High mobility group box-1 levels in Schizophrenia

  • Nuryil Yilmaz Cumhuriyet University Faculty of Medicine
  • Zekeriya Yelboga Cumhuriyet University Faculty of Medicine Department of Psychiatry
  • Yavuz Yilmaz Cumhuriyet University Faculty of Medicine, Department of Psychiatry
  • Ozlem Demirpence
Keywords: schizophrenia, HMGB-1, Remission and acute exacerbation phase.


Background: Schizophrenia is a chronic mental disorder, characterized by acute exacerbation and remission phases. Immune system has a role in the pathophysiology of schizophrenia. High mobility group box-1 (HMGB-1)  is a macrophage secreted protein activating immune cells to produce cytokines. The aim of this study was to evaluate HMGB-1 levels among patients with schizophrenia both in acute exacerbation and remission phases.

Methods: Consecutive schizophrenia patients in acute exacerbation and remission phases were enrolled and compared with each other and with age-sex matched healthy subjects. Patients were assessed with the Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale (CGI).

Results: Mean HMGB-1 levels were not significantly different in acute exacerbation phase versus remission phase schizophrenia patients (2139±564 pg/ml vs. 2326±471 pg/ml, p=0.335) and both were individually higher than the control group (1791±444 pg/ml, p=0.05 for acute exacerbation vs control, p=0.002 for remission vs control). In remission phase schizophrenic patients, HMGB-1 levels were positively correlated with Scale For The Assessment of Positive Symptoms (r=0.447, p=0.015) and BPRS (r=0.397, p=0.033) scores and HMGB-1 levels were independently associated with BPRS.

Conclusion: Serum HMGB-1 levels were shown to be increased in patients with schizophrenia patients irrespective of phase and HMGB-1 levels were related to symptom severity according to psychiatric scales among patients in remission phase of schizophrenia.



1. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:277-86.
2. Ozbey U, Tug E, Kara M, Namli M. The value of interleukin-12B (p40) gene promoter polymorphism in patients with schizophrenia in a region of East Turkey. Psychiatry Clin Neurosci. 2008;62(3):307-12.
3. Watanabe Y, Someya T, Nawa H. Cytokine hypothesis of schizophrenia pathogenesis: evidence from human studies and animal models. Psychiatry Clin Neurosci. 2010;64(3):217-30.
4. Altamura AC, Pozzoli S, Fiorentini A, Dell'osso B. Neurodevelopment and inflammatory patterns in schizophrenia in relation to pathophysiology. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:63-70.
5. Garcia-Bueno B, Bioque M, Mac-Dowell KS, Barcones MF, Martinez-Cengotitabengoa M, Pina-Camacho L, et al. Pro-/anti-inflammatory dysregulation in patients with first episode of psychosis: toward an integrative inflammatory hypothesis of schizophrenia. Schizophr Bull. 2014;40(2):376-87.
6. 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):663-71.
7. Yamada S, Maruyama I. HMGB1, a novel inflammatory cytokine. Clin Chim Acta. 2007;375(1-2):36-42.
8. Yang H, Tracey KJ. Targeting HMGB1 in inflammation. Biochim Biophys Acta. 2010;1799(1-2):149-56.
9. Park JS, Arcaroli J, Yum HK, Yang H, Wang H, Yang KY, et al. Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol Cell Physiol. 2003;284(4):C870-9.
10. Magna M, Pisetsky DS. The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med. 2014;20:138-46.
11. Andreasen NC. Methods for assessing positive and negative symptoms. Mod Probl Pharmacopsychiatry. 1990;24:73-88.
12. Overall JE. The Brief Psychiatric Rating-Scale (Bprs) - Recent Developments in Ascertainment and Scaling - Introduction. Psychopharmacology Bulletin. 1988;24(1):97-9.
13. Beneke M, Rasmus W. Clinical Global Impressions (Ecdeu) - Some Critical Comments. Pharmacopsychiatry. 1992;25(4):171-6.
14. Bedrossian N, Haidar M, Fares J, Kobeissy FH, Fares Y. Inflammation and Elevation of Interleukin-12p40 in Patients with Schizophrenia. Front Mol Neurosci. 2016;9:16.
15. Xiu MH, Lin CG, Tian L, Tan YL, Chen J, Chen S, et al. Increased IL-3 serum levels in chronic patients with schizophrenia: Associated with psychopathology. Psychiatry Res. 2015;229(1-2):225-9.
16. Borovcanin M, Jovanovic I, Dejanovic SD, Radosavljevic G, Arsenijevic N, Lukic ML. Increase systemic levels of IL-23 as a possible constitutive marker in schizophrenia. Psychoneuroendocrinology. 2015;56:143-7.
17. Zhu Q, Li X, Hie G, Yuan X, Lu L, Song X. [Analysis of the changes of serum high mobility group protein B1 and cytokines in first-episode schizophrenia patients]. Zhonghua Yi Xue Za Zhi. 2015;95(47):3818-22.
18. Lee EE, Hong SZ, Martin AS, Eyler LT, Jeste DV. Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables. American Journal of Geriatric Psychiatry. 2017;25(1):50-61.
19. Stojanovic A, Martorell L, Montalvo L, Ortega L, Monseny R, Vilella E, et al. Increased serum interleukin-6 levels in early stages of psychosis: Associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology. 2014;41:23-32.
20. Borovcanin M, Jovanovic I, Radosavljevic G, Dejanovic SD, Stefanovic V, Arsenijevic N, et al. Antipsychotics can modulate the cytokine profile in schizophrenia: Attenuation of the type-2 inflammatory response. Schizophrenia Research. 2013;147(1):103-9.
21. Weber MD, Frank MG, Tracey KJ, Watkins LR, Maier SF. Stress induces the danger-associated molecular pattern HMGB-1 in the hippocampus of male Sprague Dawley rats: a priming stimulus of microglia and the NLRP3 inflammasome. J Neurosci. 2015;35(1):316-24.
22. Yao X, Jiang Q, Ding W, Yue P, Wang J, Zhao K, et al. Interleukin 4 inhibits high mobility group box-1 protein-mediated NLRP3 inflammasome formation by activating peroxisome proliferator-activated receptor-gamma in astrocytes. Biochem Biophys Res Commun. 2019;509(2):624-31.
23. Lee EE, Hong S, Martin AS, Eyler LT, Jeste DV. Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables. Am J Geriatr Psychiatry. 2017;25(1):50-61.
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