title: Val66Met BDNF genotypes in melancholic depression: effects on brain structure and treatment outcome.
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.
authors.affiliation: Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Feixa Llarga s/n, Barcelona, Spain. ncardoner@bellvitgehospital.cat
authors.forename: Narcís
authors.initials: N
authors.lastname: Cardoner
authors.forename: Virginia
authors.initials: V
authors.lastname: Soria
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Rosa
authors.initials: R
authors.lastname: Hernández-Ribas
authors.forename: Jesús
authors.initials: J
authors.lastname: Pujol
authors.forename: Marina
authors.initials: M
authors.lastname: López-Solà
authors.forename: Joan
authors.initials: J
authors.lastname: Deus
authors.forename: Mikel
authors.initials: M
authors.lastname: Urretavizcaya
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: José M
authors.initials: JM
authors.lastname: Menchón
authors.forename: Carles
authors.initials: C
authors.lastname: Soriano-Mas
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology*; D003865:Major Depressive Disorder / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000295:instrumentation / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016896:Treatment Outcome; D014633:Valine / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine