PMID- 25220079
OWN - NLM
STAT- MEDLINE
DCOM- 20150819
LR  - 20211021
IS  - 1097-0193 (Electronic)
IS  - 1065-9471 (Print)
IS  - 1065-9471 (Linking)
VI  - 36
IP  - 1
DP  - 2015 Jan
TI  - BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain 
      serotonin levels.
PG  - 313-23
LID - 10.1002/hbm.22630 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in multiple aspects 
      of brain function including regulation of serotonin signaling. The BDNF val66met 
      polymorphism (rs6265) has been linked to aspects of serotonin signaling in humans 
      but its effects are not well understood. To address this, we evaluated whether 
      BDNF val66met was predictive of a putative marker of brain serotonin levels, 
      serotonin 4 receptor (5-HT4 ) binding assessed with [11C]SB207145 positron 
      emission tomography, which has also been associated with the 
      serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We 
      applied a linear latent variable model (LVM) using regional 5-HT4 binding values 
      (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, 
      allowing us to explicitly model brain-wide and region-specific genotype effects 
      on 5-HT4 binding. Our data supported an LVM wherein BDNF val66met significantly 
      predicted a LV reflecting [11C]SB207145 binding across regions (P = 0.005). BDNF 
      val66met met-carriers showed 2-9% higher binding relative to val/val homozygotes. 
      In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower 
      neocortical binding relative to LL homozygotes (P = 7.3 x 10(-6)). We observed no 
      evidence for genetic interaction. Our findings indicate that BDNF val66met 
      significantly predicts a common regulator of brain [11C]SB207145 binding, which 
      we hypothesize reflects brain serotonin levels. In contrast, our data indicate 
      that 5-HTTLPR specifically affects 5-HT4 binding in the neocortex. These findings 
      implicate serotonin signaling as an important molecular mediator underlying the 
      effects of BDNF val66met and 5-HTTLPR on behavior and related risk for 
      neuropsychiatric illness in humans.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Fisher, Patrick M
AU  - Fisher PM
AD  - Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital 
      Rigshospitalet, Copenhagen O, Denmark; Neurobiology Research Unit, Copenhagen 
      University Hospital Rigshospitalet, Copenhagen O, Denmark.
FAU - Holst, Klaus K
AU  - Holst KK
FAU - Adamsen, Dea
AU  - Adamsen D
FAU - Klein, Anders Bue
AU  - Klein AB
FAU - Frokjaer, Vibe G
AU  - Frokjaer VG
FAU - Jensen, Peter S
AU  - Jensen PS
FAU - Svarer, Claus
AU  - Svarer C
FAU - Gillings, Nic
AU  - Gillings N
FAU - Baare, William F C
AU  - Baare WF
FAU - Mikkelsen, Jens D
AU  - Mikkelsen JD
FAU - Knudsen, Gitte M
AU  - Knudsen GM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140913
PL  - United States
TA  - Hum Brain Mapp
JT  - Human brain mapping
JID - 9419065
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Piperidines)
RN  - 0 (SB 207145)
RN  - 0 (SLC6A4 protein, human)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brain/diagnostic imaging/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Imaging, Three-Dimensional
MH  - Linear Models
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Methionine/genetics
MH  - Middle Aged
MH  - Piperidines/metabolism
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Protein Binding/drug effects
MH  - Radionuclide Imaging
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/*genetics
MH  - Valine/genetics
MH  - Young Adult
PMC - PMC6869129
OTO - NOTNLM
OT  - 5-HT4 receptor
OT  - 5-HTTLPR
OT  - BDNF
OT  - positron emission tomography
OT  - serotonin
EDAT- 2014/09/16 06:00
MHDA- 2015/08/20 06:00
PMCR- 2014/09/13
CRDT- 2014/09/16 06:00
PHST- 2014/05/07 00:00 [received]
PHST- 2014/07/29 00:00 [revised]
PHST- 2014/08/29 00:00 [accepted]
PHST- 2014/09/16 06:00 [entrez]
PHST- 2014/09/16 06:00 [pubmed]
PHST- 2015/08/20 06:00 [medline]
PHST- 2014/09/13 00:00 [pmc-release]
AID - HBM22630 [pii]
AID - 10.1002/hbm.22630 [doi]
PST - ppublish
SO  - Hum Brain Mapp. 2015 Jan;36(1):313-23. doi: 10.1002/hbm.22630. Epub 2014 Sep 13.