Longitudinal Assessment of Alterations in Peripheral Inflammatory Markers Over a Hospitalization Period in Patients with Schizophrenia
Abstract
Objective: To assess the effects of regular medication administration, diet, sleep, and physical activity provided by hospital care on inflammatory markers in schizophrenia patients. The primary hypothesis of our study is that the assembly of various factors, will reduce low-grade inflammation in a short period.
Materials and Methods: This retrospective longitudinal study involved 106 patients diagnosed with schizophrenia who met the exclusion and inclusion criteria. Inflammatory markers such as neutrophil-to-lymphocyte Ratios (NLR), monocyte-to-lymphocyte ratios (MLR), platelet-to-lymphocyte ratios (PLR), C-reactive protein-to-albumin ratios (CAR), and systemic immune inflammation indices (SII) were calculated at the time of hospital admission and after three weeks.
Results: The mean age of the participants was 39.0±13.1 years and the majority were male (n: 75). Reductions were observed in all inflammatory markers after three weeks. The CRP decreased from a median value of 2.6 (interquartile range (IQR): 1.1-5.3) to 1.90 (IQR: 0.85-3.30) (p=0.001, effect size=0.375). The CAR changed from 0.064 (IQR: 0.026-0.115) to 0.043 (IQR: 0.017-0.077) (p=0.005, effect size=0.371). The NLR demonstrated a significant reduction from 2.31 (IQR: 1.73-3.24) to 1.73 (IQR: 1.28-2.27) (p<0.001, effect size=0.647). The SII decreased from 634 (IQR: 425-870) to 470 (IQR: 321-645) (p<0.001, effect size=0.577). The PLR went down from 9.85 (IQR: 7.4-12.7) to 8.21 (IQR: 6.22-10.3) (p<0.001, effect size=0.547). Lastly, the MLR reduced from 0.297 (IQR: 0.221-0.378) to 0.258 (IQR: 0.195-0.319) (p<0.001, effect size=0.522).
Conclusion: This study underscores the influence of regular antipsychotic treatment and hospital care in reducing inflammation markers like NLR, MLR, PLR, SII, and CAR in schizophrenia patients. Future studies should explore the potential of markers like CAR and SII in detecting low-grade inflammation, and further probe into the role of sleep, nutrition, and physical activity, emphasising the paramount role of comprehensive hospital care.
Keywords
schizophrenia low-grade inflammation antipsychotics systemic immune inflamattion index (SII) C-reaktive protein (CRP)- to-albumin ratio (CAR)
References
- Soygür H. The concept of schizophrenia: ‘’Shall we destroy and rebuild, repair and update?’’ Update in Psychiatry, 2023; 13(1):1-9.
- Ermakov EA, Melamud MM, Buneva VN, Ivanova SA. Immune system abnormalities in schizophrenia: An integrative view and translational perspectives. Front Psychiatry, 2022; 25(13):880568.
- Zhu X, Zhou J, Zhu Y, Yan F, Han X, Tan Y, Li R. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas Psychiatry, 2022; 30(1):95-99.
- Tsai SJ. Role of interleukin 8 in depression and other psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry, 2021; 106:110173.
- 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.
- Jarskog LF, Xiao H, Wilkie MB, Lauder JM, Gilmore JH. Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro. Int J Dev Neurosci. 1997 Oct;15(6):711-716.
- Rodrigues-Amorim D, Rivera-Baltanás T, Spuch C, Caruncho HJ, González-Fernandez Á, Olivares JM, et al. Cytokines dysregulation in schizophrenia: A systematic review of psychoneuroimmune relationship. Schizophr Res, 2018; 197:19-33.
- Bulut NS, Yorguner N, Çarkaxhiu Bulut G. 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, 2021; 75(8):624-632.
- Inanli I, Aydin M, Çaliskan AM, Eren I. Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder. Nord J Psychiatry. 2019;73(6):372-379.
- Huang K, Tang Y, Chen Z, Ding S, Zeng H, Zhao Y, Yu Q, Liu Y. Comparison of hematological parameters between first-episode schizophrenia and anti-NMDAR encephalitis. Front Cell Dev Biol, 2022; 10:895178.
- Mazza MG, Lucchi S, Rossetti A, Clerici M. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in non-affective psychosis: A meta-analysis and systematic review. World J Biol Psychiatry, 2020; 21(5):326-338.
- Šagud M, Madžarac Z, Nedic Erjavec G, Šimunović Filipčić I, Mikulić FL, Rogić D, et al. The associations of neutrophil-lymphocyte, platelet-lymphocyte, monocyte-lymphocyte ratios and immune-inflammation index with negative symptoms in patients with schizophrenia. Biomolecules, 2023; 13(2):297.
- Inaltekin A, Yağci İ. Evaluation of simple markers of inflammation and systemic immune inflammation index in schizophrenia, bipolar disorder patients and healthy controls. Turk Psikiyatri Derg, 2023; 34(1):11-15.
- Ranzani OT, Zampieri FG, Forte DN, Azevedo LC, Park M. C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One. 2013;8(3):e59321.
- Balcioglu YH, Kirlioglu SS. C-Reactive Protein/Albumin and Neutrophil/Albumin Ratios as Novel Inflammatory Markers in Patients with Schizophrenia. Psychiatry Investig, 2020; 17(9):902-910.
- Balcioglu YH, Balcioglu SSK, Oncu F, Turkcan A, Yorulmaz AC. Impulsive and aggressive traits and increased peripheral inflammatory status as psychobiological substrates of homicide behavior in schizophrenia. The European Journal of Psychiatry, 2022; 36(3), 207-214.
- Karageorgiou V, Milas GP, Michopoulos I. Neutrophil-to-lymphocyte ratio in schizophrenia: A systematic review and meta-analysis. Schizophr Res, 2019; 206:4-12.
- American Psychiatric Association: Desk Reference to the Diagnostic Criteria From DSM-5. Arlington, VA, American Psychiatric Association, 2013.
- Sisman AR, Kume T, Akan P, Tuncel P. C-reactive protein: Clinical significance, improvements in methodology, pre-analytical and analytical variations. Türk Klinik Biyokimya Derg, 2007; 5(1): 33-41.
- Zhou X, Wang X, Li R, Yan J, Xiao Y, Li W, et al. Neutrophil-to-Lymphocyte Ratio Is Independently Associated With Severe Psychopathology in Schizophrenia and Is Changed by Antipsychotic Administration: A Large-Scale Cross-Sectional Retrospective Study. Front Psychiatry, 2020;11:581061.
- Dawidowski B, Grelecki G, Biłgorajski A, Podwalski P, Misiak B, Samochowiec J. Effect of Antipsychotic Treatment on Neutrophil-to-Lymphocyte Ratio during Hospitalization for Acute Psychosis in the Course of Schizophrenia-A Cross-Sectional Retrospective Study. J Clin Med, 2021;11(1):232.
- Stefanović V, Mihajlović G, Nenadović M, Dejanović SD, Borovcanin M, Trajković G. The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia. Vojnosanit Pregl, 2015; 72(12):1085-92.
- Steiner J, Frodl T, Schiltz K, Dobrowolny H, Jacobs R, Fernandes BS, et al. 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
- Semiz M, Yildirim O, Canan F, Demir S, Hasbek E, Tuman TC, Kayka N, Tosun M. Elevated neutrophil/lymphocyte ratio in patients with schizophrenia. Psychiatr Danub, 2014; (3):220-225.
- Özdin S, Böke Ö. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in different stages of schizophrenia. Psychiatry Res, 2019;271:131-135.
- Fang SH, Suzuki K, Lim CL, Chung MS, Ku PW, Chen LJ. Associations between sleep quality and inflammatory markers in patients with schizophrenia. Psychiatry Res, 2016;246:154-160.
- Lestra V, Romeo B, Martelli C, Benyamina A, Hamdani N. Could CRP be a differential biomarker of illness stages in schizophrenia? A systematic review and meta-analysis. Schizophr Res, 2022;246:175-186.
Şizofreni Hastalarında Hastaneye Yatış Sürecinde Periferik İnflamatuvar Belirteçlerdeki Değişimlerin Boylamsal Değerlendirmesi
Abstract
Amaç: Şizofreni hastalarında hastane bakımı ile sağlanan düzenli ilaç uygulaması, diyet, uyku ve fiziksel aktivitenin inflamatuar belirteçler üzerindeki etkilerini değerlendirmektir. Çalışmamızın temel hipotezi, hastane bakımının düşük dereceli inflamasyonu kısa sürede azaltacağıdır.
