PMID- 25188405
OWN - NLM
STAT- MEDLINE
DCOM- 20151207
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - Exploring the impact of BDNF Val66Met genotype on serotonin transporter and 
      serotonin-1A receptor binding.
PG  - e106810
LID - 10.1371/journal.pone.0106810 [doi]
LID - e106810
AB  - BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism 
      (rs6265) may impact on the in-vivo binding of important serotonergic structures 
      such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. 
      Previous positron emission tomography (PET) studies on the association between 
      Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated 
      equivocal results. METHODS: We conducted an imaging genetics study investigating 
      the effect of Val66Met genotype on 5-HTT or 5-HT1A BPND in 92 subjects. Forty-one 
      subjects (25 healthy subjects and 16 depressive patients) underwent genotyping 
      for Val66Met and PET imaging with the 5-HTT specific radioligand [11C]DASB. 
      Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT1A binding with 
      the radioligand [carbonyl-11C]WAY-100635 were ascertained. Voxel-wise and region 
      of interest-based analyses of variance were used to examine the influence of 
      Val66Met on 5-HTT and 5-HT1A BPND. RESULTS: No significant differences of 5-HTT 
      nor 5-HT1A BPND between BDNF Val66Met genotype groups (val/val vs. met-carrier) 
      were detected. There was no interaction between depression and Val66Met genotype 
      status. CONCLUSION: In line with previous data, our work confirms an absent 
      effect of BDNF Val66Met on two major serotonergic structures. These results could 
      suggest that altered protein expression associated with genetic variants, might 
      be compensated in vivo by several levels of unknown feedback mechanisms. In 
      conclusion, Val66Met genotype status is not associated with changes of in-vivo 
      binding of 5-HTT and 5-HT1A receptors in human subjects.
FAU - Kraus, Christoph
AU  - Kraus C
AD  - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, 
      Austria.
FAU - Baldinger, Pia
AU  - Baldinger P
AD  - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, 
      Austria.
FAU - Rami-Mark, Christina
AU  - Rami-Mark C
AD  - Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear 
      Medicine Medical University of Vienna, Vienna, Austria.
FAU - Gryglewski, Gregor
AU  - Gryglewski G
FAU - Kranz, Georg S
AU  - Kranz GS
AD  - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, 
      Austria.
FAU - Haeusler, Daniela
AU  - Haeusler D
AD  - Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear 
      Medicine Medical University of Vienna, Vienna, Austria.
FAU - Hahn, Andreas
AU  - Hahn A
AD  - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, 
      Austria.
FAU - Wadsak, Wolfgang
AU  - Wadsak W
AD  - Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear 
      Medicine Medical University of Vienna, Vienna, Austria.
FAU - Mitterhauser, Markus
AU  - Mitterhauser M
AD  - Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear 
      Medicine Medical University of Vienna, Vienna, Austria.
FAU - Rujescu, Dan
AU  - Rujescu D
AD  - Department of Psychiatry, Medical University of Halle, Halle, Germany.
FAU - Kasper, Siegfried
AU  - Kasper S
AD  - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, 
      Austria.
FAU - Lanzenberger, Rupert
AU  - Lanzenberger R
AD  - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, 
      Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140904
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile)
RN  - 0 (Aniline Compounds)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Sulfides)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 333DO1RDJY (Serotonin)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
SB  - IM
EIN - PLoS One. 2014;9(11):e113173. Gryglewsky, Gregor [corrected to Gryglewski, 
      Gregor]
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Substitution
MH  - Aniline Compounds/pharmacology
MH  - Brain/diagnostic imaging/drug effects/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Case-Control Studies
MH  - Depressive Disorder/diagnostic imaging/*genetics/metabolism/pathology
MH  - Female
MH  - Gene Expression
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperazines/pharmacology
MH  - *Polymorphism, Single Nucleotide
MH  - Positron-Emission Tomography
MH  - Protein Binding
MH  - Pyridines/pharmacology
MH  - Radiopharmaceuticals/pharmacology
MH  - Receptor, Serotonin, 5-HT1A/*genetics/metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*genetics/metabolism
MH  - Sulfides/pharmacology
PMC - PMC4154779
COIS- Competing Interests: Without any relevance to this work, S. Kasper declares that 
      he has received grant/research support from Eli Lilly, Lundbeck A/S, 
      Bristol-Myers Squibb, Servier, Sepracor, GlaxoSmithKline, Organon, and has served 
      as a consultant or on advisory boards for AstraZeneca, Austrian Sick Found, 
      Bristol-Myers Squibb, GlaxoSmithKline, Eli Lily, Lundbeck A/S, Pfizer, Organon, 
      Sepracor, Janssen, and Novartis, and has served on speakers' bureaus for 
      AstraZeneca, Eli Lilly, Lundbeck A/S, Servier, Sepracor and Janssen. R. 
      Lanzenberger has received travel grants and conference speaker honoraria from 
      AstraZeneca, Lundbeck A/S and Roche Austria GmbH. C. Kraus and P. Baldinger have 
      received travel grants and conference speaker honoraria from Roche. G.S. Kranz 
      received travel grants from Roche and AOP Orphan. W. Wadsak has received research 
      support from Rotem GmbH, ABX, Iason, Advion and Raytest Austria and has served as 
      a consultant/trainer for Bayer and THP. The authors M. Mitterhauser, C. 
      Rami-Mark, and A. Hahn report no financial relationships with commercial 
      interests.
EDAT- 2014/09/05 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/09/04
CRDT- 2014/09/05 06:00
PHST- 2014/04/16 00:00 [received]
PHST- 2014/07/28 00:00 [accepted]
PHST- 2014/09/05 06:00 [entrez]
PHST- 2014/09/05 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/09/04 00:00 [pmc-release]
AID - PONE-D-14-17228 [pii]
AID - 10.1371/journal.pone.0106810 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 4;9(9):e106810. doi: 10.1371/journal.pone.0106810. eCollection 
      2014.