Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain.
OBJECTIVE
The authors examined effects of a triallelic functional polymorphism of the human serotonin-transporter-linked promoter region (5-HTTLPR) on in vivo expression of serotonin transporter in the brain in healthy volunteers and subjects with major depressive disorder.


METHODS
Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin transporter binding potential (f(1)B(max)/K(d)) was determined by using positron emission tomography with the radiotracer [(11)C]McN 5652 and metabolite-corrected arterial input functions.


RESULTS
There was no difference in serotonin transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers.


CONCLUSIONS
Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood.
Parsey
Ramin V
RV
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. rparsey@neuron.cpmc.columbia.edu
Hastings
Ramin S
RS
Oquendo
Maria A
MA
Hu
Xianzhang
X
Goldman
David
D
Huang
Yung-yu
YY
Simpson
Norman
N
Arcement
Julie
J
Huang
Yiyun
Y
Ogden
R Todd
RT
Van Heertum
Ronald L
RL
Arango
Victoria
V
Mann
J John
JJ
D000328:Adult; D000367:Age Factors; D000483:Alleles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007546:Isoquinolines; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
D002250:Carbon Radioisotopes; D007546:Isoquinolines; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C058079:McN 5652