Preview

V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY

Advanced search

Association of hematological coefficients with markers of inflammation and oxidative stress in schizophrenia: results of a pilot analysis

https://doi.org/10.31363/2313-7053-2025-3-1083

Abstract

Relevance. To date, there is convincing evidence in favour of the immuno-inflammatory hypothesis of the etiopathogenesis of schizophrenia. As markers of immuno-inflammatory disorders in schizophrenia, a small number of studies have examined haematological indices (HI) and systemic inflammation coefficients (SIC): neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) and platelet-lymphocyte ratio (PLR). Considering that HI may hypothetically reflect immuno-inflammatory processes in schizophrenia, it is relevant to assess their relationship with other known biochemical markers of inflammation and oxidative stress in this disease. The aim of this study was to evaluate the association of HI with biochemical markers of inflammation and oxidative stress in schizophrenia, as well as with the severity of clinical symptoms. Materials and methods: 50 patients with schizophrenia were examined: 42 women, 8 men, age 36 [7] years (median and interquartile range, hereafter Me [Q1; Q3]). Clinical assessment was performed using the Schizophrenia Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. HI, homocysteine (Hc), tetrahydrobioterine (BH4), reduced glutathione (GSH), interleukin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-a) were studied. Results: Serum CRP levels were significantly correlated with leukocyte count, total monocyte, basophil and eosinophil counts, and granulocyte counts, but not with SIC (NLP, MLR and PLR). TNF-a has stronger direct correlations with a number of HI (granulocyte and erythrocyte counts, leukocyte counts at the level of trend towards significance) and coefficients (NLP, MLR at the level of trend). Conclusions: HI in the studied sample of patients with schizophrenia correlate with the data obtained by foreign authors, which indicates the prospect of studying this topic in the Russian population. Further evaluation of the relationship between HI (SIC) and serum TNF-a seems relevant. The study of associations of biochemical immuno-inflammatory markers with SIC further requires a thorough assessment of the stage of disease development, duration of its course, peculiarities of response to therapy.

About the Authors

Zhakhongir A.u. Abdumannonov
Privolzhsky Research Medical University
Russian Federation

Nizhny Novgorod



Ilya S. Blokhin
Privolzhsky Research Medical University
Russian Federation

Nizhny Novgorod



Alexandra Yu. Kargina
Privolzhsky Research Medical University
Russian Federation

Nizhny Novgorod



Alexandra A. Demidova
P.P. Kashchenko Regional Psychoneurological Hospital № 1
Russian Federation

Nizhny Novgorod



Olga V. Kostina
Privolzhsky Research Medical University
Russian Federation

Nizhny Novgorod



Tatiana V. Zhilyaeva
Privolzhsky Research Medical University; V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation

Nizhny Novgorod; St. Petersburg



Galina E. Mazo
V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology
Russian Federation

St. Petersburg



References

1. Golimbet VE, Klushnik TP. Molecular-genetic and immunological aspects of the formation of psychopathological symptomatology in schizophrenia. Nevrologiya i povedencheskaya fiziologiya. 2023;53(5):812-817. (In Russ.). https://doi.org/10.1007/s11055-023-01473-x;

2. Gorbunova AP, Rukavishnikov GV, Kasyanov ED, Mazo GE. The role of hematological coefficients of systemic inflammation in the diagnosis and risk assessment of affective disorders. Obozrenie psihiatrii i medicinskoj psihologii imeni V.M. Bekhtereva. 2024;58(1):47-55. (In Russ.). https://doi.org/10.31363/2313-7053-2024-794

3. Zhilyaeva TV, Rukavishnikov GV, Manakova EA, Mazo GE. Serum Interleukin-6 in Schizophrenia: Associations with Clinical and Sociodemographic Characteristics. Consortium Psychiatricum. 2023;4(4):5-16. (In Russ.). https://doi.org/10.17816/CP11067

4. Zozulya SA, Othman IN, Anikhovskaya IA, Tikhonov DV, Kaleda VG, Yakovlev MYu, Klyushnik TP. Inflammatory markers and indicators of systemic endotoxaemia in patients with treatment-resistant schizophrenia. European Psychiatry. 2023;66(1):247-248. https://doi.org/10.1192/j.eurpsy.2023.568

5. Zozulya SA, Sarmanova ZV, Otman IN, Klyushnik TP. Markers of inflammation in schizophrenia for science and practice. Doktor.Ru. 2023;22(6):7-14. (In Russ.). https://doi.org/10.31550/1727-2378-2023-22-6-7-14;

