5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option

Abstract

A role of the HTR3. A-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 HTR3. A-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 HTR3. E 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 HTR3. E c.256G/c.256G-genotype performed significantly worse (p=0.007). The case-control analyses revealed a nominal significant association of the HTR3. D 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 HTR3. C was significantly associated with OCD (p=0.007). The association findings of the HTR3. C and the HTR3. E remained significant after correction for the number of variants investigated. These findings indicate a role of common variants of the HTR3. A-E genes in OCD and OCD-related phenotypes and further support the use of 5-HT3 receptor antagonists as novel treatment options. The HTR3. E gene is a novel candidate gene impacting on the individual expression of OC symptoms and OCD-related cognitive dysfunction. © 2013 Elsevier B.V. and ECNP.