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Val66met polymorphism and serum brain-derived neurotrophic factor levels in bipolar disorder

Molecular Psychiatry volume 12, pages 230–231 (2007)Cite this article

There is strong evidence demonstrating that genetic inheritance is associated with higher susceptibility to bipolar disorder (BD), but the interaction between gene polymorphisms and biochemical changes remains largely unknown. A common polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which substitutes a valine for a methionine at the codon 66 (val66met) has been implicated to play a role in BD.1 Specifically, the BDNF val66met polymorphism is associated with susceptibility to rapid cycling2 and altered cognitive performance in BD subjects.3 Our group has recently reported that serum BDNF levels are decreased during acute manic and depressive episodes in BD patients, suggesting that the regulation of BDNF might be implicated in mood stabilization.4 Considering that the val66met polymorphism affects intracellular packaging and activity-dependent secretion of BDNF,5 and that there is a strong positive correlation between brain and serum BDNF levels,6 we have investigated whether the val66met polymorphism is associated with changes in serum BDNF levels in BD patients and normal controls. We hypothesized a priori that met carriers (met/met+val/met genotypes) would present lower levels of serum BDNF than the val/val group.

One hundred and seven Caucasian type-I bipolar patients were recruited from the Bipolar Disorders Program (Hospital de Clinicas de Porto Alegre, Brazil). Psychiatric diagnoses were carried out using the Structured Clinical Interview for DSM-IV-Axis I, and manic and depressive symptoms were assessed using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS), respectively. One hundred and thirty-seven healthy controls were matched by age, gender and education. Control subjects were non-smokers, were not on medication and had no history of major psychiatric disorders, dementia, mental retardation, cancer or tumor and no such disorders in their first-degree relatives. Ten milliliters of blood were withdrawn from each subject by venipuncture into a free-anticoagulant vacuum tube for biochemical analyses and 5 ml into an ethylene diamine tetraacetic acid (EDTA) vacuum tube for DNA analyses. BDNF serum levels were measured using a commercial kit of sandwich-ELISA according to the manufacturer's instruction (Chemicon, Temecula, CA, USA). The standard curve demonstrated a direct relationship between optical density and BDNF concentration. Total protein was measured by Lowry's method using bovine serum albumin as a standard. The genomic DNA was extracted using standard procedures and the BDNF val66met polymorphism was genotyped according to Neves-Pereira et al.7 All the assays were performed blind to the subject's status.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    J Tramontina & F Kapczinski

  2. Programa de Transtorno Bipolar, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    J Tramontina, B N Frey, A C Andreazza, A Santin & F Kapczinski

  3. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    B N Frey, A C Andreazza & F Kapczinski

  4. Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    M Zandona

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  1. J Tramontina
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Correspondence to F Kapczinski.

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Tramontina, J., Frey, B., Andreazza, A. et al. Val66met polymorphism and serum brain-derived neurotrophic factor levels in bipolar disorder. Mol Psychiatry 12, 230–231 (2007). https://doi.org/10.1038/sj.mp.4001941

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