RT Journal Article
SR Electronic
T1 Polymorphic variations in the 5-HTT promoter region and 5 HTT binding in the human brain: A positron emission tomography study with [11C] DASB
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 131P
OP 131P
VO 49
IS supplement 1
A1 Murthy, Venkatesha
A1 Cowen, Philip
A1 Selvaraj, Sudhakar
A1 Riedel, Wim
A1 Peers, Polly
A1 Kennedy, James
A1 Laruelle, Marc
A1 Rabiner, Eugenii
A1 Grasby, Paul
YR 2008
UL http://jnm.snmjournals.org/content/49/supplement_1/131P.2.abstract
AB 521 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.