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

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.

Keywords: bipolar disorder; brain-derived neurotrophic factor; enzyme-linked immunosorbent assay; lithium.

Figures

Fig. 1: Brain-derived neurotrophic factor (BDNF) protein levels in transformed lymphoblasts from nonpsychiatric control subjects and lithium-responsive bipolar disorder (BD) patients (with and without 1 mM lithium treatment for 7 days) and unaffected relatives. BDNF protein levels were 36% lower in subjects with BD when compared with nonpsychiatric control subjects (*p = 0.02), and this decrease remained (33%, §p = 0.02) after lithium treatment. Lithium treatment decreased BDNF levels in both BD and control populations (†p = 0.05). BDNF protein levels were 55% lower in BD patients when compared with their unaffected relatives (+p = 0.003). All measures are expressed as mean (and standard deviation).