title: BDNF Val66Met polymorphism in patterns of neural activation in individuals with MDD and healthy controls.
abstract: BACKGROUND
  Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependant (BOLD) signal between individuals with MDD and healthy controls for both allelic variants.
  
  
  METHODS
  Individuals with MDD (N = 37) and healthy controls (N = 39) were genotyped for rs6265 and compared separately in each allelic variant for BOLD response in a functional magnetic resonance imaging experiment examining appraisal of emotional scenes. The two allelic variants were also compared separately for both individuals with MDD and healthy controls.
  
  
  RESULTS
  In the homozygous valine group MDD was associated with decreased neural activation in areas responsible for cognitive appraisal of emotional scenes. In the methionine group MDD was related to increased activation in subcortical regions responsible for visceral reaction to emotional stimuli. During an MDD episode methionine carriers showed more activation in areas associated with cognitive appraisal of emotional information in comparison to valine homozygotes.
  
  
  CONCLUSIONS
  Small sample size of healthy controls carrying methionine (N=8).
  
  
  CONCLUSIONS
  Our results suggest that allelic variations in the rs6265 gene lead to specific neural correlates of MDD which may be associated with different mechanisms of MDD in the two allelic groups. This may have potential importance for screening and treatment of patients.
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK; Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, UK. Electronic address: dml45@cam.ac.uk.
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Lisiecka
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Erik
authors.initials: E
authors.lastname: O'Hanlon
authors.affiliation: Centre for Advanced Medical Imaging (CAMI), St James's Hospital, Dublin, Ireland; Department of Clinical Medicine, Trinity College Dublin, Ireland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fagan
authors.affiliation: Department of Psychiatry, Trinity College Dublin, Ireland.
authors.forename: Angela
authors.initials: A
authors.lastname: Carballedo
authors.affiliation: Cognitive Genetics and Therapy Group, Discipline of Biochemistry and School of Psychology, National University of Ireland, Galway, Ireland.
authors.forename: Derek
authors.initials: D
authors.lastname: Morris
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK; Behavioural and Clinical Neuroscience Institute, Department of Psychiatry, University of Cambridge, UK; Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, Trinity College Dublin, Ireland; Department of Psychiatry, University of Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D004644:Emotions / Q000502:physiology; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Brain-derived neurotrophic factor; Emotional response; Functional magnetic resonance imaging; Major depressive disorder; Prefrontal cortex; Striatum