The Correlation of Blood Immune Cells with the Pathogenesis of Schizophrenia: A Meta-Analysis
,
Abstract
Background: We have included literature on changes in immune cells in patients with schizophrenia and have systematically and quantitatively reviewed these studies through meta-analysis, with a view to understanding the potential effects of immune system dysfunction on the pathophysiology of schizophrenia.
Methods: We conducted a systematic search in PubMed, Embase, Web of Science, and the Cochrane Library, covering publications from inception to Sep 25, 2023. The systematic review followed the PRISMA guidelines, and a random-effects meta-analysis was performed. Heterogeneity was evaluated using the I² index, and sensitivity analyses were conducted to assess the stability of the findings.
Results: The systematic review includes 42 studies on schizophrenia. Meta-analysis revealed that compared to the control group, schizophrenia patients had significantly higher white blood cell counts (WBC, P<0.01), CD4 absolute values (P=0.02), CD4 percentage (CD4%, P=0.05), CD4/CD8 ratio (P<0.01), monocyte-to-lymphocyte ratio (MLR, P<0.01), neutrophil-to-lymphocyte ratio (NLR, P<0.01), and platelet-to-lymphocyte ratio (PLR, P<0.01). No significant differences were observed for other immune markers in the meta-analysis.
Conclusion: The number of immune cells in the blood of patients with schizophrenia increased. Therefore, more research on immune system abnormalities in schizophrenia patients is needed to better understand the underlying mechanisms between schizophrenia and immune cell parameters.
1. Saha S, Chant D, Welham J, McGrath J (2005). A systematic review of the prevalence of schizophrenia. PLoS Med, 2 (5):e141.
2. Charlson FJ, Ferrari AJ, Santomauro DF, et al (2018). Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull, 44 (6):1195-1203.
3. McGrath J, Saha S, Chant D, et al (2008). Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev, 30:67-76.
4. Cloutier M, Aigbogun MS, Guerin A, et al (2016). The Economic Burden of Schizophrenia in the United States in 2013. J Clin Psychiatry, 77 (6):764-71.
5. Winship IR, Dursun SM, Baker GB, et al (2019). An Overview of Animal Models Related to Schizophrenia. Can J Psychiatry, 64 (1):5-17.
6. Häfner H, an der Heiden W (1997). Epidemiology of schizophrenia. Can J Psychiatry, 42 (2):139-51.
7. Miller BJ, Goldsmith DR (2017). Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions. Neuropsychopharmacology, 42 (1):299-317.
8. Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511 (7510):421-7.
9. Duan L, Li S, Chen D, et al (2024). Causality between autoimmune diseases and schizophrenia: a bidirectional Mendelian randomization study. BMC Psychiatry, 24 (1):817.
10. Müller N (2018). Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations. Schizophr Bull, 44 (5):973-982.
11. Kulaga SS, Miller CWT (2021). Viral respiratory infections and psychosis: A review of the literature and the implications of COVID-19. Neurosci Biobehav Rev, 127:520-530.
12. Kirkpatrick B, Miller BJ (2013). Inflammation and schizophrenia. Schizophr Bull, 39 (6):1174-9.
13. Bustan Y, Drapisz A, Ben Dor DH, et al (2018). Elevated neutrophil to lymphocyte ratio in non-affective psychotic adolescent inpatients: Evidence for early association between inflammation and psychosis. Psychiatry Res, 262:149-153.
14. Chang SH, Chiang SY, Chiu CC, et al (2011). Expression of anti-cardiolipin antibodies and inflammatory associated factors in patients with schizophrenia. Psychiatry Res, 187 (3):341-6.
15. Liberati A, Altman DG, Tetzlaff J, Mulrow C, et al (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol, 62(10):e1-34.
16. Wiebe N, Vandermeer B, Platt RW, et al (2006). A systematic review identifies a lack of standardization in methods for handling missing variance data. J Clin Epidemiol, 59 (4):342-53.
17. Higgins JP, Spiegelhalter DJ (2002). Being sceptical about meta-analyses: a Bayesian perspective on magnesium trials in myocardial infarction. Int J Epidemiol, 31 (1):96-104.
18. Hardy RJ, Thompson SG (1998). Detecting and describing heterogeneity in meta-analysis. Stat Med, 17 (8):841-56.
19. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50 (4):1088-101.
20. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315 (7109):629-34.
21. Özdin S, Sarisoy G, Böke Ö (2017). 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, 71 (7):509-512.
22. Steiner J, Jacobs R, Panteli B, et al (2010). Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. Eur Arch Psychiatry Clin Neurosci, 260 (7):509-18.
23. Achiron A, Noy S, Pras E, et al (1994). T-cell subsets in acute psychotic schizophrenic patients. Biol Psychiatry, 35 (1):27-31.
24. Baskak SC, Ozsan H, Baskak B, et al (2008). [Peripheral blood T-lymphocyte and T-lymphocyte subset ratios before and after treatment in schizophrenia patients not taking antipsychotic medication]. Turk Psikiyatri Derg, 19 (1):5-12.
25. Carlton E, Falcone T, Batra A, et al (2009). Do Systemic Inflammation and Blood-Brain Barrier Failure Play a Role in Pediatric Psychosis? Cleveland Clinic Journal of Medicine, 76(Supplement 2), S93a.
26. Ganguli R, Rabin BS (1993). CD5 positive B lymphocytes in schizophrenia: no alteration in numbers or percentage as compared with control subjects. Psychiatry Res, 48 (1):69-78.
27. Henneberg A, Riedl B, Dumke HO, et al (1990). T-lymphocyte subpopulations in schizophrenic patients. Eur Arch Psychiatry Neurol Sci, 239 (5):283-4.
28. Maino K, Gruber R, Riedel M, et al (2007). T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment. Psychiatry Res, 152 (2-3):173-80.
29. Masserini C, Vita A, Basile R, et al (1990). Lymphocyte subsets in schizophrenic disorders. Relationship with clinical, neuromorphological and treatment variables. Schizophr Res, 3 (4):269-75.
30. Müller N, Ackenheil M, Hofschuster E, et al (1991). Cellular immunity in schizophrenic patients before and during neuroleptic treatment. Psychiatry Res, 37 (2):147-60.
31. Nyland H, Naess A, Lunde H (1980). Lymphocyte subpopulations in peripheral blood from schizophrenic patients. Acta Psychiatr Scand, 61 (4):313-8.
32. Rudolf S, Schlenke P, Broocks A, et al (2004). Search for atypical lymphocytes in schizophrenia. World J Biol Psychiatry, 5 (1):33-7.
33. Sasaki T, Nanko S, Fukuda R, et al (1994). Changes of immunological functions after acute exacerbation in schizophrenia. Biol Psychiatry, 35 (3):173-8.
34. Sperner-Unterweger B, Whitworth A, Kemmler G, et al (1999). T-cell subsets in schizophrenia: a comparison between drug-naive first episode patients and chronic schizophrenic patients. Schizophr Res, 38 (1):61-70.
35. Theodoropoulou S, Spanakos G, Baxevanis CN, et al (2001). Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients. Schizophr Res, 47 (1):13-25.
36. Orhan F, Schwieler L, Fatouros-Bergman H, et al (2018). Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis. Acta Psychiatr Scand, 138 (5):432-440.
37. Kulaksizoglu B, Kulaksizoglu S (2016). Relationship between neutrophil/lymphocyte ratio with oxidative stress and psychopathology in patients with schizophrenia. Neuropsychiatr Dis Treat, 12:1999-2005.
38. Núñez C, Stephan-Otto C, Usall J, et al(2019). Neutrophil Count Is Associated With Reduced Gray Matter and Enlarged Ventricles in First-Episode Psychosis. Schizophr Bull, 45 (4):846-858.
39. Printz DJ, Strauss DH, Goetz R, et al (1999). Elevation of CD5+ B lymphocytes in schizophrenia. Biol Psychiatry, 46 (1):110-8.
40. Schleifer SJ, Keller SE, Siris SG, et al(1985). Depression and immunity. Lymphocyte function in ambulatory depressed patients, hospitalized schizophrenic patients, and patients hospitalized for herniorrhaphy. Arch Gen Psychiatry, 42 (2):129-33.
41. Kelly DL, Li X, Kilday C, et al (2018). Increased circulating regulatory T cells in medicated people with schizophrenia. Psychiatry Res, 269:517-523.
42. Semiz M, Yildirim O, Canan F, et al (2014). Elevated neutrophil/lymphocyte ratio in patients with schizophrenia. Psychiatr Danub, 26 (3):220-5.
43. Garcia-Rizo C, Casanovas M, Fernandez-Egea E, et al (2019). Blood cell count in antipsychotic-naive patients with non-affective psychosis. Early Interv Psychiatry, 13 (1):95-100.
44. Moody G, Miller BJ (2018). Total and differential white blood cell counts and hemodynamic parameters in first-episode psychosis. Psychiatry Res, 260:307-312.
45. Yüksel RN, Ertek IE, Dikmen AU, et al (2018). High neutrophil-lymphocyte ratio in schizophrenia independent of infectious and metabolic parameters. Nord J Psychiatry, 72 (5):336-340.
46. Miller BJ, Kandhal P, Rapaport MH, et al (2015). Total and differential white blood cell counts, high-sensitivity C-reactive protein, and cardiovascular risk in non-affective psychoses. Brain Behav Immun, 45:28-35.
47. Pavlović M, Babić D, Rastović P, et al (2016). Metabolic Syndrome, Total and Differential White Blood Cell Counts in Patients with Schizophrenia. Psychiatr Danub, 2:216-222.
48. Yu Q, Weng W, Zhou H, et al (2020). Elevated Platelet Parameter in First-Episode Schizophrenia Patients: A Cross-Sectional Study. J Interferon Cytokine Res, 40 (11):524-529.
49. Rabin BS, Ganguli R, Cunnick JE, et al (1988). The central nervous system--immune system relationship. Clin Lab Med, 8 (2):253-68.
50. Wilke I, Arolt V, Rothermundt M, et al (1996). Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci, 246 (5):279-84.
51. Balcioglu YH, Kirlioglu SS (2020). C-Reactive Protein/Albumin and Neutrophil/Albumin Ratios as Novel Inflammatory Markers in Patients with Schizophrenia. Psychiatry Investig, 17 (9):902-910.
52. Kronfol Z, House JD (1988). Immune function in mania. Biol Psychiatry, 24 (3):341-3.
53. Bulut NS, Yorguner N, Çarkaxhiu Bulut G (2021). The severity of inflammation in major neuropsychiatric disorders: comparison of neutrophil-lymphocyte and platelet-lymphocyte ratios between schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and obsessive compulsive disorder. Nord J Psychiatry, 75 (8):624-632.
54. Inaltekin A, Yağci İ (2023). Evaluation of Simple Markers of Inflammation and Systemic Immune Inflammation Index in Schizophrenia, Bipolar Disorder Patients and Healthy Controls. Turk Psikiyatri Derg, 34 (1):11-15.
55. Kılıç N, Tasci G, Yılmaz S, et al (2023). Monocyte/HDL Cholesterol Ratios as a New Inflammatory Marker in Patients with Schizophrenia. J Pers Med, 13 (2):276.
56. Sahbaz C, Zibandey N, Kurtulmus A, et al (2020). Reduced regulatory T cells with increased proinflammatory response in patients with schizophrenia. Psychopharmacology (Berl), 237 (6):1861-1871.
57. Sahpolat M, Karaman MA, Copur EO, et al (2022). Increased Neutrophil to Lymphocyte and Platelet of Lymphocyte Ratios in Patients with First Episode Psychosis. Medical Journal of Bakirkoy, 18 (1):59-64.
58. Wei Y, Wang T, Li G, et al (2022). Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder. Front Psychiatry, 13:941728.
59. Xu H, Wei Y, Zheng L, et al (2022). Relation Between Unconjugated Bilirubin and Peripheral Biomarkers of Inflammation Derived From Complete Blood Counts in Patients With Acute Stage of Schizophrenia. Front Psychiatry, 13:843985.
60. Zhu X, Zhou J, Zhu Y, et al (2022). Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas Psychiatry, 30 (1):95-99.
61. Sekar A, Bialas AR, de Rivera H, Davis A, et al (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530 (7589):177-83.
62. Jackson AJ, Miller BJ (2020). Meta-analysis of total and differential white blood cell counts in schizophrenia. Acta Psychiatr Scand, 142 (1):18-26.
63. Al-Diwani AAJ, Pollak TA, Irani SR, et al (2017). Psychosis: an autoimmune disease? Immunology, 152 (3):388-401.
64. Li Y, Ong JWX, See YM, et al (2025). Immunophenotyping schizophrenia subtypes stratified by antipsychotic response. Brain Behav Immun, 123:656-671.
65. Huang K, Tang Y, Chen Z, et al (2022). Comparison of Hematological Parameters Between First-Episode Schizophrenia and Anti-NMDAR Encephalitis. Front Cell Dev Biol, 10:895178.
66. Özdin S, Böke Ö (2019). Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in different stages of schizophrenia. Psychiatry Res, 271:131-135.
67. Šagud M, Madžarac Z, Nedic Erjavec G, et al (2023). The Associations of Neutrophil-Lymphocyte, Platelet-Lymphocyte, Monocyte-Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia. Biomolecules, 13 (2):297.
2. Charlson FJ, Ferrari AJ, Santomauro DF, et al (2018). Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull, 44 (6):1195-1203.
3. McGrath J, Saha S, Chant D, et al (2008). Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev, 30:67-76.
4. Cloutier M, Aigbogun MS, Guerin A, et al (2016). The Economic Burden of Schizophrenia in the United States in 2013. J Clin Psychiatry, 77 (6):764-71.
5. Winship IR, Dursun SM, Baker GB, et al (2019). An Overview of Animal Models Related to Schizophrenia. Can J Psychiatry, 64 (1):5-17.
6. Häfner H, an der Heiden W (1997). Epidemiology of schizophrenia. Can J Psychiatry, 42 (2):139-51.
7. Miller BJ, Goldsmith DR (2017). Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions. Neuropsychopharmacology, 42 (1):299-317.
8. Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511 (7510):421-7.
9. Duan L, Li S, Chen D, et al (2024). Causality between autoimmune diseases and schizophrenia: a bidirectional Mendelian randomization study. BMC Psychiatry, 24 (1):817.
10. Müller N (2018). Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations. Schizophr Bull, 44 (5):973-982.
11. Kulaga SS, Miller CWT (2021). Viral respiratory infections and psychosis: A review of the literature and the implications of COVID-19. Neurosci Biobehav Rev, 127:520-530.
12. Kirkpatrick B, Miller BJ (2013). Inflammation and schizophrenia. Schizophr Bull, 39 (6):1174-9.
13. Bustan Y, Drapisz A, Ben Dor DH, et al (2018). Elevated neutrophil to lymphocyte ratio in non-affective psychotic adolescent inpatients: Evidence for early association between inflammation and psychosis. Psychiatry Res, 262:149-153.
14. Chang SH, Chiang SY, Chiu CC, et al (2011). Expression of anti-cardiolipin antibodies and inflammatory associated factors in patients with schizophrenia. Psychiatry Res, 187 (3):341-6.
15. Liberati A, Altman DG, Tetzlaff J, Mulrow C, et al (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol, 62(10):e1-34.
16. Wiebe N, Vandermeer B, Platt RW, et al (2006). A systematic review identifies a lack of standardization in methods for handling missing variance data. J Clin Epidemiol, 59 (4):342-53.
17. Higgins JP, Spiegelhalter DJ (2002). Being sceptical about meta-analyses: a Bayesian perspective on magnesium trials in myocardial infarction. Int J Epidemiol, 31 (1):96-104.
18. Hardy RJ, Thompson SG (1998). Detecting and describing heterogeneity in meta-analysis. Stat Med, 17 (8):841-56.
19. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50 (4):1088-101.
20. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315 (7109):629-34.
21. Özdin S, Sarisoy G, Böke Ö (2017). 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, 71 (7):509-512.
22. Steiner J, Jacobs R, Panteli B, et al (2010). Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. Eur Arch Psychiatry Clin Neurosci, 260 (7):509-18.
23. Achiron A, Noy S, Pras E, et al (1994). T-cell subsets in acute psychotic schizophrenic patients. Biol Psychiatry, 35 (1):27-31.
24. Baskak SC, Ozsan H, Baskak B, et al (2008). [Peripheral blood T-lymphocyte and T-lymphocyte subset ratios before and after treatment in schizophrenia patients not taking antipsychotic medication]. Turk Psikiyatri Derg, 19 (1):5-12.
25. Carlton E, Falcone T, Batra A, et al (2009). Do Systemic Inflammation and Blood-Brain Barrier Failure Play a Role in Pediatric Psychosis? Cleveland Clinic Journal of Medicine, 76(Supplement 2), S93a.
