, Pronob K Dalal

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

You are free to:

  • The licensor cannot revoke these freedoms as long as you follow the license terms.

Under the following terms:

  • No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Crossref
Scopus
Google Scholar
Europe PMC

Authors

  • Shashwat Saxena Mind Wellness Clinic, Lucknow, Uttar Pradesh, India
  • Abhishek K Singh Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
  • Madhu Dikshit Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
  • Amit Singh King George Medical University, Lucknow, Uttar Pradesh, India
  • Manu Agarwal King George Medical University, Lucknow, Uttar Pradesh, India
  • Pronob K Dalal King George Medical University, Lucknow, Uttar Pradesh, India

Abstract

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.

How to Cite

Saxena, S., Singh, A. K., Dikshit, M., Singh, A., Agarwal, M., & Dalal, P. K. (2024). Neutrophil and Plasma Nitrite Levels and Neuronal Nitric Oxide Synthase Expression in Schizophrenia: A Case-Control Study. Indian Journal of Behavioural Sciences, 27(01), 23–31. https://doi.org/10.55229/ijbs.v27i1.04

Downloads

Download data is not yet available.

References

Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull 2018;44(6):1195–203.

Sawa A, Snyder SH. Schizophrenia: diverse approaches to a complex disease. Science 2002;296(5568):692–5.

Lai CY, Scarr E, Udawela M, Everall I, Chen WJ, Dean B. Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics. World J Psychiatry 2016;6(1):102–17.

Murray AJ, Rogers JC, Katshu MZUH, Liddle PF, Upthegrove R. Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders. Frontiers in Psychiatry [Internet] 2021 [cited 2023 Feb 26];12. Available from: https://www.frontiersin.org/articles/10.3389/fpsyt.2021.703452

Berg D, Youdim MBH, Riederer P. Redox imbalance. Cell Tissue Res 2004;318(1):201–13.

Yilmaz N, Herken H, Cicek HK, Celik A, Yürekli M, Akyol O. Increased levels of nitric oxide, cortisol and adrenomedullin in patients with chronic schizophrenia. Med Princ Pract 2007;16(2):137–41.

Nakano Y, Yoshimura R, Nakano H, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, et al. Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia: a pilot study. Hum Psychopharmacol 2010;25(2):139–44.

Herken H, Uz E, Ozyurt H, Söğüt S, Virit O, Akyol O. Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol Psychiatry 2001;6(1):66–73.

Suzuki E, Nakaki T, Nakamura M, Miyaoka H. Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia. J Psychiatry Neurosci 2003;28(4):288–92.

Zoroglu SS, Herken H, Yürekli M, Uz E, Tutkun H, Savaş HA, et al. The possible pathophysiological role of plasma nitric oxide and adrenomedullin in schizophrenia. J Psychiatr Res 2002;36(5):309–15.

Lee BH, Kim YK. Reduced plasma nitric oxide metabolites before and after antipsychotic treatment in patients with schizophrenia compared to controls. Schizophr Res 2008;104(1–3):36–43.

Flatow J, Buckley P, Miller BJ. Meta-Analysis of Oxidative Stress in Schizophrenia. Biol Psychiatry 2013;74(6):400–9.

Wallerath T, Gath I, Aulitzky WE, Pollock JS, Kleinert H, Förstermann U. Identification of the NO synthase isoforms expressed in human neutrophil granulocytes, megakaryocytes and platelets. Thromb Haemost 1997;77(1):163–7.

Kelley JB, Anderson KL, Altmann SL, Itzhak Y. Long-term memory of visually cued fear conditioning: roles of the nNOS gene and CREB. Neuroscience 2011;174:91–103.

Kelley JB, Anderson KL, Itzhak Y. Pharmacological modulators of nitric oxide signaling and contextual fear conditioning in mice. Psychopharmacology (Berl) 2010;210(1):65–74.

Ota KT, Pierre VJ, Ploski JE, Queen K, Schafe GE. The NO-cGMP-PKG signaling pathway regulates synaptic plasticity and fear memory consolidation in the lateral amygdala via activation of ERK/MAP kinase. Learn Mem 2008;15(10):792–805.

Baba H, Suzuki T, Arai H, Emson PC. Expression of nNOS and soluble guanylate cyclase in schizophrenic brain. Neuroreport 2004;15(4):677–80.

Tang W, Huang K, Tang R, Zhou G, Fang C, Zhang J, et al. Evidence for association between the 5’ flank of the NOS1 gene and schizophrenia in the Chinese population. Int J Neuropsychopharmacol 2008;11(8):1063–71.

