5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option.
A role of the HTR3A-E genes in obsessive-compulsive disorder (OCD) can be expected based on promising effects of 5-HT3 receptor antagonists as adjunctive treatment of OCD. We therefore genotyped six common coding or promoter variants within the HTR3A-E genes in a case-control-sample consisting of N=236 OCD patients and N=310 control subjects and in N=58 parent-child-trios. Given the heterogeneous OCD phenotype, we also investigated OCD symptom dimensions and cognitive endophenotypes in subsamples. OCD patients scoring high for the washing subtype were significantly more likely to carry the c.256G-allele of the HTR3E variant rs7627615 (p=0.0001) as compared to OCD patients low for this symptom dimension. Visual organization was impaired in OCD patients and unaffected relatives as compared to healthy control subjects and carriers of the HTR3E c.256G/c.256G-genotype performed significantly worse (p=0.007). The case-control analyses revealed a nominal significant association of the HTR3D variant rs1000592 (p.H52R) with OCD (p=0.029) which was also evident after combination of the case-control and the trio-results (p=0.024). In male subjects, the variant rs6766410 (p.N163K) located in the HTR3C was significantly associated with OCD (p=0.007). The association findings of the HTR3C and the HTR3E remained significant after correction for the number of variants investigated. These findings indicate a role of common variants of the HTR3A-E genes in OCD and OCD-related phenotypes and further support the use of 5-HT3 receptor antagonists as novel treatment options. The HTR3E gene is a novel candidate gene impacting on the individual expression of OC symptoms and OCD-related cognitive dysfunction.
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany. Electronic address: leonard.lennertz@ukb.uni-bonn.de.
Leonhard
L
Lennertz
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Michael
M
Wagner
Department of Psychiatry and Psychotherapy, University of Greifswald, Greifswald, Germany.
Hans Jörgen
HJ
Grabe
Department of Psychiatry and Psychotherapy, University of Düsseldorf, Düsseldorf, Germany.
Petra E
PE
Franke
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Vera
V
Guttenthaler
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Friederike
F
Rampacher
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Svenja
S
Schulze-Rauschenbach
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Andrea
A
Vogeley
Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany.
Jens
J
Benninghoff
Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
Stephan
S
Ruhrmann
Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
Ralf
R
Pukrop
Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
Joachim
J
Klosterkötter
Department of Psychiatry and Psychotherapy, University of Munich, Munich, Germany.
Peter
P
Falkai
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Wolfgang
W
Maier
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, DE-53105 Bonn, Germany.
Rainald
R
Mössner
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D003192:Compulsive Behavior / Q000209:etiology*; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009771:Obsessive-Compulsive Disorder / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D014796:Visual Perception / Q000502:physiology*; D055815:Young Adult
D044406:Receptors, Serotonin, 5-HT3
5-HT3; Endophenotype; HTR3A; HTR3B; HTR3C; HTR3D; HTR3E; Obsessive-compulsive disorder; Serotonin; Symptom dimensions; Visual memory; Visual organization