26. Ganguli R, Rabin BS (1993). CD5 positive B lymphocytes in schizophrenia: no alteration in numbers or percentage as compared with control subjects. Psychiatry Res, 48 (1):69-78.
27. Henneberg A, Riedl B, Dumke HO, et al (1990). T-lymphocyte subpopulations in schizophrenic patients. Eur Arch Psychiatry Neurol Sci, 239 (5):283-4.
28. Maino K, Gruber R, Riedel M, et al (2007). T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment. Psychiatry Res, 152 (2-3):173-80.
29. Masserini C, Vita A, Basile R, et al (1990). Lymphocyte subsets in schizophrenic disorders. Relationship with clinical, neuromorphological and treatment variables. Schizophr Res, 3 (4):269-75.
30. Müller N, Ackenheil M, Hofschuster E, et al (1991). Cellular immunity in schizophrenic patients before and during neuroleptic treatment. Psychiatry Res, 37 (2):147-60.
31. Nyland H, Naess A, Lunde H (1980). Lymphocyte subpopulations in peripheral blood from schizophrenic patients. Acta Psychiatr Scand, 61 (4):313-8.
32. Rudolf S, Schlenke P, Broocks A, et al (2004). Search for atypical lymphocytes in schizophrenia. World J Biol Psychiatry, 5 (1):33-7.
33. Sasaki T, Nanko S, Fukuda R, et al (1994). Changes of immunological functions after acute exacerbation in schizophrenia. Biol Psychiatry, 35 (3):173-8.
34. Sperner-Unterweger B, Whitworth A, Kemmler G, et al (1999). T-cell subsets in schizophrenia: a comparison between drug-naive first episode patients and chronic schizophrenic patients. Schizophr Res, 38 (1):61-70.
35. Theodoropoulou S, Spanakos G, Baxevanis CN, et al (2001). Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients. Schizophr Res, 47 (1):13-25.
36. Orhan F, Schwieler L, Fatouros-Bergman H, et al (2018). Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis. Acta Psychiatr Scand, 138 (5):432-440.
37. Kulaksizoglu B, Kulaksizoglu S (2016). Relationship between neutrophil/lymphocyte ratio with oxidative stress and psychopathology in patients with schizophrenia. Neuropsychiatr Dis Treat, 12:1999-2005.
38. Núñez C, Stephan-Otto C, Usall J, et al(2019). Neutrophil Count Is Associated With Reduced Gray Matter and Enlarged Ventricles in First-Episode Psychosis. Schizophr Bull, 45 (4):846-858.
39. Printz DJ, Strauss DH, Goetz R, et al (1999). Elevation of CD5+ B lymphocytes in schizophrenia. Biol Psychiatry, 46 (1):110-8.
40. Schleifer SJ, Keller SE, Siris SG, et al(1985). Depression and immunity. Lymphocyte function in ambulatory depressed patients, hospitalized schizophrenic patients, and patients hospitalized for herniorrhaphy. Arch Gen Psychiatry, 42 (2):129-33.
41. Kelly DL, Li X, Kilday C, et al (2018). Increased circulating regulatory T cells in medicated people with schizophrenia. Psychiatry Res, 269:517-523.
42. Semiz M, Yildirim O, Canan F, et al (2014). Elevated neutrophil/lymphocyte ratio in patients with schizophrenia. Psychiatr Danub, 26 (3):220-5.
43. Garcia-Rizo C, Casanovas M, Fernandez-Egea E, et al (2019). Blood cell count in antipsychotic-naive patients with non-affective psychosis. Early Interv Psychiatry, 13 (1):95-100.
44. Moody G, Miller BJ (2018). Total and differential white blood cell counts and hemodynamic parameters in first-episode psychosis. Psychiatry Res, 260:307-312.
45. Yüksel RN, Ertek IE, Dikmen AU, et al (2018). High neutrophil-lymphocyte ratio in schizophrenia independent of infectious and metabolic parameters. Nord J Psychiatry, 72 (5):336-340.
46. Miller BJ, Kandhal P, Rapaport MH, et al (2015). Total and differential white blood cell counts, high-sensitivity C-reactive protein, and cardiovascular risk in non-affective psychoses. Brain Behav Immun, 45:28-35.
47. Pavlović M, Babić D, Rastović P, et al (2016). Metabolic Syndrome, Total and Differential White Blood Cell Counts in Patients with Schizophrenia. Psychiatr Danub, 2:216-222.
