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.
VAL66MET BDNF GENOTYPES IN MELANCHOLIC DEPRESSION: EFFECTS ON BRAIN STRUCTURE AND TREATMENT OUTCOME
Article first published online: 16 NOV 2012
© 2012 Wiley Periodicals, Inc.
Depression and Anxiety
Volume 30, Issue 3, pages 225–233, March 2013
How to Cite
Cardoner, N., Soria, V., Gratacòs, M., Hernández-Ribas, R., Pujol, J., López-Solà, M., Deus, J., Urretavizcaya, M., Estivill, X., Menchón, J. M. and Soriano-Mas, C. (2013), VAL66MET BDNF GENOTYPES IN MELANCHOLIC DEPRESSION: EFFECTS ON BRAIN STRUCTURE AND TREATMENT OUTCOME. Depress. Anxiety, 30: 225–233. doi: 10.1002/da.22025
- Issue published online: 6 MAR 2013
- Article first published online: 16 NOV 2012
- Manuscript Accepted: 18 OCT 2012
- Manuscript Revised: 7 OCT 2012
- Manuscript Received: 11 JUL 2012
- Psychiatry Genetics Network. Grant Number: G03/184
- Barcelona node of the Spanish National Genotyping Centre (CEGEN)
- Agència de Gestió d'Ajuts Universitaris i de Recerca. Grant Number: AGAUR 2009SGR1554
- Carlos III Health Institute. Grant Numbers: PI05/2307, PI09/01961, PI10/01753, CP10/00604
- CIBER. Grant Number: CB06/03/0034
- major depressive disorder;
- melancholic depression;
- brain morphometry;
- treatment outcome
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.
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).
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.
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.