Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Pharmacogenet Genomics. 2009 Nov;19(11):843-51. doi: 10.1097/FPC.0b013e3283313296.
Among serotonin (5-HT) receptors, the 5-HT3 receptor is the only ligand-gated ion channel. 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 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 in the response to haloperidol or risperidone. Seventy patients were treated for 4 weeks and positive symptoms, negative symptoms, and general psychopathology were measured by the Positive and Negative Syndrome Scale (PANSS).
HTR3E had an effect on the speed of response to antipsychotics. GG-allele carriers responded more quickly to treatment on the PANSS negative symptom subscale (P = 0.03) and on the total PANSS score (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 in response to antipsychotics. Solely, the HTR3E and also the HTR3A variant could exert a weak effect on the speed of response to antipsychotics.
在 5-羟色胺（5-HT）受体中，5-HT3 受体是唯一的配体门控离子通道。5-HT3 拮抗剂，如昂丹司琼和托吡酯，可能改善精神分裂症患者的听觉门控和神经认知缺陷。此外，许多抗精神病药物是 5-HT3 受体拮抗剂。然而，5-HT3 受体变体在精神分裂症患者对抗精神病药物反应中的作用仍不清楚。
在一项前瞻性、随机、双盲研究中，我们评估了亚基基因 HTR3A、HTR3B 的六个功能和编码变体，以及新型 HTR3C、HTR3D 和 HTR3E 亚基，以评估其对氟哌啶醇或利培酮的反应。70 例患者接受了 4 周的治疗，并通过阳性和阴性综合征量表（PANSS）评估阳性症状、阴性症状和一般精神病学。
HTR3E 对抗精神病药物的反应速度有影响。GG 等位基因携带者在 PANSS 阴性症状子量表（P=0.03）和总 PANSS 评分（P=0.04）上对治疗的反应更快，而与药物无关。在一项对 144 例接受非典型抗精神病药物治疗的精神分裂症患者的独立研究中，这一结果无法得到证实。
我们的发现表明，HTR3 变体对抗精神病药物反应的影响不大。只有 HTR3E 变体和 HTR3A 变体可能对抗精神病药物的反应速度产生微弱影响。
