title: Genetic variation in brain-derived neurotrophic factor is associated with serotonin transporter but not serotonin-1A receptor availability in men.
abstract: BACKGROUND
  The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF).
  
  
  METHODS
  Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [(11)C]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [(11)C]WAY-100635.
  
  
  RESULTS
  Several single nucleotide polymorphisms were associated with [(11)C]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [(11)C]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with (123)I-beta-CIT as ligand.
  
  
  CONCLUSIONS
  Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, Gothenburg University, Gothenburg, Sweden. susanne.henningsson@pharm.gu.se
authors.forename: Susanne
authors.initials: S
authors.lastname: Henningsson
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Borg
authors.forename: Johan
authors.initials: J
authors.lastname: Lundberg
authors.forename: Jessica
authors.initials: J
authors.lastname: Bah
authors.forename: Mats
authors.initials: M
authors.lastname: Lindström
authors.forename: Erik
authors.initials: E
authors.lastname: Ryding
authors.forename: Hristina
authors.initials: H
authors.lastname: Jovanovic
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Saijo
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Ingmar
authors.initials: I
authors.lastname: Rosén
authors.forename: Lil
authors.initials: L
authors.lastname: Träskman-Bendz
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011869:Radioligand Assay / Q000379:methods; D011877:Radionuclide Imaging; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D012727:Sex Characteristics; D013406:Suicide, Attempted
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A