title: Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain.
abstract: Studies in vitro suggest that the expression of the serotonin transporter (5-HTT) is regulated by polymorphic variation in the promoter region of the 5-HTT gene (5-HTTLPR); however, results from human brain imaging studies examining the relation between 5-HTT genotype and 5-HTT radioligand binding in vivo have been inconsistent. This inconsistency could reflect small participant numbers or the use of sub-optimal radiotracer for measuring the 5-HTT. We used positron emission tomography in conjunction with the selective 5-HTT ligand [(11)C] DASB to examine the availability of the 5-HTT in seven brain regions in 63 healthy European caucasian volunteers who were genotyped for short (S) and long (L) variants (SLC6A4 and rs25531) of the 5-HTTLPR. [(11)C] DASB binding potential was not influenced by the allelic status of participants whether classified on a biallelic or triallelic basis in any of the regions studied. Our PET findings, in a relatively large sample with a near optimal radiotracer, suggest that 5-HTTLPR polymorphic variation does not affect the availability of 5-HTT to [(11)C] DASB binding in adult human brain. The reported impact of 5-HTTLPR polymorphic variation on emotional processing and vulnerability to depression are more likely therefore to be expressed through effects exerted during neurodevelopment.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK.
authors.forename: N V
authors.initials: NV
authors.lastname: Murthy
authors.forename: S
authors.initials: S
authors.lastname: Selvaraj
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: Z
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: W J
authors.initials: WJ
authors.lastname: Riedel
authors.forename: P
authors.initials: P
authors.lastname: Peers
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: B J
authors.initials: BJ
authors.lastname: Sahakian
authors.forename: M A
authors.initials: MA
authors.lastname: Laruelle
authors.forename: E A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: P M
authors.initials: PM
authors.lastname: Grasby
mesh_terms: D000328:Adult; D000483:Alleles; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D003430:Cross-Sectional Studies; D005060:Europe; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D044465:White People / Q000235:genetics
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins