No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism

Background: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [123I]-2-β-carbomethoxy-3-β-(4-iodophenyl)tropane ([123I]-β-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. Methods: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus–hypothalamus and mesencephalon–pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [123I]-β-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. Results: Specific binding ratios in the thalamus–hypothalamus were 2.65 ± 0.4 in subjects with the l/l genotype (n = 3), 2.76 ± 0.5 in subjects with the l/s genotype (n = 9), and 2.77 ± 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon–pons were 1.43 ± 0.3 (l/l; n = 3), 1.37 ± 0.3 (l/s; n = 9), and 1.28 ± 0.3 (s/s; n = 4). None of these differences was statistically significant. Conclusions: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus–hypothalamus and mesencephalon–pons of healthy subjects.