Preview

Title

Advanced search

Inflammatory Markers in Schizophrenia Patients: Scientific and Practical Significance

https://doi.org/10.31550/1727-2378-2023-22-6-7-14

Abstract

Objective: To present literature data and results of own studies of inflammatory biomarkers identified in schizophrenia patients for diagnostic and forecasting purposes.

Key points. Special attention is paid to the medical technique called Neuroimmunotest developed at the Scientific Centre for Mental Health and its use in the study of schizophrenia pathogenesis, immune system status in various psychopathologic disorders, as well as for disease monitoring, forecasting and therapy efficiency assessment.

Conclusion. The literature data and results of own studies demonstrate the key role of immune mechanisms, primarily of inflammation, in the development of psychopathologic disorders in schizophrenia patients. Classification of schizophrenia patients not only on the basis of clinical manifestations, but also using the immune marker profile makes it possible to objectify their condition and forecast the efficiency of personified therapy; therefore, this approach is of interest for practical application in clinical psychiatry. 

About the Authors

S. A. Zozulya
Federal State Budgetary Scientific Institution «Mental Health Research Centre»
Russian Federation

34 Kashirskoye Highway, Moscow,  115522



Z. V. Sarmanova
Federal State Budgetary Scientific Institution «Mental Health Research Centre»
Russian Federation

34 Kashirskoye Highway, Moscow,  115522



I. N. Otman
Federal State Budgetary Scientific Institution «Mental Health Research Centre»
Russian Federation

34 Kashirskoye Highway, Moscow,  115522



T. P. Klyushnik
Federal State Budgetary Scientific Institution «Mental Health Research Centre»
Russian Federation

34 Kashirskoye Highway, Moscow,  115522



References

1. Barichello T., Simoes L.R., Quevedo J., Zhang X.Y. Microglial activation and psychotic disorders: evidence from pre-clinical and clinical studies. Curr. Top. Behav. Neurosci. 2020;44:161–205. DOI: 10.1007/7854_2018_81

2. Martos D., Tuka B., Tanaka M., Vécsei L. et al. Memory enhancement with kynurenic acid and its mechanisms in neurotransmission. Biomedicines. 2022;10(4):849. DOI: 10.3390/biomedicines10040849

3. Najjar S., Pearlman D.M., Alper K., Najjar A. et al. Neuroinflammation and psychiatric illness. J. Neuroinflammation. 2013;10:43. DOI: 10.1186/1742-2094-10-43

4. Ermakov E.A., Mednova I.A., Boiko A.S., Buneva V.N. et al. Chemokine dysregulation and neuroinflammation in schizophrenia: a systematic review. Int. J. Mol. Sci. 2023;24(3):2215. DOI: 10.3390/ijms24032215

5. Jeppesen R., Orlovska-Waast S., Sørensen N.V., Christensen R.H.B. et al. Cerebrospinal fluid and blood biomarkers of neuroinflammation and blood-brain barrier in psychotic disorders and individually matched healthy controls. Schizophr. Bull. 2022;48(6):1206–16. DOI: 10.1093/schbul/sbac098

6. Mostafa M., Elwasify M., Fathy A.A., Abdelsalam M. Toll-Like Receptor 4 gene polymorphisms and susceptibility to schizophrenia: a case-control study. Immunol. Invest. 2022;51(7):2009–24. DOI: 10.1080/08820139.2022.2093118

7. Müller N. Inflammation in schizophrenia: pathogenetic aspects and therapeutic considerations. Schizophr. Bull. 2018;44(5):973–82. DOI: 10.1093/schbul/sby024

8. Malashenkova I.K., Krynskiy S.A., Ogurtsov D.P., Mamoshina M.V. et al. A role of the immune system in the pathogenesis of schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(12):72–80. (in Russian). DOI: 10.17116/jnevro201811812172

9. Romeo B., Brunet-Lecomte M., Martelli C., Benyamina A. Kinetics of cytokine levels during antipsychotic treatment in schizophrenia: a meta-analysis. Int. J. Neuropsychopharmacol. 2018;21(9):828– 36. DOI: 10.1093/ijnp/pyy062

10. Zhang X.Y., Zhou D.F., Cao L.Y., Zhang P.Y. et al. Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J. Clin. Psychiatry. 2004;65(7):940–7. DOI: 10.4088/jcp.v65n0710

11. Dudzińska E., Szymona K., Bogucki J., Koch W. et al. Increased markers of oxidative stress and positive correlation low-grade inflammation with positive symptoms in the first episode of schizophrenia in drug-naïve patients. J. Clin. Med. 2022;11(9):2551. DOI: 10.3390/jcm11092551

