title: Exploring the impact of BDNF Val66Met genotype on serotonin transporter and serotonin-1A receptor binding.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kraus
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Pia
authors.initials: P
authors.lastname: Baldinger
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine Medical University of Vienna, Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Rami-Mark
authors.forename: Gregor
authors.initials: G
authors.lastname: Gryglewski
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gryglewsky
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg S
authors.initials: GS
authors.lastname: Kranz
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine Medical University of Vienna, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Haeusler
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.affiliation: Department of Psychiatry, Medical University of Halle, Halle, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000814:Aniline Compounds / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019208:Brain-Derived Neurotrophic Factor; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C579455:BDNF protein, human; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide