Open Access Research article

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

Turan Cetin1, Sinan Guloksuz2*, Esin Aktas Cetin3, Sema Bilgic Gazioglu3, Gunnur Deniz3, E Timucin Oral4 and Jim van Os25

Author Affiliations

1 Research, Treatment and Training Center for Alcohol and Substance Dependence (AMATEM), Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Istanbul, Turkey

2 Department of Psychiatry and Psychology, Maastricht University Medical Centre, EURON, Maastricht, The Netherlands

3 Department of Immunology, Institute of Experimental Medicine (DETAE), Istanbul University, Istanbul, Turkey

4 Department of Psychology, Faculty of Arts and Sciences, Istanbul Commerce University, Istanbul, Turkey

5 King’s College London, King’s Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom

For all author emails, please log on.

BMC Psychiatry 2012, 12:158  doi:10.1186/1471-244X-12-158

Published: 26 September 2012



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.


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.


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.


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.

Bipolar disorder; Cytokine; Interleukin; Inflammation; Tumor necrosis factor; Euthymic; Subsyndromal; Staging; Biomarker