Cui H, Nishiguchi N, Yanagi M, Fukutake M, Mouri K, Kitamura N, et al. A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain. Schizophr Res 2010;121(1–3):172–8.

Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, et al. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 2003;35(7):790–6.

World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization; 1992.

World Health Organization. Division of Mental Health. Schedules for clinical assessment in neuropsychiatry: version 2 [Internet]. American Psychiatric Press; 1994 [cited 2022 Feb 27]. Available from: https://apps.who.int/iris/handle/10665/40356

Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13(2):261–76.

APA. Diagnostic and Statistical Manual Mental Disorders (Fourth Edition) DSM-IV. Washington (DC): American Psychiatric Association; 1994.

Jacob KS, Bhugra D, Mann AH. General Health Questionnaire - 12: Psychometric Properties and Factor Structure Among Indian Women Living in the United Kingdom. Indian J Psychiatry 1997;39(3):196–9.

Sethi S, Singh MP, Dikshit M. Nitric oxide-mediated augmentation of polymorphonuclear free radical generation after hypoxia-reoxygenation. Blood 1999;93(1):333–40.

Aksoy H, Aksoy Y, Akçay F, Kurtul N. Estradiol and nitric oxide in men over 50 years of age. Int Urol Nephrol 2000;32(1):81–3.

Bryan NS. Nitrite in nitric oxide biology: cause or consequence? A systems-based review. Free Radic Biol Med 2006;41(5):691–701.

Kanabrocki EL, George M, Hermida RC, Messmore HL, Ryan MD, Ayala DE, et al. Day-night variations in blood levels of nitric oxide, T-TFPI, and E-selectin. Clin Appl Thromb Hemost 2001;7(4):339–45.

Smith DA, Hoffman AF, David DJ, Adams CE, Gerhardt GA. Nicotine-evoked nitric oxide release in the rat hippocampal slice. Neurosci Lett 1998;255(3):127–30.

Guarner C, Soriano G, Tomas A, Bulbena O, Novella MT, Balanzo J, et al. Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology 1993;18(5):1139–43.

Moncada S. Nitric oxide: discovery and impact on clinical medicine. J R Soc Med 1999;92(4):164–9.

Yanik M, Vural H, Tutkun H, Zoroğlu SS, Savaş HA, Herken H, et al. The role of the arginine-nitricoxide pathway in the pathogenesis of bipolar affectivedisorder. European Archives of Psychiatry and Clinical Neurosciences 2004;254(1):43–7.

Srivastava N, Barthwal MK, Dalal PK, Agarwal AK, Nag D, Srimal RC, et al. Nitrite content and antioxidant enzyme levels in the blood of schizophrenia patients. Psychopharmacology (Berl) 2001;158(2):140–5.

Bernstein HG, Krell D, Braunewell KH, Baumann B, Gundelfinger ED, Diekmann S, et al. Increased number of nitric oxide synthase immunoreactive Purkinje cells and dentate nucleus neurons in schizophrenia. J Neurocytol 2001;30(8):661–70.

Karson CN, Griffin WS, Mrak RE, Husain M, Dawson TM, Snyder SH, et al. Nitric oxide synthase (NOS) in schizophrenia: increases in cerebellar vermis. Mol Chem Neuropathol 1996;27(3):275–84.

Wratten NS, Memoli H, Huang Y, Dulencin AM, Matteson PG, Cornacchia MA, et al. Identification of a schizophrenia-associated functional noncoding variant in NOS1AP. Am J Psychiatry 2009;166(4):434–41.

Das I, Khan NS, Puri BK, Hirsch SR. Elevated endogenous nitric oxide synthase inhibitor in schizophrenic plasma may reflect abnormalities in brain nitric oxide production. Neurosci Lett 1996;215(3):209–11.

Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. European Heart Journal 2012;33(7):829–37.

Broadbelt K, Jones LB. Evidence of altered calmodulin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex. J Psychiatr Res 2008;42(8):612–21.

Zhilyaeva TV, Kasyanov ED, Semennov IV, Rukavishnikov GV, Piatoikina AS, Kostina OV, et al. Tetrahydrobiopterin deficiency in schizophrenia: Biochemical and clinical aspects. J Psychiatr Res 2022;153:141–8.

Mahadik SP, Mukherjee S. Free radical pathology and antioxidant defense in schizophrenia: a review. Schizophrenia Research 1996;19(1):1–17.

Most read articles by the same author(s)