12. Goldsmith D.R., Haroon E., Miller A.H., Strauss G.P. et al. TNF-α and IL-6 are associated with the deficit syndrome and negative symptoms in patients with chronic schizophrenia. Schizophr. Res. 2018;199:281–4. DOI: 10.1016/j.schres.2018.02.048

13. Goldsmith D.R., Haroon E., Miller A.H., Addington J. et al. Association of baseline inflammatory markers and the development of negative symptoms in individuals at clinical high risk for psychosis. Brain Behav. Immun. 2019;76:268–74. DOI: 10.1016/j.bbi.2018.11.315

14. Momtazmanesh S., Zare-Shahabadi A., Rezaei N. Cytokine alterations in schizophrenia: an updated review. Front. Psychiatry. 2019;10:892. DOI: 10.3389/fpsyt.2019.00892

15. Patlola S.R., Donohoe G., McKernan D.P. The relationship between inflammatory biomarkers and cognitive dysfunction in patients with schizophrenia: a systematic review and meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2023;121:110668. DOI: 10.1016/j.pnpbp.2022.110668

16. Alkan E., Davies G., Evans S.L. Cognitive impairment in schizophrenia: relationships with cortical thickness in fronto-temporal regions, and dissociability from symptom severity. NPJ Schizophr. 2021;7(1):20. DOI: 10.1038/s41537-021-00149-0

17. Ushakov V.L., Malashenkova I.K., Kostyuk G.P., Zakharova N.V. et al. The relationship between inflammation, cognitive disorders and neuroimaging data in schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(11):70–8. (in Russian). DOI: 10.17116/jnevro202012011170

18. Hoseth E.Z., Westlye L.T., Hope S., Dieset I. et al. Association between cytokine levels, verbal memory and hippocampus volume in psychotic disorders and healthy controls. Acta Psychiatr. Scand. 2016;133(1):53–62. DOI: 10.1111/acps.12467

19. Fu G., Zhang W., Dai J., Liu J. et al. Increased peripheral Interleukin 10 relate to white matter integrity in schizophrenia. Front. Neurosci. 2019;13:52. DOI: 10.3389/fnins.2019.00052

20. Moreno C., Parellada M., MacDowell K.S., García-Bueno B. et al.; from the FLAMM-PEPs study, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Differences in the regulation of inflammatory pathways in adolescent- and adult-onset first-episode psychosis. Eur. Child Adolesc. Psychiatry. 2019;28(10):1395–1405. DOI: 10.1007/s00787-019-01295-8

21. Perry B.I., Zammit S., Jones P.B., Khandaker G.M. Childhood inflammatory markers and risks for psychosis and depression at age 24: examination of temporality and specificity of association in a population-based prospective birth cohort. Schizophr. Res. 2021;230:69–76. DOI: 10.1016/j.schres.2021.02.008

22. Mondelli V., Blackman G., Kempton M.J., Pollak T.A. et al.; EU GEI High Risk Study; McGuire P. Serum immune markers and transition to psychosis in individuals at clinical high risk. Brain Behav. Immun. 2023;110:290–6. DOI: 10.1016/j.bbi.2023.03.014

23. Dawidowski B., Górniak A., Podwalski P., Lebiecka Z. et al. The role of cytokines in the pathogenesis of schizophrenia. J. Clin. Med. 2021;10(17):3849. DOI: 10.3390/jcm10173849

24. Lestra V., Romeo B., Martelli C., Benyamina A. et al. Could CRP be a differential biomarker of illness stages in schizophrenia? A systematic review and meta-analysis. Schizophr. Res. 2022;246:175–86. DOI: 10.1016/j.schres.2022.06.026

25. Minaev S.V., Isaeva A.V., Obedin A.N., Bolotov Y.N. et al. C-reactive protein as a key marker of the course of acute inflammatory processes in clinical settings. Medicinskij vestnik Severnogo Kavkaza. 2011;2:95–9. (in Russian). URL: https://cyberleninka.ru/article/n/s-reaktivnyy-belok-glavnyy-marker-dinamiki-techeniyaostryh-vospalitelnyh-protsessov-v-klinicheskih-usloviyah/viewer (дата обращения — 03.06.2023).

26. Sahpolat M., Ayar D., Ari M., Karaman M.A. Elevated monocyte to high-density lipoprotein ratios as an inflammation markers for schizophrenia patients. Clin. Psychopharmacol. Neurosci. 2021;19(1):112–6. DOI: 10.9758/cpn.2021.19.1.112

27. Mednova I.A., Boiko A.S., Kornetova E.G., Semke A.V. et al. Cytokines as potential biomarkers of clinical characteristics of schizophrenia. Life. 2022;12(12):1972. DOI: 10.3390/life12121972

28. Mondelli V., Ciufolini S., Murri M.B., Bonaccorso S. et al. Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis. Schizophr. Bull. 2015;41(5):1162–70. DOI: 10.1093/schbul/sbv028

29. Feng Z., Zhang Y., You X., Zhang W. et al. Effects of risperidone on blood levels of Interleukin-6 in schizophrenia: a meta-analysis. Medicine (Baltimore). 2020;99(15):e19694. DOI: 10.1097/MD.0000000000019694

30. Lee E.E., Ancoli-Israel S., Eyler L.T., Tu X.M. et al. Sleep disturbances and inflammatory biomarkers in schizophrenia: focus on sex differences. Am. J. Geriatr. Psychiatry. 2019;27(1):21–31. DOI: 10.1016/j.jagp.2018.09.017

31. Adamowicz D.H.., Shilling P.D., Palmer B.W., Nguyen T.T. et al. Associations between inflammatory marker profiles and neurocognitive functioning in people with schizophrenia and nonpsychiatric comparison subjects. J. Psychiatr. Res. 2022;149:106– 13. DOI: 10.1016/j.jpsychires.2022.02.029

32. Zhu X., Zhou J., Zhu Y., Yan F. et al. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas. Psychiatry. 2022;30(1):95–9. DOI: 10.1177/10398562211022753

33. Räuber S., Heming M., Repple J., Ruland T. et al. Cerebrospinal fluid flow cytometry distinguishes psychosis spectrum disorders from differential diagnoses. Mol. Psychiatry. 2021;26(12):7661–70. DOI: 10.1038/s41380-021-01244-5

34. Balcioglu Y.H., Kirlioglu S.S. C-reactive protein/albumin and neutrophil/albumin ratios as novel inflammatory markers in patients with schizophrenia. Psychiatry Investig. 2020;17(9):902–10. DOI: 10.30773/pi.2020.0185

35. Kılıç N., Tasci G., Yılmaz S., Öner P. et al. Monocyte/HDL cholesterol ratios as a new inflammatory marker in patients with schizophrenia. J. Pers. Med. 2023;13(2):276. DOI: 10.3390/jpm13020276

36. Brusov O.S., Matveev И.A., Kirillov P.S., Factor M.I. et al. Risk assessment of thrombotic events in patients with schizophrenia and schizoaffective disorder in the acute state: the "fibrinodynamics" technology. S.S. Korsakov Journal of Neurology and Psychiatry. 2017;117(11):91–100. (in Russian). DOI: 10.17116/jnevro201711711191-100

37. Endres D., von Zedtwitz K., Matteit I., Bünger I. et al. Spectrum of novel anti-central nervous system autoantibodies in the cerebrospinal fluid of 119 patients with schizophreniform and affective disorders. Biol. Psychiatry. 2022;92(4):261–74. DOI: 10.1016/j.biopsych.2022.02.010

38. Bishop J.R., Zhang L., Lizano P. Inflammation subtypes and translating inflammation-related genetic findings in schizophrenia and related psychoses: a perspective on pathways for treatment stratification and novel therapies. Harv. Rev. Psychiatry. 2022;30(1):59–70. DOI: 10.1097/HRP.0000000000000321

39. Sæther L.S., Ueland T., Haatveit B., Maglanoc L.A. et al. Inflammation and cognition in severe mental illness: patterns of covariation and subgroups. Mol. Psychiatry. 2023;28(3):1284–92. DOI: 10.1038/s41380-022-01924-w

40. Miller B.J., Goldsmith D.R. Evaluating the hypothesis that schizophrenia is an inflammatory disorder. Focus (Am. Psychiatr. Publ.). 2020;18(4):391–401. DOI: 10.1176/appi.focus.20200015

41. Shivakumar V., Debnath M., Venugopal D., Rajasekaran A. et al. Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia. Cytokine. 2018;107:59–64. DOI: 10.1016/j.cyto.2017.11.016

42. Golimbet V.E., Klyushnik T.P. Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(10):66– 71. (in Russian). DOI: 10.17116/jnevro202212210166

43. Klyushnik T.P., Zozulya S.A., Androsova L.V., Sarmanova Z.V. et al. Immunological monitoring of endogenous attack-like psychoses. S.S. Korsakov Journal of Neurology and Psychiatry. 2014;114(2):37–41. (in Russian). URL: https://www. mediasphera.ru/issues/zhurnal-nevrologii-i-psikhiatrii-im-s-skorsakova/2014/2/downloads/ru/031997-7298201427 (дата обращения — 04.06.2023).

44. Klyushnik T.P., Zozulya S.A., Oleichik I.V. Novosibirsk. Markers of immune system activation in monitoring of the course of endogenous mental disorders. In: Bokhan N.A., Ivanova S.A. (ed.). Biological markers of schizophrenia: search and clinical application. Novosibirsk: Publishing House of the Siberian branch of the Russian Academy of Sciences. Izd-vo SO RAN; 2017: 34–46. (in Russian).

45. Paramonova N.S., Karchevskij A.A., SHulika V.R. Diagnosis and forecasting of the course of destructive ulcerative lesions on the gastric and duodenal mucosa on the basis of the proteolytically antiproteolytic serum system in children with connective tissue dysplasia. Zhurnal Grodnenskogo gosudarstvennogo medicinskogo universiteta. 2017;2:210–5. (in Russian). URL: https://cyberleninka.ru/article/n/diagnostikai-prognozirovanie-techeniya-destruktivno-yazvennyh-porazheniyslizistoy-obolochki-zheludka-i-dvenadtsatiperstnoy-kishki/viewer (дата обращения — 04.06.2023).

46. Santos-Lima B., Pietronigro E.C., Terrabuio E., Zenaro E. et al. The role of neutrophils in the dysfunction of central nervous system barriers. Front. Aging Neurosci. 2022;14:965169. DOI: 10.3389/fnagi.2022.965169

47. Sarmanova Z.V., Zozulya S.A., Otman I.N., Prokhorova T.A. et al. Relationship between biomarkers of inflammation, subpopulation composition of monocytes and activity of platelet enzymes in patients with schizophrenia. Pathogenesis. 2022;20(3):121–2. (in Russian). DOI: 10.25557/2310-0435.2022.03.121-122

48. Klyushnik T.P., Smulevich A.B., Zozulya S.A., Borisova P.O. et al. Catatonia: immunological aspect (on the model of motor symptom complexes in the clinic of schizophrenia and schizophrenic spectrum disorders). Psychiatry. 2022;20(1):17–25. (in Russian). DOI: 10.30629/2618-6667-2022-20-1-17-25

49. Klyushnik T.P., Smulevich A.B., Zozulya S.A., Romanov D.V. et al. Clinical and immunological aspects of delusional disorders in paranoid schizophrenia. Delusional disorders in paranoid schizophrenia (immunological aspects). Psychiatry. 2023;21(2):6– 16. (in Russian). DOI: 10.30629/2618-6667-2023-21-2-6-16

50. Yakimets A.V., Zozulya S.A., Oleĭchik I.V., Klyushnik T.P. Dynamics of clinical and biological indices of the asthenic symptom-complex during immunotropic therapy of patients with schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(3):70–6. (in Russian). DOI: 10.17116/jnevro20181183170-76

51. Klyushnik T.P., Androsova L.V., Simashkova N.V., Zozulya S.A. et al. Innate and adaptive immunity in children with psychotic forms of autism-spectrum disorders. S.S. Korsakov Journal of Neurology and Psychiatry. 2011;111(8):41–5. (in Russian). URL: https://www.mediasphera.ru/issues/zhurnal-nevrologiii-psikhiatrii-im-s-s-korsakova/2011/8/downloads/ru/031997-7298201189 (дата обращения — 12.07.2023).

52. Yao H.W., Kuan C.Y. Early neutrophil infiltration is critical for inflammation-sensitized hypoxic-ischemic brain injury in newborns. J. Cereb. Blood Flow Metab. 2020;40(11):2188–200. DOI: 10.1177/0271678X19891839

53. Prinz M., Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat. Neurosci. 2017;20(2):136–44. DOI: 10.1038/nn.4475


Review

For citations:


Zozulya S.A., Sarmanova Z.V., Otman I.N., Klyushnik T.P. Inflammatory Markers in Schizophrenia Patients: Scientific and Practical Significance. Title. 2023;22(6):7-14. (In Russ.) https://doi.org/10.31550/1727-2378-2023-22-6-7-14

Views: 11


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1727-2378 (Print)
ISSN 2713-2994 (Online)