Association between serotonergic candidate genes and specific phenotypes of obsessive compulsive disorder.
BACKGROUND
The successful use of serotonin reuptake inhibitors (SRIs) in obsessive-compulsive disorder (OCD) has led to the hypothesis that serotonin plays a pivotal role in the pathogenesis of OCD. The purpose of the present study was to investigate the role of the serotonin transporter (5-HTT) and serotonin 5-HT1B and 5-HT2A receptor genes in OCD.


METHODS
The distribution of polymorphic variants was analyzed in 156 OCD cases and 134 control individuals by means of case-control association studies. Potential relevant OCD phenotypes founded on age of onset, positive family history for OCD, clinical subtypes, comorbidity and symptom severity were stratified according to 5-HTT, 5-HT1B and 5-HT2A genotypes.


RESULTS
Patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, taking in account OCD phenotypes, we found indication towards an association of the 5-HTTLPR S-allele with female OCD patients, and the 5-HT2A G-allele and GG genotype with patients with a positive family history of OCD and an early onset of disease.


CONCLUSIONS
Our data yields interesting preliminary results as regards the genetic underpinnings of OCD phenotypes that warrant further discussion and investigation.
Denys
Damiaan
D
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry University Medical Center Utrecht, Utrecht, The Netherlands. D.A.J.P.denys@azu.nl
Van Nieuwerburgh
Filip
F
Deforce
Dieter
D
Westenberg
Herman G M
HG
D000328:Adult; D000483:Alleles; D002872:Chromosome Deletion; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
D005819:Genetic Markers; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors