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Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample

Molecular Psychiatry volume 10, pages 861–867 (2005)Cite this article

Abstract

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has been implicated in the neurobiology of depression. Our group has previously reported an association between a BDNF variant and childhood-onset mood disorder (COMD) in an adult sample from Pittsburgh. We hypothesize that variants at the BDNF locus are associated with COMD. Six BDNF polymorphisms were genotyped in 258 trios having juvenile probands with childhood-onset DSM-IV major depressive or dysthymic disorder. BDNF markers included the (GT)n microsatellite, Val66Met and four other single-nucleotide polymorphisms (SNPs) distributed across the BDNF gene. Family-based association and evolutionary haplotype analysis methods were used. Analysis of linkage disequilibrium (LD) revealed substantial LD among all six polymorphisms. Analyses of the Val66Met polymorphism demonstrated significant overtransmission of the val allele (χ2=7.12, d.f.=1, P=0.0076). Consistent with the pattern of LD, all other SNPs showed significant biased transmission. The (GT)n microsatellite alleles also indicated a trend towards biased transmission (170 bp: Z=2.095, P=0.036). Significant haplotypes involved Val66Met and BDNF2 (P=0.0029). In this Hungarian sample, we found all five BDNF SNPs tested and a haplotype containing the BDNF Val66Met Val allele to be associated with COMD. These results provide evidence that BDNF variants affect liability to juvenile-onset mood disorders, supported by data from two independent samples.

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Acknowledgements

We acknowledge Mary Smirniw for her administrative assistance. International Consortium members include István Benák, Dr Krisztina Kapornai, Viola Kothencné Osváth, Dr Edit Dombovári and Dr Emília Kaczvinszky from the Szeged University Medical Faculty Department for Child and Adolescent Psychiatry, Szeged; Dr Zsuzsa Tamás, Dr Júlia Gádoros, Dr Márta Besnyõ, Dr Judit Székely from Vadaskert Hospital, Budapest; Dr László Mayer from Margit Hospital, Csorna; and Dr Magdolna Gácser from Pándy Kálmán Hospital, Department for Child Psychiatry, Gyula. This work was supported by the Canadian Psychiatric Research Foundation (JS) and the AFSP (JS) and the NIMH Program Project P01 MH56193-08 (JLK, CLB, MK).

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Authors and Affiliations

  1. Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    J Strauss, N King, S Shaikh, M Lanktree & J L Kennedy

  2. Department of Psychiatry, Cell and Molecular Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada

    C L Barr

  3. Brain & Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada

    C L Barr

  4. Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    C J George, B Devlin & M Kovacs

  5. Department for Child and Adolescent Psychiatry, Szeged University, Szeged, Hungary

    Á Vetró & E Kiss

  6. Vadaskert Hospital, Budapest, Hungary

    I Baji

  7. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    M Kovacs

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Strauss, J., Barr, C., George, C. et al. Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample. Mol Psychiatry 10, 861–867 (2005). https://doi.org/10.1038/sj.mp.4001685

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