Skip to main content

Advertisement

SpringerLink
Log in

Chemokines in bipolar disorder: Trait or state?

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Recent evidence has suggested that inflammatory and immune mechanisms may play a role in the pathophysiology of bipolar disorder (BD). Only a few studies have assessed the profile of chemokines, a family of chemotactic cytokines related to the recruitment of leukocytes, in BD. The objective of our study was to evaluate the plasma levels of chemokines in BD patients in different mood states in comparison with healthy controls. Seventy BD type I patients (35 in euthymia and 35 in mania), and 50 healthy controls matched by age, gender, and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001), CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic regression stressed the main effect of increased plasma levels of CXCL10 (OR = 1.009, 95 % CI = 1.000–1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001–1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI = 0.990–0.999, p = 0.013) to BD. This study reinforces the view that BD is associated with an immune dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Altamura AC, Serati M, Albano A, Paoli RA, Glick ID, Dell’Osso B (2011) An epidemiologic and clinical overview of medical and psychopathological comorbidities in major psychoses. Eur Arch Psychiatry Clin Neurosci 261:489–508

    Article  PubMed  Google Scholar 

  2. Barbosa IG, Huguet RB, Mendonça VA, Sousa LP, Neves FS, Bauer ME, Teixeira AL (2011) Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci 261:139–143

    Article  PubMed  Google Scholar 

  3. Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (2011) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35:804–817

    Article  PubMed  CAS  Google Scholar 

  4. Goldstein BI, Kemp DE, Soczynska JK, McIntyre RS (2009) Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J Clin Psychiatry 70:1078–1090

    Article  PubMed  Google Scholar 

  5. Kim YK, Myint AM, Lee BH, Han CS, Lee SW, Leonard BE, Steinbusch HW (2004) T-helper types 1, 2, and 3 cytokine interactions in symptomatic manic patients. Psychiatry Res 129(3):267–272

    Article  PubMed  CAS  Google Scholar 

  6. Liu HC, Yang YY, Chou YM, Chen KP, Shen WW, Leu SJ (2004) Immunologic variables in acute mania of bipolar disorder. J Neuroimmunol 150:116–122

    Article  PubMed  CAS  Google Scholar 

  7. Drexhage RC, Hoogenboezem TH, Versnel MA, Berghout A, Nolen WA, Drexhage HA (2011) The activation of monocyte and T cell networks in patients with bipolar disorder. Brain Behav Immun 25(6):1206–1213

    Article  PubMed  CAS  Google Scholar 

  8. Nery FG, Monkul ES, Hatch JP, Fonseca M, Zunta-Soares GB, Frey BN, Bowden CL, Soares JC (2008) Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmacol 23(2):87–94

    Article  PubMed  CAS  Google Scholar 

  9. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621

    Article  PubMed  CAS  Google Scholar 

  10. Gonzalez-Perez O, Jauregui-Huerta F, Galvez-Contreras AY (2010) Immune system modulates the function of adult neural stem cells. Curr Immunol Rev 6:167–173

    Article  PubMed  CAS  Google Scholar 

  11. Adler MW, Rogers TJ (2005) Are chemokines the third major system in the brain? J Leukoc Biol 78:1204–1209

    Article  PubMed  CAS  Google Scholar 

  12. Altamura AC, Mundo E, Cattaneo E, Pozzoli S, Del’Osso B, Vergani C, Trabattoni D, Arosio B, Clerici M (2010) The MCP-1 gene (SCYA2) and mood disorders preliminary results of a case-control association study. NeuroImmunoModulation 17:126–131

    Article  PubMed  CAS  Google Scholar 

  13. Nakatani N, Hattori E, Ohnishi T, Dean B, Iwayama Y, Matsumoto I, Kato T, Osumi N, Higuchi T, Niwa S, Yoshikawa T (2006) Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation. Hum Mol Genet 15:1949–1962

    Article  PubMed  CAS  Google Scholar 

  14. O’Brien SM, Scully P, Scott LV, Dinan TG (2006) Cytokine profiles in bipolar affective disorder: focus on acutely ill patients. J Affect Disord 90:263–267

    Article  PubMed  Google Scholar 

  15. Brietzke E, Kauer-Sant’anna M, Teixeira AL, Kapczinski F (2009) Abnormalities in serum chemokine levels in euthymic patients with bipolar disorder. Brain Behav Immun 23:1079–1082

    Article  PubMed  CAS  Google Scholar 

  16. Amorim P (2000) Mini International Neuropsychiatric Interview (MINI): validação de entrevista breve para diagnóstico de transtornos mentais. Rev Bras Psiquiatr 22:106–115

    Article  Google Scholar 

  17. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:4–57

    Google Scholar 

  18. Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296

    Article  PubMed  CAS  Google Scholar 

  19. Young RC, Biggs JT, Ziegler VE, Meyer DA (1978) A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 133:429–435

    Article  PubMed  CAS  Google Scholar 

  20. Teixeira AL, Reis HJ, Nicolato R, Brito-Melo G, Correa H, Teixeira MM, Romano-Silva MA (2008) Increased serum levels of CCL11/eotaxin in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 32(3):710–714

