Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype

Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an AG exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [(11)C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin.We assessed 5-HTT binding potential (BP (2)) in the midbrain of 19 healthy subjects with positron emission tomography and [(11)C]DASB. Accounting for the hypothesized functional similarity of L (G) and S in driving 5-HTT transcription, we assessed whether L (A) L (A) homozygotes display increased midbrain BP (2) compared with carriers of at least one S allele.BP (2) in the midbrain was significantly increased in L (A) L (A) homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected.This in vivo study provides further evidence that subjects homozygous for the L (A) allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections.