Neuropsychiatric Research Institute, School of Medicine, Southeast University, Nanjing, China.
Pharmacogenomics. 2011 Aug;12(8):1127-36. doi: 10.2217/pgs.11.46. Epub 2011 Jul 12.
Sexual dysfunction induced by antipsychotic drug treatment is under investigated and under reported. This study aimed to determine the influence of genetic polymorphisms in the D2 dopamine receptor (DRD2) and endothelial nitric oxide synthase (eNOS) genes, and the possible role of blood prolactin concentrations on sexual function in schizophrenic patients.
MATERIALS & METHODS: Male remitted schizophrenic patients (n = 100), who were living with a sexual partner and receiving antipsychotic drug monotherapy for at least 6 months, were assessed for sexual and erectile dysfunction using the Arizona Sexual Experience Scale and the five-item version of the International Index of Erectile Function. Blood samples were taken for plasma prolactin determination and genotyped for four polymorphisms: DRD2 (-141C Ins/Del and Taq1A) and eNOS gene (G894T and T-786C).
The -141C Ins/Del, but not Taq1A, polymorphism of the DRD2 gene was significantly associated with sexual dysfunction with the del allele being less frequent in sexual dysfunction subjects. Neither of the eNOS polymorphisms, G894T or T-786C, was significantly associated with sexual or erectile dysfunction. Prolactin concentrations were significantly higher in patients with erectile dysfunction but did not reach significance in those with sexual dysfunction. Prolactin was also reduced in -141C Del allele carriers. The frequency and severity of sexual dysfunction in the patients receiving typical antipsychotics was significantly greater than those receiving risperidone or clozapine, while prolactin concentrations were significantly higher in subjects receiving risperidone compared with those receiving clozapine or typical antipsychotics.
This is the first evidence indicating that antipsychotic drug treatment in men is associated with a variant in the DRD2 gene in which the -141C Del allele might be a protective factor. While this may, in part, be mediated by effects on prolactin, other factors are likely to contribute to the greater sexual dysfunction in patients receiving typical antipsychotics.
抗精神病药物治疗引起的性功能障碍研究不足且报道较少。本研究旨在确定多巴胺 D2 受体（DRD2）和内皮型一氧化氮合酶（eNOS）基因的遗传多态性，以及血液催乳素浓度对精神分裂症患者性功能的影响。
100 名缓解期男性精神分裂症患者，他们与性伴侣生活在一起，并接受抗精神病药物单一疗法至少 6 个月，使用亚利桑那性体验量表和国际勃起功能指数的 5 项版本评估性功能和勃起功能障碍。采集血样测定血浆催乳素浓度，并对 4 种多态性进行基因分型：DRD2（-141CIns/Del 和 Taq1A）和 eNOS 基因（G894T 和 T-786C）。
DRD2 基因的-141CIns/Del 多态性而非 Taq1A 多态性与性功能障碍显著相关，del 等位基因在性功能障碍患者中较少见。eNOS 基因的两种多态性 G894T 和 T-786C 均与性功能或勃起功能障碍无显著相关性。勃起功能障碍患者的催乳素浓度显著升高，但在性功能障碍患者中未达到显著水平。-141C Del 等位基因携带者的催乳素也减少。接受典型抗精神病药物治疗的患者的性功能障碍频率和严重程度显著高于接受利培酮或氯氮平治疗的患者，而接受利培酮治疗的患者的催乳素浓度显著高于接受氯氮平或典型抗精神病药物治疗的患者。
这是首次表明男性抗精神病药物治疗与 DRD2 基因的变异有关，其中-141C Del 等位基因可能是一种保护因素。虽然这可能部分是通过对催乳素的影响介导的，但其他因素可能导致接受典型抗精神病药物治疗的患者性功能障碍更大。
