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Published in: BMC Psychiatry 1/2012

Open Access 01-12-2012 | Research article

Plasma concentrations of soluble cytokine receptors in euthymic bipolar patients with and without subsyndromal symptoms

Authors: Turan Cetin, Sinan Guloksuz, Esin Aktas Cetin, Sema Bilgic Gazioglu, Gunnur Deniz, E Timucin Oral, Jim van Os

Published in: BMC Psychiatry | Issue 1/2012

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Abstract

Background

Current evidence suggests that high concentrations of pro-inflammatory markers are associated with bipolar disorder characterized by severe impairment during inter-episodic periods, reduced treatment response and persistent subsyndromal symptoms. We tested whether persistent subsyndromal symptoms in euthymic bipolar patients were associated with markers of an ongoing chronic pro-inflammatory process.

Methods

Forty-five euthymic bipolar patients (22 with subsyndromal symptoms (BD+) and 23 without subsyndromal symptoms (BD-) and 23 well controls (WC) were recruited for assessment of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R) and soluble interleukin-2 receptor (sIL-2R) concentrations. Soluble cytokine receptor concentrations were assessed using enzyme-linked immunosorbent assay.

Results

In comparison to WC, sTNF-R1 concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.34, p = 0.012 and β = 0.41, p = 0.003). Similarly, compared to WC, sIL-6R concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.44, p = 0.001 and β = 0.37, p = 0.008). There was no difference between BD- and BD+ in the concentration of either sTNF-R1 or sIL-6R; plasma concentration of sIL-2R was not analyzed as 75% percent of the samples were non-detectable.

Conclusions

Although bipolar patients present with a pro-inflammatory shift compared to well controls, subsyndromal symptoms are not associated with additive increasing effects. Longitudinal studies with larger samples are required to clarify the relationship between illness course and inflammatory markers in bipolar disorder.
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Literature
1.
go back to reference Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB: A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003, 60 (3): 261-269. 10.1001/archpsyc.60.3.261.CrossRefPubMed Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB: A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003, 60 (3): 261-269. 10.1001/archpsyc.60.3.261.CrossRefPubMed
2.
go back to reference Marangell LB: The importance of subsyndromal symptoms in bipolar disorder. J Clin Psychiatry. 2004, 65 (Suppl 10): 24-27.PubMed Marangell LB: The importance of subsyndromal symptoms in bipolar disorder. J Clin Psychiatry. 2004, 65 (Suppl 10): 24-27.PubMed
3.
go back to reference Marangell LB, Dennehy EB, Miyahara S, Wisniewski SR, Bauer MS, Rapaport MH, Allen MH: The functional impact of subsyndromal depressive symptoms in bipolar disorder: data from STEP-BD. J Affect Disord. 2009, 114 (1–3): 58-67.CrossRefPubMed Marangell LB, Dennehy EB, Miyahara S, Wisniewski SR, Bauer MS, Rapaport MH, Allen MH: The functional impact of subsyndromal depressive symptoms in bipolar disorder: data from STEP-BD. J Affect Disord. 2009, 114 (1–3): 58-67.CrossRefPubMed
4.
go back to reference Montoya A, Tohen M, Vieta E, Casillas M, Chacon F, Polavieja P, Gilaberte I: Functioning and symptomatic outcomes in patients with bipolar I disorder in syndromal remission: a 1-year, prospective, observational cohort study. J Affect Disord. 2010, 127 (1–3): 50-57.CrossRefPubMed Montoya A, Tohen M, Vieta E, Casillas M, Chacon F, Polavieja P, Gilaberte I: Functioning and symptomatic outcomes in patients with bipolar I disorder in syndromal remission: a 1-year, prospective, observational cohort study. J Affect Disord. 2010, 127 (1–3): 50-57.CrossRefPubMed
5.
go back to reference Goldstein BI, Kemp DE, Soczynska JK, McIntyre RS: Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J Clin Psychiatry. 2009, 70 (8): 1078-1090. 10.4088/JCP.08r04505.CrossRefPubMed Goldstein BI, Kemp DE, Soczynska JK, McIntyre RS: Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. J Clin Psychiatry. 2009, 70 (8): 1078-1090. 10.4088/JCP.08r04505.CrossRefPubMed
6.
go back to reference Soczynska JK, Kennedy SH, Goldstein BI, Lachowski A, Woldeyohannes HO, McIntyre RS: The effect of tumor necrosis factor antagonists on mood and mental health-associated quality of life: novel hypothesis-driven treatments for bipolar depression?. Neurotoxicology. 2009, 30 (4): 497-521. 10.1016/j.neuro.2009.03.004.CrossRefPubMed Soczynska JK, Kennedy SH, Goldstein BI, Lachowski A, Woldeyohannes HO, McIntyre RS: The effect of tumor necrosis factor antagonists on mood and mental health-associated quality of life: novel hypothesis-driven treatments for bipolar depression?. Neurotoxicology. 2009, 30 (4): 497-521. 10.1016/j.neuro.2009.03.004.CrossRefPubMed
7.
go back to reference Kronfol Z, Remick DG: Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry. 2000, 157 (5): 683-694. 10.1176/appi.ajp.157.5.683.CrossRefPubMed Kronfol Z, Remick DG: Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry. 2000, 157 (5): 683-694. 10.1176/appi.ajp.157.5.683.CrossRefPubMed
8.
go back to reference Brietzke E, Stertz L, Fernandes BS, Kauer-Sant'anna M, Mascarenhas M, Escosteguy Vargas A, Chies JA, Kapczinski F: Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009, 116 (3): 214-217. 10.1016/j.jad.2008.12.001.CrossRefPubMed Brietzke E, Stertz L, Fernandes BS, Kauer-Sant'anna M, Mascarenhas M, Escosteguy Vargas A, Chies JA, Kapczinski F: Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009, 116 (3): 214-217. 10.1016/j.jad.2008.12.001.CrossRefPubMed
9.
go back to reference Guloksuz S, Cetin EA, Cetin T, Deniz G, Oral ET, Nutt DJ: Cytokine levels in euthymic bipolar patients. J Affect Disord. 2010, 126 (3): 458-462. 10.1016/j.jad.2010.04.027.CrossRefPubMed Guloksuz S, Cetin EA, Cetin T, Deniz G, Oral ET, Nutt DJ: Cytokine levels in euthymic bipolar patients. J Affect Disord. 2010, 126 (3): 458-462. 10.1016/j.jad.2010.04.027.CrossRefPubMed
10.
go back to reference Kunz M, Cereser KM, Goi PD, Fries GR, Teixeira AL, Fernandes BS, Belmonte-de-Abreu PS, Kauer-Sant'Anna M, Kapczinski F, Gama CS: Serum levels of IL-6, IL-10 and TNF-alpha in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance. Rev Bras Psiquiatr. 2011, 33 (3): 268-274. 10.1590/S1516-44462011000300010.CrossRefPubMed Kunz M, Cereser KM, Goi PD, Fries GR, Teixeira AL, Fernandes BS, Belmonte-de-Abreu PS, Kauer-Sant'Anna M, Kapczinski F, Gama CS: Serum levels of IL-6, IL-10 and TNF-alpha in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance. Rev Bras Psiquiatr. 2011, 33 (3): 268-274. 10.1590/S1516-44462011000300010.CrossRefPubMed
11.
go back to reference Kapczinski F, Dal-Pizzol F, Teixeira AL, Magalhaes PV, Kauer-Sant'Anna M, Klamt F, Moreira JC, de Bittencourt Pasquali MA, Fries GR, Quevedo J, et al: Peripheral biomarkers and illness activity in bipolar disorder. J Psychiatr Res. 2011, 45 (2): 156-161. 10.1016/j.jpsychires.2010.05.015.CrossRefPubMed Kapczinski F, Dal-Pizzol F, Teixeira AL, Magalhaes PV, Kauer-Sant'Anna M, Klamt F, Moreira JC, de Bittencourt Pasquali MA, Fries GR, Quevedo J, et al: Peripheral biomarkers and illness activity in bipolar disorder. J Psychiatr Res. 2011, 45 (2): 156-161. 10.1016/j.jpsychires.2010.05.015.CrossRefPubMed
12.
go back to reference Guloksuz S, Altinbas K, Aktas Cetin E, Kenis G, Bilgic Gazioglu S, Deniz G, Oral ET, van Os J: Evidence for an association between tumor necrosis factor-alpha levels and lithium response. J Affect Disord. 2012, 10.1016/j.jad.2012.04.044. Guloksuz S, Altinbas K, Aktas Cetin E, Kenis G, Bilgic Gazioglu S, Deniz G, Oral ET, van Os J: Evidence for an association between tumor necrosis factor-alpha levels and lithium response. J Affect Disord. 2012, 10.1016/j.jad.2012.04.044.
13.
go back to reference Kapczinski F, Dias VV, Kauer-Sant'Anna M, Brietzke E, Vazquez GH, Vieta E, Berk M: The potential use of biomarkers as an adjunctive tool for staging bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2009, 33 (8): 1366-1371. 10.1016/j.pnpbp.2009.07.027.CrossRefPubMed Kapczinski F, Dias VV, Kauer-Sant'Anna M, Brietzke E, Vazquez GH, Vieta E, Berk M: The potential use of biomarkers as an adjunctive tool for staging bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2009, 33 (8): 1366-1371. 10.1016/j.pnpbp.2009.07.027.CrossRefPubMed
14.
go back to reference Post RM, Fleming J, Kapczinski F: Neurobiological correlates of illness progression in the recurrent affective disorders. J Psychiatr Res. 2012, 46 (5): 561-573. 10.1016/j.jpsychires.2012.02.004.CrossRefPubMed Post RM, Fleming J, Kapczinski F: Neurobiological correlates of illness progression in the recurrent affective disorders. J Psychiatr Res. 2012, 46 (5): 561-573. 10.1016/j.jpsychires.2012.02.004.CrossRefPubMed
15.
go back to reference Munkholm K, Vinberg M, Vedel Kessing L: Cytokines in bipolar disorder: A systematic review and meta-analysis. J Affect Disord. 2012, 10.1016/j.jad.2012.06.010. Munkholm K, Vinberg M, Vedel Kessing L: Cytokines in bipolar disorder: A systematic review and meta-analysis. J Affect Disord. 2012, 10.1016/j.jad.2012.06.010.
16.
go back to reference Tirpan K, Ozerdem A, Tunca Z, Yazici O, Oral ET, Kurt E, Vahip S: A computerized registry program for bipolar illness in Turkey. J Affect Disord. 2004, 78 (suppl): 126-127. Tirpan K, Ozerdem A, Tunca Z, Yazici O, Oral ET, Kurt E, Vahip S: A computerized registry program for bipolar illness in Turkey. J Affect Disord. 2004, 78 (suppl): 126-127.
17.
go back to reference Sachs GS, Thase ME, Otto MW, Bauer M, Miklowitz D, Wisniewski SR, Lavori P, Lebowitz B, Rudorfer M, Frank E, et al: Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003, 53 (11): 1028-1042. 10.1016/S0006-3223(03)00165-3.CrossRefPubMed Sachs GS, Thase ME, Otto MW, Bauer M, Miklowitz D, Wisniewski SR, Lavori P, Lebowitz B, Rudorfer M, Frank E, et al: Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003, 53 (11): 1028-1042. 10.1016/S0006-3223(03)00165-3.CrossRefPubMed
18.
go back to reference Barbosa IG, Huguet RB, Mendonca VA, Sousa LP, Neves FS, Bauer ME, Teixeira AL: Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2011, 261 (2): 139-143. 10.1007/s00406-010-0116-z.CrossRefPubMed Barbosa IG, Huguet RB, Mendonca VA, Sousa LP, Neves FS, Bauer ME, Teixeira AL: Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2011, 261 (2): 139-143. 10.1007/s00406-010-0116-z.CrossRefPubMed
19.
go back to reference Barbosa IG, Rocha NP, de Miranda AS, Magalhaes PV, Huguet RB, de Souza LP, Kapczinski F, Teixeira AL: Increased levels of adipokines in bipolar disorder. J Psychiatr Res. 2012, 46 (3): 389-393. 10.1016/j.jpsychires.2011.11.010.CrossRefPubMed Barbosa IG, Rocha NP, de Miranda AS, Magalhaes PV, Huguet RB, de Souza LP, Kapczinski F, Teixeira AL: Increased levels of adipokines in bipolar disorder. J Psychiatr Res. 2012, 46 (3): 389-393. 10.1016/j.jpsychires.2011.11.010.CrossRefPubMed
20.
go back to reference Leonard B, Maes M: Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev. 2012, 36 (2): 764-785. 10.1016/j.neubiorev.2011.12.005.CrossRefPubMed Leonard B, Maes M: Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev. 2012, 36 (2): 764-785. 10.1016/j.neubiorev.2011.12.005.CrossRefPubMed
21.
go back to reference Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008, 9 (1): 46-56. 10.1038/nrn2297.CrossRefPubMedPubMedCentral Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008, 9 (1): 46-56. 10.1038/nrn2297.CrossRefPubMedPubMedCentral
22.
go back to reference Brietzke E, Kapczinski F: TNF-alpha as a molecular target in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32 (6): 1355-1361. 10.1016/j.pnpbp.2008.01.006.CrossRefPubMed Brietzke E, Kapczinski F: TNF-alpha as a molecular target in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32 (6): 1355-1361. 10.1016/j.pnpbp.2008.01.006.CrossRefPubMed
23.
go back to reference Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, Pollmacher T: Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999, 33 (5): 407-418. 10.1016/S0022-3956(99)00021-7.CrossRefPubMed Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, Pollmacher T: Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res. 1999, 33 (5): 407-418. 10.1016/S0022-3956(99)00021-7.CrossRefPubMed
24.
go back to reference Barbosa IG, Rocha NP, Huguet RB, Ferreira RA, Salgado JV, Carvalho LA, Pariante CM, Teixeira AL: Executive dysfunction in euthymic bipolar disorder patients and its association with plasma biomarkers. J Affect Disord. 2012, 137 (1–3): 151-155.CrossRefPubMed Barbosa IG, Rocha NP, Huguet RB, Ferreira RA, Salgado JV, Carvalho LA, Pariante CM, Teixeira AL: Executive dysfunction in euthymic bipolar disorder patients and its association with plasma biomarkers. J Affect Disord. 2012, 137 (1–3): 151-155.CrossRefPubMed
25.
go back to reference Kauer-Sant'Anna M, Kapczinski F, Andreazza AC, Bond DJ, Lam RW, Young LT, Yatham LN: Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder. Int J Neuropsychopharmacol. 2009, 12 (4): 447-458. 10.1017/S1461145708009310.CrossRefPubMed Kauer-Sant'Anna M, Kapczinski F, Andreazza AC, Bond DJ, Lam RW, Young LT, Yatham LN: Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder. Int J Neuropsychopharmacol. 2009, 12 (4): 447-458. 10.1017/S1461145708009310.CrossRefPubMed
26.
go back to reference Tohen M, Frank E, Bowden CL, Colom F, Ghaemi SN, Yatham LN, Malhi GS, Calabrese JR, Nolen WA, Vieta E, et al: The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord. 2009, 11 (5): 453-473. 10.1111/j.1399-5618.2009.00726.x.CrossRefPubMed Tohen M, Frank E, Bowden CL, Colom F, Ghaemi SN, Yatham LN, Malhi GS, Calabrese JR, Nolen WA, Vieta E, et al: The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord. 2009, 11 (5): 453-473. 10.1111/j.1399-5618.2009.00726.x.CrossRefPubMed
Metadata
Title
Plasma concentrations of soluble cytokine receptors in euthymic bipolar patients with and without subsyndromal symptoms
Authors
Turan Cetin
Sinan Guloksuz
Esin Aktas Cetin
Sema Bilgic Gazioglu
Gunnur Deniz
E Timucin Oral
Jim van Os
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2012
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-12-158

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