PMID- 23319002
OWN - NLM
STAT- MEDLINE
DCOM- 20140103
LR  - 20211021
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 18
IP  - 6
DP  - 2013 Jun
TI  - Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism differentially 
      predicts hippocampal function in medication-free patients with schizophrenia.
PG  - 713-20
LID - 10.1038/mp.2012.187 [doi]
AB  - A Val(66)Met single-nucleotide polymorphism (SNP) in the brain-derived 
      neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in 
      cultured hippocampal neurons and predicts impaired memory and exaggerated basal 
      hippocampal activity in healthy humans. Several clinical genetic association 
      studies along with multi-modal evidence for hippocampal dysfunction in 
      schizophrenia indirectly suggest a relationship between schizophrenia and 
      genetically determined BDNF function in the hippocampus. To directly test this 
      hypothesized relationship, we studied 47 medication-free patients with 
      schizophrenia or schizoaffective disorder and 74 healthy comparison individuals 
      with genotyping for the Val(66)Met SNP and [(15)O]H(2)O positron emission 
      tomography (PET) to measure resting and working memory-related hippocampal 
      regional cerebral blood flow (rCBF). In patients, harboring a Met allele was 
      associated with significantly less hippocampal rCBF. This finding was opposite to 
      the genotype effect seen in healthy participants, resulting in a significant 
      diagnosis-by-genotype interaction. Exploratory analyses of interregional resting 
      rCBF covariation revealed a specific and significant diagnosis-by-genotype 
      interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype 
      interaction was also found for working memory-related hippocampal rCBF change, 
      which was uniquely attenuated in Met allele-carrying patients. Thus, both 
      task-independent and task-dependent hippocampal neurophysiology accommodates a 
      Met allelic background differently in patients with schizophrenia than in control 
      subjects. Potentially consistent with the hypothesis that cellular sequelae of 
      the BDNF Val(66)Met SNP interface with aspects of schizophrenic hippocampal and 
      frontotemporal dysfunction, these results warrant future investigation to 
      understand the contributions of unique patient trait or state variables to these 
      robust interactions.
FAU - Eisenberg, D P
AU  - Eisenberg DP
AD  - Section on Integrative Neuroimaging, National Institute of Mental Health, NIH, 
      DHHS, Bethesda, MD 20892-1365, USA.
FAU - Ianni, A M
AU  - Ianni AM
FAU - Wei, S-M
AU  - Wei SM
FAU - Kohn, P D
AU  - Kohn PD
FAU - Kolachana, B
AU  - Kolachana B
FAU - Apud, J
AU  - Apud J
FAU - Weinberger, D R
AU  - Weinberger DR
FAU - Berman, K F
AU  - Berman KF
LA  - eng
GR  - T32 GM007198/GM/NIGMS NIH HHS/United States
GR  - ZIA MH002652-20/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20130115
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
RN  - J65BV539M3 (Deuterium Oxide)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Decision Support Techniques
MH  - Deuterium Oxide
MH  - Female
MH  - Genotype
MH  - Hippocampus/blood supply/diagnostic imaging/*physiopathology
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Memory, Short-Term/physiology
MH  - Methionine/genetics
MH  - Neuropsychological Tests
MH  - Oxygen/blood
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Positron-Emission Tomography
MH  - Rest/physiology
MH  - Schizophrenia/*genetics/*pathology
MH  - Valine/genetics
MH  - Young Adult
PMC - PMC3628926
MID - NIHMS414979
EDAT- 2013/01/16 06:00
MHDA- 2014/01/05 06:00
PMCR- 2013/12/01
CRDT- 2013/01/16 06:00
PHST- 2013/01/16 06:00 [entrez]
PHST- 2013/01/16 06:00 [pubmed]
PHST- 2014/01/05 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - mp2012187 [pii]
AID - 10.1038/mp.2012.187 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2013 Jun;18(6):713-20. doi: 10.1038/mp.2012.187. Epub 2013 Jan 
      15.