Elevation of cerebrospinal fluid interleukin-1ß in bipolar disorder

Elevation of cerebrospinal fluid interleukin-1ß in bipolar disorder


J Psychiatry Neurosci 2011;36(2):114-8

Johan Söderlund, MD, PhD;* Sara K. Olsson, MSc;* Martin Samuelsson, MD; Lilian Walther-Jallow, PhD; Christian Johansson, MD; Sophie Erhardt, PhD; Mikael Landén, MD, PhD; Göran Engberg, PhD

Söderlund, Olsson, Erhardt, Engberg — Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm; Samuelsson — Department of Clinical and Experimental Medicine, Section of Psychiatry, Faculty of Health Sciences, Linköping University, Linköping; Walther-Jallow — Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm; Johansson, Landén — Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; Landén — Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

*These authors contributed equally to this work.


Background: In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention. Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its pathophysiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed.

Methods: We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar disorder type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system.

Results: The mean interleukin (IL)-1ß level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respect ively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1ß (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10).

Limitations: All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out.

Conclusion: Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1ß in bipolar disorder.

Submitted May 18, 2010; Revised Aug. 3, 2010; Accepted Aug. 4, 2010.

Acknowledgments: We gratefully acknowledge patients and healthy volunteers for their participation in the study and express our gratitude toward health professionals who facilitated our work. In particular, we thank study coordinator Mrs. Martina Wennberg, and research nurses Mrs. Agneta Carswärd-Kjellin and Mrs. Stina Stadler.

Competing interests: None declared.

Contributors: Drs. Söderlund, Landén, Erhardt and Engberg designed the study. Drs. Samuelsson, Walther-Jallow, Johansson, Landén and Engberg acquired the data, which Drs. Söderlund, Walther-Jallow, Landén and Engberg and Ms. Olsson analyzed. Drs. Söderlund, Landén, Erhardt and Engberg and Ms. Olsson wrote the article, which Drs. Söderlund, Samuelsson, Walther-Jallow, Johansson, Landén and Ms. Olsson critically reviewed. All author approved publication of the article.

Funding: Financial support for this study was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institutet, the Östergötland County Council, the Swedish Brain Foundation, Svenska Läkaresällskapet, Karolinska Institutet and the Swedish Research Council (Dr. Erhardt, No. 2009–4046; Dr. Engberg, 2008–3822, 2009–3068; Dr. Landén, K2008–62x-14647–06–3.

DOI: 10.1503/jpn.100080

Correspondence to: Dr. G. Engberg, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; goran.engberg@ki.se