BDNF protein levels are decreased in transformed lymphoblasts from lithium-responsive patients with bipolar disorder

BDNF protein levels are decreased in transformed lymphoblasts from lithium-responsive patients with bipolar disorder

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J Psychiatry Neurosci 2008;33(5):449–53

Michael Tseng, MD, PhD; Martin Alda, MD; Li Xu, MSc; Xiujun Sun, MSc; Jun-Feng Wang, PhD; Paul Grof, MD, PhD; Gustavo Turecki, MD, PhD; Guy Rouleau, MD, PhD; L. Trevor Young, MD, PhD

Tseng, Xu, Wang, Grof, Young — Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ont.; Alda — Department of Psychiatry, Dalhousie University, Halifax, NS; Turecki — Department of Psychiatry, McGill University; Rouleau — Department of Medicine, Université de Montréal, Montréal, Que.; Young — Department of Psychiatry, University of British Columbia, Vancouver, BC

Abstract

Objective: Brain-derived neurotrophic factor (BDNF) is a key factor in neuroplasticity and has been implicated in the affective disorders; studies have demonstrated elevated BDNF in patients taking lithium and other mood stabilizers. The objective of our study was to analyze BDNF in lithium-responsive patients with bipolar disorder (BD) to further understand the role of BDNF in the pathophysiology of BD.

Methods: Using enzyme-linked immunosorbent assay, we measured transformed B lymphocytes for BDNF protein.

Results: BDNF levels were 36% lower in lymphoblasts from patients with BD (n = 12), compared with matched control participants (n = 13), and 55% lower when compared with their unaffected relatives (n = 14). Lithium significantly decreased BDNF levels in patients with BD and healthy control participants, although BDNF levels remained lower (33%) in the BD group posttreatment.

Conclusion: Decreased BDNF may constitute part of the pathophysiologic process of BD in a lithium-responsive subgroup of individuals with this disease. A compensatory mechanism protecting the genetically predisposed unaffected relatives from phenotypic expression of BD is suggested.

Résumé

Objectif : Le facteur neurotrophique dérivé du cerveau (FNDC) joue un rôle clé dans la neuroplasticité et est mis en cause dans des troubles de l’affectivité. Des études ont démontré des concentrations élevées de FNDC chez les patients qui prenaient du lithium et d’autres thymorégulateurs. Nous voulions analyser la concentration de FNDC chez les patients atteints d’un trouble bipolaire (TB) répondant au lithium afin de comprendre davantage le rôle du FNDC dans la pathophysiologie du TB.

Méthodes : Nous avons mesuré par dosage immunoenzymatique les lymphocytes B transformés pour déterminer les protéines dans le FNDC.

Résultats : Les concentrations de FNDC étaient plus faibles de 36 % dans les lymphoblastes provenant de patients atteints d’un TB (n = 12) que dans ceux des participants témoins jumelés (n = 13), et 55 % moins élevés que chez les membres de leur parenté non atteints (n = 14). Le lithium a réduit considérablement les concentrations de FNDC chez les patients atteints de TB et les participants témoins en bonne santé, même si elles sont demeurées plus faibles (33 %) chez les patients atteints de TB après le traitement.

Conclusion : La diminution des concentrations de FNDC peut constituer un élément du processus pathophysiologique du TB chez un sous-groupe d’individus atteints de la maladie qui répondent au lithium. On pense qu’un mécanisme compensatoire protège contre l’expression phénotypique du TB les patients apparentés non touchés qui sont génétiquement prédisposés.


Medical subject headings: bipolar disorder; brain-derived neurotrophic factor; enzyme-linked immunosorbent assay; lithium.

Competing interests: None declared.

Submitted Oct. 26, 2007; Revised Dec. 7, 2007; Accepted Dec. 31, 2007

Contributors: Drs. Alda, Wang, Turecki, Rouleau and Young designed the study. Drs. Tseng, Alda, Xu, Sun, Grof and Rouleau collected the data, which Drs. Alda, Xu and Young analyzed. Drs. Tseng and Young wrote and reviewed the article, which Drs. Alda, Xu, Sun, Wang, Grof, Turecki and Rouleau also reviewed. All authors gave final approval for publication.

Acknowledgements: This study was supported by grant #64410 from the Canadian Institutes of Health Research.

Correspondence to: Dr. L.T. Young, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver BC V6T 2A1; fax 604 822-0399; Trevor.Young@ubc.ca