Polymorphic variations in the 5-HTT promoter region and 5 HTT binding in the human brain: A positron emission tomography study with [11C] DASB

Abstract

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Objectives: Studies in vitro suggest 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, evidence for this effect in vivo is inconsistent in human studies. The reasons for this inconsistency may be smaller subject numbers or use of sub-optimal radiotracer. We tested this in a larger sample of healthy volunteers with a selective 5-HTT radiotracer.

Methods: We used Positron Emission Tomography (PET) in conjunction with the selective 5-HTT ligand [11C] DASB to examine the availability of the 5-HTT in seven brain regions (putamen, dorsal raphe, caudate, thalamus, amygdala, hippocampus and anterior cingulate) in 63 healthy volunteers who were genotyped for short (S) and long (L) variants (SLC6A4 & rs25531) of the 5-HTTLPR.

Results: [11C] DASB binding potential was not influenced by allelic status of participants whether classified on a biallelic (F=0.61, df 2,59, p=0.55) or triallelic basis (F=0.09, df 2,59, p=0.91) in any of the seven regions tested.

Conclusions: Our PET findings, in a large cohort with a near optimal radiotracer, suggest 5-HTTLPR polymorphic variations do not affect the expression of the 5-HTT in adult human brain. The reported impact of 5-HTTLPR polymorphic variations on emotional processing and vulnerability to depression are more likely therefore to be expressed through effects during neurodevelopment.

Research Support: Funded in part by Medical Research Coucil & GSK.