PMID- 24607934
OWN - NLM
STAT- MEDLINE
DCOM- 20150206
LR  - 20211021
IS  - 1095-9572 (Electronic)
IS  - 1053-8119 (Print)
IS  - 1053-8119 (Linking)
VI  - 94
DP  - 2014 Jul 1
TI  - Genetic variation in brain-derived neurotrophic factor val66met allele is 
      associated with altered serotonin-1A receptor binding in human brain.
PG  - 33-39
LID - S1053-8119(14)00136-0 [pii]
LID - 10.1016/j.neuroimage.2014.02.027 [doi]
AB  - Brain Derived Neurotrophic Factor (BDNF) regulates brain synaptic plasticity. 
      BDNF affects serotonin signaling, increases serotonin levels in brain tissue and 
      prevents degeneration of serotonin neurons. These effects have hardly been 
      studied in human brain. We examined the relationship of the functional val66met 
      polymorphism of the BDNF gene to serotonin 1A (5-HT(1A)) receptor binding in 
      vivo. 50 healthy volunteers (HV) and 50 acutely depressed, unmedicated patients 
      with major depressive disorder (MDD) underwent PET scanning with the 5-HT(1A) 
      receptor ligand, [(11)C]WAY-100635 and a metabolite corrected arterial input 
      function. A linear mixed effects model compared 5-HT(1A) receptor binding 
      potential (BP(F), proportional to the number of available receptors) in 13 brain 
      regions of interest between met allele carriers (met/met and val/met) and 
      noncarriers (val/val) using sex and C-1019G genotype of the 5-HT(1A) receptor 
      promoter functional polymorphism as covariates. There was an interaction between 
      diagnosis and allele (F=4.23, df=1, 94, p=0.042), such that met allele carriers 
      had 17.4% lower BP(F) than non-met carriers in the HV group (t=2.6, df=96, 
      p=0.010), but not in the MDD group (t=-0.4, df=96, p=0.58). These data are 
      consistent with a model where the met allele of the val66met polymorphism causes 
      less proliferation of serotonin synapses, and consequently fewer 5-HT(1A) 
      receptors. In MDD, however, the effect of the val66met polymorphism is not 
      detectable, possibly due to a ceiling effect of over-expression of 5-HT(1A) 
      receptors in mood disorders.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Lan, Martin J
AU  - Lan MJ
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA. Electronic address: 
      mal9151@nyp.org.
FAU - Ogden, R Todd
AU  - Ogden RT
AD  - Division of Molecular Imaging and Neuropathology, New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10021, USA; Department of 
      Biostatistics, Columbia University School of Public Health, 722 West 168th 
      Street, 6th Floor, New York, NY 10032, USA.
FAU - Huang, Yung-Yu
AU  - Huang YY
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA.
FAU - Oquendo, Maria A
AU  - Oquendo MA
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA.
FAU - Sullivan, Gregory M
AU  - Sullivan GM
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA.
FAU - Miller, Jeffrey
AU  - Miller J
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA.
FAU - Milak, Matthew
AU  - Milak M
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA.
FAU - Mann, J John
AU  - Mann JJ
AD  - Department of Psychiatry, Columbia University New York State Psychiatric 
      Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA; Division of 
      Molecular Imaging and Neuropathology, New York State Psychiatric Institute, 1051 
      Riverside Drive, Box 42, New York, NY 10021, USA; Department of Radiology, 
      Columbia University College of Physicians and Surgeons, 180 Fort Washington 
      Avenue, 3rd Floor, Harkness Pavilion, Room 313, New York, NY 10032, USA.
FAU - Parsey, Ramin V
AU  - Parsey RV
AD  - Department of Psychiatry and Behavioral Science, Department of Radiology, Stony 
      Brook Medicine, Health Sciences Center, T16, Rm-020, Stony Brook, NY 11794-8160, 
      USA.
LA  - eng
GR  - R01 MH074813/MH/NIMH NIH HHS/United States
GR  - T32 MH015144/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20140305
PL  - United States
TA  - Neuroimage
JT  - NeuroImage
JID - 9215515
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (desmethyl-WAY 100635)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Brain/*physiopathology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Depression/*genetics/metabolism
MH  - Depressive Disorder, Major/*genetics/*metabolism
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease/genetics
MH  - Genetic Variation/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperazines/pharmacokinetics
MH  - Polymorphism, Genetic/*genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Positron-Emission Tomography/methods
MH  - Protein Binding
MH  - Pyridines/pharmacokinetics
MH  - Radiopharmaceuticals/pharmacokinetics
MH  - Receptor, Serotonin, 5-HT1A/genetics/*metabolism
MH  - Statistics as Topic
MH  - Tissue Distribution
MH  - Young Adult
PMC - PMC4033823
MID - NIHMS573582
OTO - NOTNLM
OT  - BDNF
OT  - Brain
OT  - Depression
OT  - PET
OT  - Serotonin
OT  - [(11)C]WAY-100635
EDAT- 2014/03/13 06:00
MHDA- 2015/02/07 06:00
PMCR- 2015/07/01
CRDT- 2014/03/11 06:00
PHST- 2013/12/02 00:00 [received]
PHST- 2014/01/31 00:00 [revised]
PHST- 2014/02/24 00:00 [accepted]
PHST- 2014/03/11 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/02/07 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - S1053-8119(14)00136-0 [pii]
AID - 10.1016/j.neuroimage.2014.02.027 [doi]
PST - ppublish
SO  - Neuroimage. 2014 Jul 1;94:33-39. doi: 10.1016/j.neuroimage.2014.02.027. Epub 2014 
      Mar 5.