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Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder

Published online by Cambridge University Press:  07 December 2017

Ole Köhler-Forsberg Open the ORCID record for Ole Köhler-Forsberg [Opens in a new window] ,
Louisa Sylvia ,
Thilo Deckersbach ,
Michael Joshua Ostacher ,
Melvin McInnis ,
Dan Iosifescu ,
Charles Bowden ,
Susan McElroy ,
Joseph Calabrese  and
Michael Thase
...Show all authors
Ole Köhler-Forsberg*
Affiliation:
Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
Louisa Sylvia
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA
Thilo Deckersbach
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA
Michael Joshua Ostacher
Affiliation:
VA Palo Alto Health Care System, Palo Alto, CA, USA Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Melvin McInnis
Affiliation:
Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
Dan Iosifescu
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Charles Bowden
Affiliation:
Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA
Susan McElroy
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA Lindner Center of HOPE, Mason, OH, USA
Joseph Calabrese
Affiliation:
Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA
Michael Thase
Affiliation:
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
Richard Charles Shelton
Affiliation:
Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL, USA
Mauricio Tohen
Affiliation:
Department of Psychiatry, University of New Mexico Health Science Center, Albuquerque, NM, USA
James Kocsis
Affiliation:
Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA
Edward Friedman
Affiliation:
Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Terence Ketter
Affiliation:
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Andrew Alan Nierenberg
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA
*
Ole Köhler-Forsberg, Psychosis Research Unit, Aarhus University Hospital, Risskov, Skovagervej 2, DK-8240 Risskov, Denmark. Tel: +45 2342 0661 Fax: +45 7847 1609 E-mail: [email protected]
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Abstract

Objective

Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences.

Methods

We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases.

Results

The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms.

Conclusion

Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.

Keywords

affective disorderbipolar disorderclinical trialslithiummood stabiliserspsychoneuroimmunology
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 30 , Issue 5 , October 2018 , pp. 297 - 305
Copyright
© Scandinavian College of Neuropsychopharmacology 2017 

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References

1. Drexhage, RC, Knijff, EM, Padmos, RC et al. The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Rev Neurother 2010;10:59–76.Google Scholar
2. Bai, YM, Su, TP, Tsai, SJ et al. Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/depressive states of bipolar disorder. J Affect Disord 2014;166:187–192.Google Scholar
3. Dargel, AA, Godin, O, Kapczinski, F, Kupfer, DJ, Leboyer, M. C-reactive protein alterations in bipolar disorder: a meta-analysis. J Clin Psychiatry 2015;76:142–150.Google Scholar
4. Hope, S, Dieset, I, Agartz, I et al. Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia. J Psychiatr Res 2011;45:1608–1616.Google Scholar
5. Lotrich, FE, Butters, MA, Aizenstein, H, Marron, MM, Reynolds, CF III, Gildengers, AG. The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder. Int J Geriatr Psychiatry 2014;29:635–644.Google Scholar
6. Hope, S, Ueland, T, Steen, NE et al. Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder. Schizophr Res 2013;145:36–42.Google Scholar
7. Hope, S, Hoseth, E, Dieset, I et al. Inflammatory markers are associated with general cognitive abilities in schizophrenia and bipolar disorder patients and healthy controls. Schizophr Res 2015;165:188–194.Google Scholar
8. Raison, CL, Miller, AH. Depression in cancer: new developments regarding diagnosis and treatment. Biol Psychiatry 2003;54:283–294.Google Scholar
9. Saper, CB, Romanovsky, AA, Scammell, TE. Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci 2012;15:1088–1095.Google Scholar
10. Elenkov, IJ. Neurohormonal-cytokine interactions: implications for inflammation, common human diseases and well-being. Neurochem Int 2008;52:40–51.Google Scholar
11. Krogh, J, Benros, ME, Jorgensen, MB, Vesterager, L, Elfving, B, Nordentoft, M. The association between depressive symptoms, cognitive function, and inflammation in major depression. Brain Behav Immun 2014;35:70–76.Google Scholar
12. Jokela, M, Virtanen, M, Batty, GD, Kivimaki, M. Inflammation and specific symptoms of depression. JAMA Psychiatry 2016;73:87–88.Google Scholar
13. Kohler, O, Sylvia, LG, Bowden, CL et al. White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder. Aust N Z J Psychiatry 2017;51:355–365.Google Scholar
14. Walsh, JT, Watson, N, Kipnis, J. T cells in the central nervous system: messengers of destruction or purveyors of protection? Immunology 2014;141:340–344.Google Scholar
15. Brod, S, Rattazzi, L, Piras, G, D’Acquisto, F. ‘As above, so below’ examining the interplay between emotion and the immune system. Immunology 2014;143:311–318.Google Scholar
16. Angele, MK, Pratschke, S, Hubbard, WJ, Chaudry, IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence 2014;5:12–19.Google Scholar
17. Nierenberg, AA, Sylvia, LG, Leon, AC et al. Lithium treatment – moderate dose use study (LiTMUS) for bipolar disorder: rationale and design. Clin Trials 2009;6:637–648.Google Scholar
18. Nierenberg, AA, Sylvia, LG, Leon, AC et al. Clinical and health outcomes initiative in comparative effectiveness for bipolar disorder (bipolar CHOICE): a pragmatic trial of complex treatment for a complex disorder. Clin Trials 2014;11:114–127.Google Scholar
19. Amitai, M, Zivony, A, Kronenberg, S et al. Short-term effects of lithium on white blood cell counts and on levels of serum thyroid-stimulating hormone and creatinine in adolescent inpatients: a retrospective naturalistic study. J Child Adolesc Psychopharmacol 2014;24:494–500.Google Scholar
20. Spearing, MK, Post, RM, Leverich, GS, Brandt, D, Nolen, W. Modification of the clinical global impressions (CGI) scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Res 1997;73:159–171.Google Scholar
21. Sheehan, DV, Lecrubier, Y, Sheehan, KH et al. 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 1998;59(Suppl. 20):22–33; (quiz 34–57).Google Scholar
22. Montgomery, SA, Asberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382–389.Google Scholar
23. Bowden, CL, Singh, V, Thompson, P et al. Development of the bipolar inventory of symptoms scale. Acta Psychiatr Scand 2007;116:189–194.Google Scholar
24. Gonzalez, JM, Bowden, CL, Katz, MM et al. Development of the bipolar inventory of symptoms scale: concurrent validity, discriminant validity and retest reliability. Int J Methods Psychiatr Res 2008;17:198–209.Google Scholar
25. Thompson, PM, Gonzalez, JM, Singh, V, Schoolfield, JD, Katz, MM, Bowden, CL. Principal domains of behavioral psychopathology identified by the bipolar inventory of signs and symptoms scale (BISS). Psychiatry Res 2010;175:221–226.Google Scholar
26. Kannel, WB, Anderson, K, Wilson, PW. White blood cell count and cardiovascular disease. Insights from the Framingham study. JAMA 1992;267:1253–1256.Google Scholar
27. Lally, J, MacCabe, JH. Antipsychotic medication in schizophrenia: a review. Br Med Bull 2015;114:169–179.Google Scholar
28. Liu, B, Taioli, E. Seasonal variations of complete blood count and inflammatory biomarkers in the US population – analysis of NHANES data. PLoS One 2015;10:e0142382.Google Scholar
29. Pandey, GN, Rizavi, HS, Ren, X et al. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 2012;46:57–63.Google Scholar
30. Uher, R, Tansey, KE, Dew, T et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry 2014;171:1278–1286.Google Scholar
31. Raison, CL, Rutherford, RE, Woolwine, BJ et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013;70:31–41.Google Scholar
32. Kohler, O, Benros, ME, Nordentoft, M et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 2014;71:1381–1391.Google Scholar
33. Li, H, Hong, W, Zhang, C et al. IL-23 and TGF-beta1 levels as potential predictive biomarkers in treatment of bipolar I disorder with acute manic episode. J Affect Disord 2015;174:361–366.Google Scholar
34. Ayorech, Z, Tracy, DK, Baumeister, D, Giaroli, G. Taking the fuel out of the fire: evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders. J Affect Disord 2015;174:467–478.Google Scholar
35. Arabzadeh, S, Ameli, N, Zeinoddini, A et al. Celecoxib adjunctive therapy for acute bipolar mania: a randomized, double-blind, placebo-controlled trial. Bipolar Disord 2015;17:606–614.Google Scholar
36. Horne, BD, Anderson, JL, John, JM et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005;45:1638–1643.Google Scholar
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