48. Yu Q, Weng W, Zhou H, et al (2020). Elevated Platelet Parameter in First-Episode Schizophrenia Patients: A Cross-Sectional Study. J Interferon Cytokine Res, 40 (11):524-529.
49. Rabin BS, Ganguli R, Cunnick JE, et al (1988). The central nervous system--immune system relationship. Clin Lab Med, 8 (2):253-68.
50. Wilke I, Arolt V, Rothermundt M, et al (1996). Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci, 246 (5):279-84.
51. Balcioglu YH, Kirlioglu SS (2020). C-Reactive Protein/Albumin and Neutrophil/Albumin Ratios as Novel Inflammatory Markers in Patients with Schizophrenia. Psychiatry Investig, 17 (9):902-910.
52. Kronfol Z, House JD (1988). Immune function in mania. Biol Psychiatry, 24 (3):341-3.
53. Bulut NS, Yorguner N, Çarkaxhiu Bulut G (2021). The severity of inflammation in major neuropsychiatric disorders: comparison of neutrophil-lymphocyte and platelet-lymphocyte ratios between schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and obsessive compulsive disorder. Nord J Psychiatry, 75 (8):624-632.
54. Inaltekin A, Yağci İ (2023). Evaluation of Simple Markers of Inflammation and Systemic Immune Inflammation Index in Schizophrenia, Bipolar Disorder Patients and Healthy Controls. Turk Psikiyatri Derg, 34 (1):11-15.
55. Kılıç N, Tasci G, Yılmaz S, et al (2023). Monocyte/HDL Cholesterol Ratios as a New Inflammatory Marker in Patients with Schizophrenia. J Pers Med, 13 (2):276.
56. Sahbaz C, Zibandey N, Kurtulmus A, et al (2020). Reduced regulatory T cells with increased proinflammatory response in patients with schizophrenia. Psychopharmacology (Berl), 237 (6):1861-1871.
57. Sahpolat M, Karaman MA, Copur EO, et al (2022). Increased Neutrophil to Lymphocyte and Platelet of Lymphocyte Ratios in Patients with First Episode Psychosis. Medical Journal of Bakirkoy, 18 (1):59-64.
58. Wei Y, Wang T, Li G, et al (2022). Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder. Front Psychiatry, 13:941728.
59. Xu H, Wei Y, Zheng L, et al (2022). Relation Between Unconjugated Bilirubin and Peripheral Biomarkers of Inflammation Derived From Complete Blood Counts in Patients With Acute Stage of Schizophrenia. Front Psychiatry, 13:843985.
60. Zhu X, Zhou J, Zhu Y, et al (2022). Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas Psychiatry, 30 (1):95-99.
61. Sekar A, Bialas AR, de Rivera H, Davis A, et al (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530 (7589):177-83.
62. Jackson AJ, Miller BJ (2020). Meta-analysis of total and differential white blood cell counts in schizophrenia. Acta Psychiatr Scand, 142 (1):18-26.
63. Al-Diwani AAJ, Pollak TA, Irani SR, et al (2017). Psychosis: an autoimmune disease? Immunology, 152 (3):388-401.
64. Li Y, Ong JWX, See YM, et al (2025). Immunophenotyping schizophrenia subtypes stratified by antipsychotic response. Brain Behav Immun, 123:656-671.
65. Huang K, Tang Y, Chen Z, et al (2022). Comparison of Hematological Parameters Between First-Episode Schizophrenia and Anti-NMDAR Encephalitis. Front Cell Dev Biol, 10:895178.
66. Özdin S, Böke Ö (2019). Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in different stages of schizophrenia. Psychiatry Res, 271:131-135.
67. Šagud M, Madžarac Z, Nedic Erjavec G, et al (2023). The Associations of Neutrophil-Lymphocyte, Platelet-Lymphocyte, Monocyte-Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia. Biomolecules, 13 (2):297.
| Files | ||
| Issue | Vol 54 No 8 (2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v54i8.19566 | |
| Keywords | ||
| Schizophrenia White blood cells Meta-analysis Immune cells Systematic review | ||
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How to Cite
1.
Xue F, Li Z, Yan L, YU Q, Zhang Y. The Correlation of Blood Immune Cells with the Pathogenesis of Schizophrenia: A Meta-Analysis. Iran J Public Health. 2025;54(8):1563-1576.
