PMID- 22593075
OWN - NLM
STAT- MEDLINE
DCOM- 20120727
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 20
DP  - 2012 May 16
TI  - Brain-derived neurotrophic factor Val(6)(6)Met polymorphism affects resting regional 
      cerebral blood flow and functional connectivity differentially in women versus 
      men.
PG  - 7074-81
LID - 10.1523/JNEUROSCI.5375-11.2012 [doi]
AB  - The human Val(6)(6)Met single nucleotide polymorphism in the brain-derived 
      neurotrophic factor (BDNF) gene impacts BDNF signaling at the cellular level. At 
      the neural-systems level, it is associated with differences in prefrontal cortex 
      (PFC) and hippocampal function during performance of cognitive and affective 
      tasks. Because the impact of this variant on basal prefrontal and hippocampal 
      activity is not known but may be relevant to understanding the function of this 
      gene in health and disease, we studied 94 healthy individuals with H(2) (1)(5)O PET to 
      assess regional cerebral blood flow (rCBF) during rest and tested for 
      between-genotype differences. Because BDNF and gonadal steroid hormones 
      conjointly influence neuronal growth, survival, and plasticity in hippocampus and 
      PFC, we also tested for sex x genotype interactions. Finally, in light of the 
      known impact of BDNF on plasticity and dendritic arborization, we complimented 
      direct rCBF comparisons with connectivity analyses to determine how activity in 
      hippocampal and prefrontal regions showing between-genotype group differences 
      covaries with rCBF in other nodes throughout the brain in a genotype- or 
      sex-dependent manner. Compared with Val homozygotes, Met carriers had higher rCBF 
      in prefrontal (BA25 extending into BA10) and hippocampal/parahippocampal regions. 
      Moreover, there were significant sex x genotype interactions in regions 
      (including frontal, parahippocampal, and lateral temporal cortex) in which Val 
      homozygotes showed higher rCBF in females than males, but Met carriers showed the 
      opposite relationship. Functional connectivity analysis demonstrated that 
      correlations of BA25, hippocampus, and parahippocampus with frontal and temporal 
      networks were positive for Val homozygotes and negative for Met carriers. In 
      addition, sex x genotype analysis of functional connectivity revealed that 
      genotype affected directionality of the inter-regional correlations 
      differentially in men versus women. Our data indicate that BDNF allelic variation 
      and sex interactively affect basal prefrontal and hippocampal function.
FAU - Wei, Shau-Ming
AU  - Wei SM
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health 
      Intramural Research Programs, National Institutes of Health, Bethesda, Maryland 
      20892, USA.
FAU - Eisenberg, Daniel P
AU  - Eisenberg DP
FAU - Kohn, Philip D
AU  - Kohn PD
FAU - Kippenhan, Jonathan S
AU  - Kippenhan JS
FAU - Kolachana, Bhaskar S
AU  - Kolachana BS
FAU - Weinberger, Daniel R
AU  - Weinberger DR
FAU - Berman, Karen F
AU  - Berman KF
LA  - eng
GR  - ZIA MH002717-17/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Oxygen Radioisotopes)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Brain-Derived Neurotrophic Factor/genetics/*physiology
MH  - Cerebrovascular Circulation/genetics/*physiology
MH  - Female
MH  - Functional Neuroimaging/methods
MH  - Genotype
MH  - Hippocampus/diagnostic imaging/*physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neural Pathways/diagnostic imaging/physiology
MH  - Oxygen Radioisotopes
MH  - Polymorphism, Single Nucleotide
MH  - Positron-Emission Tomography/methods
MH  - Prefrontal Cortex/diagnostic imaging/*physiology
MH  - Sex Characteristics
MH  - Temporal Lobe/diagnostic imaging/physiology
PMC - PMC3362630
MID - NIHMS378299
EDAT- 2012/05/18 06:00
MHDA- 2012/07/28 06:00
PMCR- 2012/11/16
CRDT- 2012/05/18 06:00
PHST- 2012/05/18 06:00 [entrez]
PHST- 2012/05/18 06:00 [pubmed]
PHST- 2012/07/28 06:00 [medline]
PHST- 2012/11/16 00:00 [pmc-release]
AID - 32/20/7074 [pii]
AID - 3773036 [pii]
AID - 10.1523/JNEUROSCI.5375-11.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 May 16;32(20):7074-81. doi: 10.1523/JNEUROSCI.5375-11.2012.