Gereç ve Yöntemler: Bu retrospektif boylamsal çalışmaya, dışlama ve dahil etme kriterlerini karşılayan şizofreni tanılı toplam 106 hasta dahil edildi. Nötrofil-lenfosit oranları (NLO), monosit-lenfosit oranları (MLO), trombosit-lenfosit oranları (TLO), C-reaktif protein-albumin oranları (CAO) ve sistemik immün inflamasyon indeksleri (Sİİ) gibi inflamatuar belirteçler hastaneye kabul sırasında ve üç hafta sonra hesaplanmıştır.
Bulgular: Katılımcıların yaş ortalaması 39,0±13,1 olup büyük çoğunluğu erkekti (n:75). Tüm inflamatuar belirteçlerde üç hafta sonra düşüş olduğu gözlendi. CRP, ortanca değeri 2,6'dan (çeyrekler arası aralık: 1,1-5,3) 1,90'a (çeyrekler arası aralık: 0,85-3,30) (p=0,001, etki büyüklüğü=0,375), CAO, 0.064'ten (çeyrekler arası aralık: 0.026-0.115) 0.043'e (çeyrekler arası aralık: 0.017-0.077) (p=0.005, etki büyüklüğü=0.371), NLO, 2.31'den (çeyrekler arası aralık: 1.73-3.24) 1.73'e (çeyrekler arası aralık: 1.28-2.27) (p<0.001, etki büyüklüğü=0.647), Sİİ, 634'ten (çeyrekler arası aralık: 425-870) 470'e (çeyrekler arası aralık: 321-645) (p<0.001, etki büyüklüğü=0.577), TLO, 9.85'ten (çeyrekler arası aralık: 7.4-12.7) 8.21'e (çeyrekler arası aralık: 6.22-10.3) (p<0.001, etki büyüklüğü=0.547) ve son olarak MLO, 0,297'den (çeyrekler arası aralık: 0,221-0,378) 0,258'e (çeyrekler arası aralık: 0,195-0,319) (p<0,001, etki büyüklüğü=0,522) düşmüş olduğu bulundu.
Sonuç: Bu çalışma, şizofreni hastalarında düzenli antipsikotik tedavi ve hastane bakımının NLO, MLO, TLO, Sİİ ve CAR gibi inflamasyon belirteçlerini azaltmadaki etkisinin altını çizmektedir. Gelecekteki çalışmalar, CAR ve SII gibi belirteçlerin düşük dereceli inflamasyonu tespit etme potansiyelini araştırmalı ve kapsamlı hastane bakımının önemli rollerinden düzenli uyku, beslenme ve fiziksel aktivitenin rolleri daha fazla araştırmalıdır.
Keywords
şizofreni düşük dereceli inflamasyon antipsikotikler sistemik immün inflamasyon indeksi C-reaktif protein (CRP) albumin oranı (CAR)
References
- Soygür H. The concept of schizophrenia: ‘’Shall we destroy and rebuild, repair and update?’’ Update in Psychiatry, 2023; 13(1):1-9.
- Ermakov EA, Melamud MM, Buneva VN, Ivanova SA. Immune system abnormalities in schizophrenia: An integrative view and translational perspectives. Front Psychiatry, 2022; 25(13):880568.
- Zhu X, Zhou J, Zhu Y, Yan F, Han X, Tan Y, Li R. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia. Australas Psychiatry, 2022; 30(1):95-99.
- Tsai SJ. Role of interleukin 8 in depression and other psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry, 2021; 106:110173.
- 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.
- Jarskog LF, Xiao H, Wilkie MB, Lauder JM, Gilmore JH. Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro. Int J Dev Neurosci. 1997 Oct;15(6):711-716.
- Rodrigues-Amorim D, Rivera-Baltanás T, Spuch C, Caruncho HJ, González-Fernandez Á, Olivares JM, et al. Cytokines dysregulation in schizophrenia: A systematic review of psychoneuroimmune relationship. Schizophr Res, 2018; 197:19-33.
- Bulut NS, Yorguner N, Çarkaxhiu Bulut G. 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, 2021; 75(8):624-632.
- Inanli I, Aydin M, Çaliskan AM, Eren I. Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder. Nord J Psychiatry. 2019;73(6):372-379.
- Huang K, Tang Y, Chen Z, Ding S, Zeng H, Zhao Y, Yu Q, Liu Y. Comparison of hematological parameters between first-episode schizophrenia and anti-NMDAR encephalitis. Front Cell Dev Biol, 2022; 10:895178.
