Abstract

Among serotonin (5-HT) receptors, the 5-HT3 receptors are the only ion channels. 5-HT3 antagonists such as ondansetron and tropisetron may improve auditory gating and neurocognitive deficits in schizophrenic patients. Moreover, many antipsychotic drugs are antagonists at 5-HT3 receptors. However, the role of 5-HT3 receptor variants on the response to antipsychotic drugs in schizophrenic patients is still unclear. In a prospective, randomized, double-blind study we have assessed six functional and coding variants of the subunit genes HTR3A, HTR3B as well as the novel HTR3C, HTR3D and HTR3E subunits on the response to haloperidol or risperidone. 70 patients were treated for four weeks and positive symptoms, negative symptoms and general psychopathology measured by PANSS. HTR3E had an effect on the response speed to antipsychotics. GG allele carriers responded more quickly to treatment on PANSS negative symptom subscale (p=0.03) and on the total PANSS scale (p=0.04) irrespective of medication. In a second independent study of 144 schizophrenia patients treated with atypical antipsychotics, this effect could not be confirmed. Our findings argue against a major effect of HTR3 variants on the response to antipsychotics. Solely the HTR3E and also the HTR3A variant could exert a weak effect on the speed of response to antipsychotics.