Influence of serotonin transporter gene polymorphism (5-HTTLPR polymorphism) on the relation between brain 5-HT transporter binding and heart rate corrected cardiac repolarization interval.
OBJECTIVE
Serotonin transporter gene polymorphism (5-HTTLPR polymorphism) predicts the degree of structural and functional connectivity in the brain, and less consistently the degree of vulnerability for anxiety and depressive disorders. It is less known how 5-HTTLPR polymorphism influences on the coupling between brain and neuronal cardiovascular control. The present study demonstrates the impact of 5-HTTLPR polymorphism on the relations between heart rate (HR) corrected cardiac repolarization interval (QTc interval) and the brain 5-HTT binding.


METHODS
Thirty healthy young adults (fifteen monozygotic twin pairs) (mean age 26±1.3 years, 16 females) were imagined with single-photon emission computed tomography (SPECT) using iodine-123 labeled 2β-carbomethoxy-3β-(4-iodophenyl) nortropane (nor-β-CIT). Continuous ECG recording was obtained from each participant at supine rest. Signal averaged QTc interval on continuous ECG was calculated and compared with the brain imaging results.


RESULTS
In the two groups [l homozygotes (n = 16, 10 females), s carriers (n = 14, 8 female)] HR and the length of QTc interval were not influenced by 5-HTTLPR polymorphism. There were no significant relations between HR and 5-HTT binding in the brain. There were significant associations between QTc interval and nor-β-CIT binding in the brain in l homozygotes, but not in s carriers (correlations for QTc interval and nor-β-CIT binding of striatum, thalamus and right temporal region were -0.8--0.9, (p<0.0005), respectively).


CONCLUSIONS
The finding of longer QTc interval with less 5-HTT binding availability in major serotonergic binding sites in l homozygotes, but not in s carriers, implicate to differentiated control of QTc interval by 5-HTTLPR polymorphism.
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland. ekauppil@gmail.com
Esa
E
Kauppila
Esko
E
Vanninen
Salla
S
Kaurijoki
Leila
L
Karhunen
Kirsi H
KH
Pietiläinen
Aila
A
Rissanen
Jari
J
Tiihonen
Ullamari
U
Pesonen
Jaakko
J
Kaprio
D000328:Adult; D001921:Brain / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011485:Protein Binding; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C086915:N-nor-3-(4'-iodophenyl)tropane-2-carboxylic acid methyl ester; D003042:Cocaine