- Mazza MG, Lucchi S, Rossetti A, Clerici M. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in non-affective psychosis: A meta-analysis and systematic review. World J Biol Psychiatry, 2020; 21(5):326-338.
- Šagud M, Madžarac Z, Nedic Erjavec G, Šimunović Filipčić I, Mikulić FL, Rogić D, et al. The associations of neutrophil-lymphocyte, platelet-lymphocyte, monocyte-lymphocyte ratios and immune-inflammation index with negative symptoms in patients with schizophrenia. Biomolecules, 2023; 13(2):297.
- Inaltekin A, Yağci İ. Evaluation of simple markers of inflammation and systemic immune inflammation index in schizophrenia, bipolar disorder patients and healthy controls. Turk Psikiyatri Derg, 2023; 34(1):11-15.
- Ranzani OT, Zampieri FG, Forte DN, Azevedo LC, Park M. C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One. 2013;8(3):e59321.
- Balcioglu YH, Kirlioglu SS. C-Reactive Protein/Albumin and Neutrophil/Albumin Ratios as Novel Inflammatory Markers in Patients with Schizophrenia. Psychiatry Investig, 2020; 17(9):902-910.
- Balcioglu YH, Balcioglu SSK, Oncu F, Turkcan A, Yorulmaz AC. Impulsive and aggressive traits and increased peripheral inflammatory status as psychobiological substrates of homicide behavior in schizophrenia. The European Journal of Psychiatry, 2022; 36(3), 207-214.
- Karageorgiou V, Milas GP, Michopoulos I. Neutrophil-to-lymphocyte ratio in schizophrenia: A systematic review and meta-analysis. Schizophr Res, 2019; 206:4-12.
- American Psychiatric Association: Desk Reference to the Diagnostic Criteria From DSM-5. Arlington, VA, American Psychiatric Association, 2013.
- Sisman AR, Kume T, Akan P, Tuncel P. C-reactive protein: Clinical significance, improvements in methodology, pre-analytical and analytical variations. Türk Klinik Biyokimya Derg, 2007; 5(1): 33-41.
- Zhou X, Wang X, Li R, Yan J, Xiao Y, Li W, et al. Neutrophil-to-Lymphocyte Ratio Is Independently Associated With Severe Psychopathology in Schizophrenia and Is Changed by Antipsychotic Administration: A Large-Scale Cross-Sectional Retrospective Study. Front Psychiatry, 2020;11:581061.
- Dawidowski B, Grelecki G, Biłgorajski A, Podwalski P, Misiak B, Samochowiec J. Effect of Antipsychotic Treatment on Neutrophil-to-Lymphocyte Ratio during Hospitalization for Acute Psychosis in the Course of Schizophrenia-A Cross-Sectional Retrospective Study. J Clin Med, 2021;11(1):232.
- Stefanović V, Mihajlović G, Nenadović M, Dejanović SD, Borovcanin M, Trajković G. The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia. Vojnosanit Pregl, 2015; 72(12):1085-92.
- Steiner J, Frodl T, Schiltz K, Dobrowolny H, Jacobs R, Fernandes BS, et al. 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
- Semiz M, Yildirim O, Canan F, Demir S, Hasbek E, Tuman TC, Kayka N, Tosun M. Elevated neutrophil/lymphocyte ratio in patients with schizophrenia. Psychiatr Danub, 2014; (3):220-225.
- Özdin S, Böke Ö. Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in different stages of schizophrenia. Psychiatry Res, 2019;271:131-135.
- Fang SH, Suzuki K, Lim CL, Chung MS, Ku PW, Chen LJ. Associations between sleep quality and inflammatory markers in patients with schizophrenia. Psychiatry Res, 2016;246:154-160.
- Lestra V, Romeo B, Martelli C, Benyamina A, Hamdani N. Could CRP be a differential biomarker of illness stages in schizophrenia? A systematic review and meta-analysis. Schizophr Res, 2022;246:175-186.
Details
| Primary Language | English |
|---|---|
| Subjects | Psychiatry |
| Journal Section | Original Article |
| Authors | |
| Early Pub Date | December 29, 2023 |
| Publication Date | December 31, 2023 |
| Submission Date | July 18, 2023 |
| Published in Issue | Year 2023 Volume: 33 Issue: 6 |
Journal of General Medicine is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY NC).