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.