    Article  PubMed  CAS  Google Scholar 

  21. Scalzo P, de Miranda AS, Guerra Amaral DC, de Carvalho Vilela M, Cardoso F, Teixeira AL (2011) Serum levels of chemokines in Parkinson’s disease. NeuroImmunoModulation 18:240–244

    Article  PubMed  CAS  Google Scholar 

  22. Munro BH (2005) Statistical methods for health care research, 5th edn. Lippincott/Raven Publishers, Philadelphia

    Google Scholar 

  23. Brietzke E, Stertz L, Fernandes BS, Kauer-Sant’anna M, Mascarenhas M, Escosteguy Vargas A, Chies JA, Kapczinski F (2009) Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord 116(3):214–217

    Article  PubMed  CAS  Google Scholar 

  24. Ortiz-Domínguez A, Hernández ME, Berlanga C, Gutiérrez-Mora D, Moreno J, Heinze G, Pavón L (2007) Immune variations in bipolar disorder: phasic differences. Bipolar Disord 9(6):596–602

    Article  PubMed  Google Scholar 

  25. Rothenberg ME, Hogan SP (2006) The eosinophil. Annu Rev Immunol 24:147–174

    Article  PubMed  CAS  Google Scholar 

  26. Ellman LM, Deicken RF, Vinogradov S, Kremen WS, Poole JH, Kern DM, Tsai WY, Schaefer CA, Brown AS (2010) Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8. Schizophr Res 121(1–3):46–54

    Article  PubMed  Google Scholar 

  27. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (2004) 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 65(7):940–947

    Article  PubMed  CAS  Google Scholar 

  28. Semple BD, Kossmann T, Morganti-Kossmann MC (2010) Role of chemokines in CNS health and pathology: a focus on the CCL2/CCR2 and CXCL8/CXCR2 networks. J Cereb Blood Flow Metab 30(3):459–473

    Article  PubMed  CAS  Google Scholar 

  29. Langan C, McDonald C (2009) Neurobiological trait abnormalities in bipolar disorder. Mol Psychiatry 14(9):833–846

    Article  PubMed  CAS  Google Scholar 

  30. Cavčić A, Tešović G, Gorenec L, Grgić I, Benić B, Lepej SZ (2011) Concentration gradient of CXCL10 and CXCL11 between the cerebrospinal fluid and plasma in children with enteroviral aseptic meningitis. Eur J Paediatr Neurol 15(6):502–507

    Article  PubMed  Google Scholar 

  31. Drexhage RC, Knijff EM, Padmos RC, Heul-Nieuwenhuijzen L, Beumer W, Versnel MA, Drexhage HA (2010) The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Rev Neurother 10(1):59–76

    Article  PubMed  CAS  Google Scholar 

  32. Kim YK, Jung HG, Myint AM, Kim H, Park SH (2007) Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord 104:91–95

    Article  PubMed  CAS  Google Scholar 

  33. Su KP, Leu SJ, Yang YY, Shen WW, Chou YM, Tsai SY (2002) Reduced production of interferon-gamma but not interleukin-10 in bipolar mania and subsequent remission. J Affect Disord 71:205–209

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded by the Brazilian funding agencies Fapemig and CNPq. Dr. Barbosa was the recipient of a CAPES scholarship during her sandwich doctorate in the Institute of Psychiatry, London.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Izabela Guimarães Barbosa, Rodrigo Barreto Huguet, Helton José Reis & Antônio Lúcio Teixeira

  2. Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Izabela Guimarães Barbosa, Natália Pessoa Rocha, Aline Silva de Miranda & Antônio Lúcio Teixeira

  3. Laboratório de Imunologia do Envelhecimento, Instituto de Pesquisas Biomédicas, Pontifícia Católica Universidade do Rio Grande do Sul, Porto Alegre, Brazil

    Moisés Evandro Bauer

  4. Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology (SPI-lab), Department of Psychological Medicine, Institute of Psychiatry, King’s College London, London, UK

    Patricia A. Zunszain, Mark A. Horowitz & Carmine M. Pariante

  5. Departamento de Clínica Médica da Faculdade de Medicina da UFMG, Av. Alfredo Balena, 190, Belo Horizonte, MG, 30130-100, Brazil

    Antônio Lúcio Teixeira

Authors
  1. Izabela Guimarães Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natália Pessoa Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Moisés Evandro Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aline Silva de Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rodrigo Barreto Huguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Helton José Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patricia A. Zunszain
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mark A. Horowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carmine M. Pariante
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Antônio Lúcio Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antônio Lúcio Teixeira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbosa, I.G., Rocha, N.P., Bauer, M.E. et al. Chemokines in bipolar disorder: Trait or state?. Eur Arch Psychiatry Clin Neurosci 263, 159–165 (2013). https://doi.org/10.1007/s00406-012-0327-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-012-0327-6

Keywords

Search

Navigation