6. Klyushnik TP, Smulevich AB, Zozulya SA, Romanov DV, Lobanova VM. Clinical and Immunological Aspects of Delusional Disorders in Paranoid Schizophrenia. Psikhiatriya. 2023;21(2):6-16. (In Russ.). https://doi.org/10.30629/2618-6667-2023-21-2-6-16

7. Rukavishnikov GV, Zhilyaeva TV, Dubinina EE, Mazo GE. Interleukin-6 Role in Schizophrenia Pathological Mechanisms. Nejrohimiya. 2023;40(1):23-29. (In Russ.). https://doi.org/10.31857/S1027813323010168

8. Sarkarova MR, Maevskaya MV. Prognostic and diagnostic value of the ratio of neutrophils to lymphocytes of patients with diseases of the gastrointestinal tract and liver. Meditsinskiy Sovet 2022;16(7):60–68. (In Russ.). https://doi.org/10.21518/2079-701X-2022-16-7-60-68

9. Addington D, Addington J, Maticka-Tyndale E. Assessing depression in schizophrenia: the Calgary Depression Scale. Br J Psychiatry Suppl. 1993;22:39-44

10. Ahmed AO, Strauss GP, Buchanan RW, Kirkpatrick B, Carpenter WT. Schizophrenia heterogeneity revisited: Clinical, cognitive, and psychosocial correlates of statistically-derived negative symptoms subgroups. J Psychiatr Res. 2018;97:8-15. https://doi.org/10.1016/j.jpsychires.2017.11.004

11. Borovcanin MM, Jovanovic I, Radosavljevic G et al. Interleukin-6 in Schizophrenia-Is There a Therapeutic Relevance?. Front Psychiatry. 2017;8:221. https://doi.org/10.3389/fpsyt.2017.00221

12. Buckley PF. Neuroinflammation and Schizophrenia. Curr Psychiatry Rep. 2019;21(8):72. https://doi.org/10.1007/s11920-019-1050-z

13. Çakici N, van Beveren NJM, Judge-Hundal G, Koola MM, Sommer IEC. An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis. Psychol Med. 2019;49(14):2307-2319. https://doi.org/10.1017/S0033291719001995

14. Do KQ, Trabesinger AH, Kirsten-Krüger M et al. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000;12(10):3721-3728. https://doi.org/10.1046/j.1460-9568.2000.00229

15. Farokhnia M, Azarkolah A, Adinehfar F et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013;36(6):185-192. https://doi.org/10.1097/WNF.0000000000000001

16. Flatow J, Buckley P, Miller BJ. Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry. 2013;74(6):400-409. https://doi.org/10.1016/j.biopsych.2013.03.018

17. Fond G, Lançon C, Auquier P, Boyer L. C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review. Front Psychiatry. 2018;9:392. https://doi.org/10.3389/fpsyt.2018.00392

18. Gökmen F, Akbal A, Reşorlu H, Gökmen E, Güven M, Aras AB, Erbağ G, Kömürcü E, Akbal E, Coşar M. Neutrophil-Lymphocyte Ratio Connected to Treatment Options and Inflammation Markers of Ankylosing Spondylitis. J Clin Lab Anal. 2015;29(4):294-8. https://doi.org/10.1002/jcla.21768

19. Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21(12):1696-1709. https://doi.org/10.1038/mp.2016.3

20. González-Blanco L, García-Portilla MP, García-Álvarez L, et al. Oxidative stress biomarkers and clinical dimensions in first 10 years of schizophrenia. Biomarcadores de estrés oxidativo y dimensiones clínicas en los 10 primeros años de esquizofrenia. Rev Psiquiatr Salud Ment (Engl Ed). 2018;11(3):130-140. https://doi.org/10.1016/j.rpsm.2018.03.003

21. Hsu MC, Huang YS, Ouyang WC. Beneficial effects of omega-3 fatty acid supplementation in schizophrenia: possible mechanisms. Lipids in health and disease. 2020;19(1):159. https://doi.org/10.1186/s12944-020-01337-0

22. Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia. Schizophrenia Bulletin. 1987;13(2):261–276. https://doi.org/10.1093/schbul/13.2.261

23. Kirkpatrick B, Buchanan RW, Ross DE, Carpenter WT Jr. A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry. 2001;58(2):165-171. https://doi.org/10.1001/archpsyc.58.2.165

24. Kulaksizoglu B, Kulaksizoglu S. Relationship between neutrophil/lymphocyte ratio with oxidative stress and psychopathology in patients with schizophrenia. Neuropsychiatr Dis Treat. 2016;12:1999-2005. https://doi.org/10.2147/NDT.S110484

