Val66Met BDNF genotypes in melancholic depression: Effects on brain structure and treatment outcome

Narcís Cardoner, Virginia Soria, Mònica Gratacòs, Rosa Hernández-Ribas, Jesús Pujol, Marina Lõpez-Solà, Joan Deus, Mikel Urretavizcaya, Xavier P. Estivill, José M. Menchõn, Carles Soriano-Mas

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalDepression and Anxiety
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

Fingerprint

Brain-Derived Neurotrophic Factor
Major Depressive Disorder
Genotype
Depression
Brain
Homozygote
Hippocampus
Valine
Prefrontal Cortex
Methionine
Single Nucleotide Polymorphism
Inpatients
Magnetic Resonance Imaging
Technology
Phenotype
Gray Matter

Keywords

  • BDNF
  • brain morphometry
  • major depressive disorder
  • melancholic depression
  • neuroimaging
  • treatment outcome
  • Val66Met

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Cardoner, N., Soria, V., Gratacòs, M., Hernández-Ribas, R., Pujol, J., Lõpez-Solà, M., ... Soriano-Mas, C. (2013). Val66Met BDNF genotypes in melancholic depression: Effects on brain structure and treatment outcome. Depression and Anxiety, 30(3), 225-233. https://doi.org/10.1002/da.22025

Val66Met BDNF genotypes in melancholic depression : Effects on brain structure and treatment outcome. / Cardoner, Narcís; Soria, Virginia; Gratacòs, Mònica; Hernández-Ribas, Rosa; Pujol, Jesús; Lõpez-Solà, Marina; Deus, Joan; Urretavizcaya, Mikel; Estivill, Xavier P.; Menchõn, José M.; Soriano-Mas, Carles.

In: Depression and Anxiety, Vol. 30, No. 3, 03.2013, p. 225-233.

Research output: Contribution to journalArticle

Cardoner, N, Soria, V, Gratacòs, M, Hernández-Ribas, R, Pujol, J, Lõpez-Solà, M, Deus, J, Urretavizcaya, M, Estivill, XP, Menchõn, JM & Soriano-Mas, C 2013, 'Val66Met BDNF genotypes in melancholic depression: Effects on brain structure and treatment outcome', Depression and Anxiety, vol. 30, no. 3, pp. 225-233. https://doi.org/10.1002/da.22025
Cardoner N, Soria V, Gratacòs M, Hernández-Ribas R, Pujol J, Lõpez-Solà M et al. Val66Met BDNF genotypes in melancholic depression: Effects on brain structure and treatment outcome. Depression and Anxiety. 2013 Mar;30(3):225-233. https://doi.org/10.1002/da.22025
Cardoner, Narcís ; Soria, Virginia ; Gratacòs, Mònica ; Hernández-Ribas, Rosa ; Pujol, Jesús ; Lõpez-Solà, Marina ; Deus, Joan ; Urretavizcaya, Mikel ; Estivill, Xavier P. ; Menchõn, José M. ; Soriano-Mas, Carles. / Val66Met BDNF genotypes in melancholic depression : Effects on brain structure and treatment outcome. In: Depression and Anxiety. 2013 ; Vol. 30, No. 3. pp. 225-233.
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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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AU - Hernández-Ribas, Rosa

AU - Pujol, Jesús

AU - Lõpez-Solà, Marina

AU - Deus, Joan

AU - Urretavizcaya, Mikel

AU - Estivill, Xavier P.

AU - Menchõn, José M.

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N2 - 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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