J Psychiatry Neurosci 2010;35(3):195-199
Sara K. Olsson, MS; Martin Samuelsson, MD; Peter Saetre, PhD; Leif Lindström, MD, PhD; Erik G. Jönsson, MD, PhD; Conny Nordin, MD, PhD; Göran Engberg, PhD; Sophie Erhardt, PhD; Mikael Landén, MD, PhD
Olsson, Engberg, Erhardt — Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm; Samuelsson,Nordin — Department of Clinical and Experimental Medicine, Section of Psychiatry, Faculty of Health Sciences, Linköping University, Linköping; Saetre, Jönsson — Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, Stockholm; Lindström — Department of Neuroscience, Section of Psychiatry, Uppsala University, Uppsala; Landén — Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, and the Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
Background: Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA). This astrocyte-derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive function. We measured the levels of KYNA in the cerebrospinal fluid (CSF) of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder.
Methods: We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high-performance liquid chromatography.
Results: Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] 0.13 v. 1.13 nM, SEM 0.09; p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteers.
Limitations: The influence of ongoing drug treatment among patients cannot be ruled out. We conducted our study during the euthymic phase of the disease.
Conclusion: Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patients. These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder.
Submitted Dec. 10, 2009; Revised Feb. 2, 2010; Accepted Feb. 2, 2010.
Acknowledgements: We dedicate this article to the memory of our dear friend Conny Nordin, who died July 5, 2008. We thank the health professionals who facilitated this study. In particular, we thank study coordinator Mrs. Martina Wennberg and research nurses Mrs. Agneta Carswärd-Kjellin, Mrs. Stina Stadler, Mrs. Hazel Holmberg-Forsyth and Mrs. Margareta Krona. We also thank Dr. Christian Johansson.
Funding: Financial support for this study was provided through the regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet, and through grants from the Hållstens Forskningsstiftelse, Swedish Brain Foundation, the Östergötland County Council, Svenska Läkaresällskapet, Karolinska Institutet, Torsten och Ragnar Söderbergs stiftelse and the Swedish Research Council (no. 2009-4046 to S.E., 2008-3822 and 2009-3068 to G.E., K2008-62x-14647-06-3 to M.L., and 2006-986 and 2006-2992 to E.G.J.). No funding sources had any role in study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.
Competing interests: None declared.
Contributors: Drs. Engberg, Erhardt, Nordin and Landén designed the study. Drs. Samuelsson, Lindström, Jönsson, Nordin and Landén acquired the data, which Drs. Saetre, Erhardt, Nordin and Landén and Ms. Olsson analyzed. Drs. Saetre, Engberg, Erhardt, Nordin and Landén and Ms. Olsson wrote the article. All authors reviewed the article and approved its publication.
Correspondence to: Dr. S. Erhardt, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; fax 46 8 31 06 22; firstname.lastname@example.org