25. Levine J, Stahl Z, Sela BA et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 2006;60(3):265-269. https://doi.org/10.1016/j.biopsych.2005.10.009

26. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011;70(7):663-671. https://doi.org/10.1016/j.biopsych.2011.04.013

27. Miller BJ, Culpepper N, Rapaport MH. C-reactive protein levels in schizophrenia: a review and meta-analysis. Clin Schizophr Relat Psychoses. 2014;7(4):223-230. https://doi.org/10.3371/CSRP.MICU.020813

28. Özdin S, Böke Ö. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in different stages of schizophrenia. Psychiatry Res. 2019;271:131-135. https://doi.org/10.1016/j.psychres.2018.11.043

29. Özdin S, Sarisoy G, Böke Ö. A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review. Nord J Psychiatry. 2017;71(7):509-512.

30. Semiz M, Yildirim O, Canan F et al. Elevated neutrophil/lymphocyte ratio in patients with schizophrenia. Psychiatr Danub. 2014;26(3):220-225.

31. Sen BB, Rifaioglu EN, Ekiz O, Inan MU, Sen T, Sen N. Neutrophil to lymphocyte ratio as a measure of systemic inflammation in psoriasis. Cutan Ocul Toxicol. 2014;33(3):223-227. https://doi.org/10.3109/15569527.2013.834498

32. Steiner J, Frodl T, Schiltz K, Dobrowolny H, Jacobs R, Fernandes BS, Guest PC, Meyer-Lotz G, Borucki K, Bahn S, Bogerts B, Falkai P, Bernstein HG. Innate Immune Cells and C-Reactive Protein in Acute First-Episode Psychosis and Schizophrenia: Relationship to Psychopathology and Treatment. Schizophr Bull. 2020;46(2):363-373. https://doi.org/10.1093/schbul/sbz068

33. Steiner J, Guest PC, Rahmoune H, Martins-de-Souza D. The Application of Multiplex Biomarker Techniques for Improved Stratification and Treatment of Schizophrenia Patients. Methods Mol Biol. 2017;1546:19-35. https://doi.org/10.1007/978-1-4939-6730-8_2

34. Yilmaz H, Yalcin KS, Namuslu M, et al. Neutrophil-lymphocyte ratio (NLR) could be better predictor than C-reactive protein (CRP) for liver fibrosis in non-alcoholic steatohepatitis (NASH). Ann Clin Lab Sci. 2015;45:278–286

35. Yüksel RN, Ertek IE, Dikmen AU, Göka E. High neutrophil-lymphocyte ratio in schizophrenia independent of infectious and metabolic parameters. Nord J Psychiatry. 2018;72(5):336-340. https://doi.org/10.1080/08039488.2018.1458899

36. Zheng W, Cai DB, Yang XH, et al. Adjunctive celecoxib for schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials. J Psychiatr Res. 2017;92:139-146. https://doi.org/10.1016/j.jpsychires.2017.04.004

37. Zhilyaeva TV, Kasyanov ED, Rukavishnikov GV, Piatoikina AS, Bavrina AP, Kostina OV, Zhukova ES, Shcherbatyuk TG, Mazo GE. Pterin metabolism, inflammation and oxidative stress biochemical markers in schizophrenia: Factor analysis and assessment of clinical symptoms associations. Prog Neuropsychopharmacol Biol Psychiatry. 2023;127:110823. https://doi.org/10.1016/j.pnpbp.2023.110823

38. Zhou X, Tian B, Han HB. Serum interleukin-6 in schizophrenia: A system review and meta-analysis. Cytokine. 2021;141:155441. https://doi.org/10.1016/j.cyto.2021.155441

39. Zhu X, Zhou L, Li Q, Pan R, Zhang J, Cui Y. Combined score of C-reactive protein level and neutrophil-to-lymphocyte ratio: A novel marker in distinguishing children with exacerbated asthma. Int J Immunopathol Pharmacol. 2021;35:20587384211040641. https://doi.org/10.1177/20587384211040641


Review

For citations:


Abdumannonov Zh.A., Blokhin I.S., Kargina A.Yu., Demidova A.A., Kostina O.V., Zhilyaeva T.V., Mazo G.E. Association of hematological coefficients with markers of inflammation and oxidative stress in schizophrenia: results of a pilot analysis. V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY. (In Russ.) https://doi.org/10.31363/2313-7053-2025-3-1083

Views: 16


ISSN 2313-7053 (Print)
ISSN 2713-055X (Online)