Transmission disequilibrium analysis of the functional 5-HT3A receptor variant C178T in early-onset obsessive compulsive-disorder.
The 5-HT(3) receptor is unique among the serotonin receptors in that it is a ligand-gated ion channel. Dysfunction of the serotonin system is thought to contribute to the pathogenesis of obsessive-compulsive disorder (OCD). Apart from the standard treatment with serotonin reuptake inhibitors and behavioural therapy, a 5-HT(3) receptor antagonist has recently been shown to benefit some OCD patients, suggesting the 5-HT(3) receptor as a serotonergic candidate gene in the polygenic aetiology of OCD. A functional regulatory variant of the 5-HT(3A) receptor influences 5-HT(3) receptor expression, serotonin metabolites in cerebrospinal fluid, and amygdala reactivity. We therefore assessed whether this C178T variant influences the risk of developing OCD. In a family-based approach employing the transmission disequilibrium test, we analysed a unique sample of 75 children and adolescents with OCD, as well as their biological parents. We found no evidence for a preferential transmission of either allele to the patients--the estimated transmission rate for the C allele was 0.51 (95% CI 0.36-0.65). This argues against an involvement of the 5-HT(3A) receptor in the polygenic aetiology of early-onset OCD.
Mössner
Rainald
R
Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany. rainald.mossner@mail.uni-wurzberg.de
Döring
Nicole
N
Scherag
André
A
Schäfer
Helmut
H
Herpertz-Dahlmann
Beate
B
Remschmidt
Helmut
H
Schulz
Eberhard
E
Renner
Tobias
T
Wewetzer
Christoph
C
Warnke
Andreas
A
Lesch
Klaus-Peter
KP
Walitza
Susanne
S
D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D002648:Child; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000209:etiology / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics* / Q000502:physiology
D044406:Receptors, Serotonin, 5-HT3