PMID- 22585743
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20200930
IS  - 1552-485X (Electronic)
IS  - 1552-4841 (Linking)
VI  - 159B
IP  - 5
DP  - 2012 Jul
TI  - Reduced fractional anisotropy in the uncinate fasciculus in patients with major 
      depression carrying the met-allele of the Val66Met brain-derived neurotrophic 
      factor genotype.
PG  - 537-48
LID - 10.1002/ajmg.b.32060 [doi]
AB  - Experimental studies support a neurotrophic hypothesis of major depressive 
      disorder (MDD). The aim of this study was to determine the effect of Val66Met 
      brain-derived neurotrophic factor (BDNF) polymorphism on the white matter fiber 
      tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample 
      of patients with MDD and healthy controls. Thirty-seven patients with MDD and 42 
      healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 
      diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic 
      tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was 
      genotyped. Fiber tracts connecting the hippocampus and amygdala with the 
      prefrontal lobe, namely uncinate fasciculus (UF), fornix, and cingulum were 
      analyzed. A significant interaction was found in the UF between BDNF alleles and 
      diagnosis. Patients carrying the BDNF met-allele had smaller fractional 
      anisotropy (FA) in the UF compared to those patients homozygous for val-allele 
      and compared to healthy subjects carrying the met-allele. A significant three-way 
      interaction was detected between region of the cingulum (dorsal, rostral, and 
      parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was 
      detectable in the left rostral cingulum for met-allele carriers when compared to 
      val/val alelle carriers. We provide evidence for the importance of the 
      neurotrophic involvement in limbic and prefrontal connections. The met-allele of 
      the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions 
      associated with the UF, a tract known to be related to negative 
      emotional-cognitive processing bias, declarative memory problems, and autonoetic 
      self awareness.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Carballedo, A
AU  - Carballedo A
AD  - Department of Psychiatry, Institute of Neuroscience, University of Dublin, 
      Trinity College Dublin, Dublin, Ireland.
FAU - Amico, F
AU  - Amico F
FAU - Ugwu, I
AU  - Ugwu I
FAU - Fagan, A J
AU  - Fagan AJ
FAU - Fahey, C
AU  - Fahey C
FAU - Morris, D
AU  - Morris D
FAU - Meaney, J F
AU  - Meaney JF
FAU - Leemans, A
AU  - Leemans A
FAU - Frodl, T
AU  - Frodl T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120514
PL  - United States
TA  - Am J Med Genet B Neuropsychiatr Genet
JT  - American journal of medical genetics. Part B, Neuropsychiatric genetics : the 
      official publication of the International Society of Psychiatric Genetics
JID - 101235742
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - *Alleles
MH  - Anisotropy
MH  - Brain/*pathology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Case-Control Studies
MH  - Demography
MH  - Depressive Disorder, Major/drug therapy/*genetics/*pathology
MH  - Diffusion Tensor Imaging
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Young Adult
EDAT- 2012/05/16 06:00
MHDA- 2012/10/12 06:00
CRDT- 2012/05/16 06:00
PHST- 2012/01/12 00:00 [received]
PHST- 2012/04/18 00:00 [accepted]
PHST- 2012/05/16 06:00 [entrez]
PHST- 2012/05/16 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
AID - 10.1002/ajmg.b.32060 [doi]
PST - ppublish
SO  - Am J Med Genet B Neuropsychiatr Genet. 2012 Jul;159B(5):537-48. doi: 
      10.1002/ajmg.b.32060. Epub 2012 May 14.