VAL66MET BDNF GENOTYPES IN MELANCHOLIC DEPRESSION: EFFECTS ON BRAIN STRUCTURE AND TREATMENT OUTCOME

Authors

  • Narcís Cardoner M.D., Ph.D.,

    Corresponding author
    1. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
    2. Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
    • Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
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  • Virginia Soria M.D., Ph.D.,

    1. Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
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  • Mònica Gratacòs M.D., Ph.D.,

    1. Center for Genomic Regulation (CRG) and UPF, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
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  • Rosa Hernández-Ribas M.D., Ph.D.,

    1. Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
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  • Jesús Pujol M.D., Ph.D.,

    1. Department of Magnetic Resonance, CRC Hospital del Mar, Barcelona, Spain
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  • Marina López-Solà Ph.D.,

    1. Department of Magnetic Resonance, CRC Hospital del Mar, Barcelona, Spain
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  • Joan Deus Ph.D.,

    1. Department of Clinical and Health Psychology, Autonomous University of Barcelona, Barcelona, Spain
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  • Mikel Urretavizcaya M.D., Ph.D.,

    1. Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
    3. Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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  • Xavier Estivill M.D., Ph.D.,

    1. Center for Genomic Regulation (CRG) and UPF, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
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  • José M. Menchón M.D., Ph.D.,

    1. Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
    3. Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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  • Carles Soriano-Mas Ph.D.

    1. Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain
    2. Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
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  • Contract grant sponsor: Psychiatry Genetics Network; Contract grant number: G03/184; Contract grant sponsor: Barcelona node of the Spanish National Genotyping Centre (CEGEN); Contract grant sponsor: Agència de Gestió d'Ajuts Universitaris i de Recerca; Contract grant number: AGAUR 2009SGR1554; Contract grant sponsor: Carlos III Health Institute; Contract grant numbers: PI05/2307, PI09/01961, PI10/01753, CP10/00604; Contract grant sponsor: CIBER; Contract grant number: CB06/03/0034.

Correspondence to: Dr. Narcís Cardoner, Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Feixa Llarga s/n, Barcelona, 08907, Spain. E-mail: ncardoner@bellvitgehospital.cat

Abstract

Background

A brain-derived neurotrophic factor (BDNF) prodomain single-nucleotide polymorphism resulting in a valine to methionine substitution (Val66Met) has been associated with depression-related phenotypes and brain alterations involving regions consistently associated with major depressive disorder (MDD).

The aim of our study was to evaluate the association of regional gray matter (GM) volume within the hippocampus and other unpredicted regions at the whole-brain level with the BDNF Val66Met polymorphism in MDD patients with melancholic features and their impact on treatment outcome.

Methods

A sample of 37 MDD inpatients was assessed with three-dimensional magnetic resonance imaging (1.5-T scanner). GM volume was analyzed with voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM5). The BDNF Val66Met variant was genotyped using SNPlex technology. MDD patients were classified according to genotype distribution under a dominant model of inheritance and thus comparing Val66 homozygotes (n = 22) versus Met66 carriers (n = 15).

Results

A significant GM volume reduction in the left hippocampus was observed in Met66 carriers. Conversely, in the same group, a volume increase in the right orbitofrontal cortex was detected. Moreover, a significant negative correlation between left hippocampal volume and days to remission was found in Val66 homozygotes, whereas right orbitofrontal volume was inversely correlated to days to remission in Met66 carriers.

Conclusions

Our results suggest that the Val66Met BDNF variant may have a differential impact on the brain structure of melancholic patients with possible treatment outcome implications.

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