The International Journal of Neuropsychopharmacology

Research Article

Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder

Marcia Kauer-Sant'Annaa1a2, Flávio Kapczinskia3, Ana C. Andreazzaa1a2, David J. Bonda1, Raymond W. Lama1, L. Trevor Younga1 and Lakshmi N. Yathama1 c1

a1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada

a2 Post-Graduate Biochemistry Program, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

a3 Molecular Psychiatry Research Unit, Federal University of Rio Grande do Sul, and Bipolar Disorders Program, Hospital de Clinicas do Porto Alegre, Porto Alegre, Brazil


Bipolar I disorder (BD) has a poorer longer-term outcome than previously thought, with persistent cognitive impairment and functional decline. The neurobiological underpinnings that might underlie these changes remain unknown. Changes in brain-derived neurotrophic factor (BDNF) levels and cytokines are potential candidates. The aim of this study was to examine both cytokine and BDNF levels and their relationship in BD patients in the early and late stages of the disorder. We measured serum BDNF, TNF-α, IL-6 and IL-10 levels in a total of 60 patients with BD I and we compared those in early stages of illness with those in late stages of illness and also compared both groups with 60 matched healthy controls. BDNF was decreased only in those patients in the late stage of bipolar disorder. Moreover, BDNF levels were negatively correlated with length of illness. In contrast, all interleukins and TNF-α were increased in the early stages of BD, compared to controls. While TNF-α and IL-6 continued to be significantly higher than controls at late stages of BD, IL-10 did not. When levels were compared between patients at early and late stages of illness, there was a significant decrease in BDNF and IL-6 in the later stage of BD compared to the early stage. Inversely, TNF-α showed a significant increase at the later stage. Failure of inflammatory defences in the late stage of the disorder may account for reduction in BDNF and continued elevations in cytokines; thus these may have the potential to serve as markers of illness progression in BD.

(Received May 24 2008)

(Reviewed June 26 2008)

(Revised July 24 2008)

(Accepted July 28 2008)

(Online publication September 04 2008)


c1 Address for correspondence: L. N. Yatham, MBBS, FRCPC, MRCPsych (UK), Professor of Psychiatry and Associate Head, Research and International Affairs Department of Psychiatry, University of British Columbia, Room 2C7, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1 Canada. Tel.: 1-604-822-7325 Fax: 1-604-822-7922 E-mail: