Yoshimura Reiji, Hori Hikaru, Sugita Atsuko, Ueda Nobuhisa, Kakihara Shingo, Umene Wakako, Nakano Yuichiro, Shinkai Koji, Mitoma Masae, Ohta Makiko, Shinkai Takahiro, Nakamura Jun
Department of Psychiatry, University of Occupational and Environmental Health 1-1Iseigaoka, Yahatanishiku, Kitakyushu, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jun 30;31(5):1072-7. doi: 10.1016/j.pnpbp.2007.03.010. Epub 2007 Mar 24.
In the present study, we investigated the effects of risperidone treatment for 4 weeks on plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain-derived neurotrophic factor (BDNF) in 89 schizophrenic patients. We also compared the plasma levels of BDNF and MHPG between the schizophrenic group and 103 sex-and age-matched normal controls. In addition, we investigated the effects of two SNPs of the noradrenaline transporter (NAT) gene on plasma levels of MHPG, BDNF, and clinical improvement. The mean dose of risperidone was 3.8+/-1.4 mg/day. We demonstrated that treatment with risperidone increased plasma MHPG levels, and this increase was associated with an improvement of the negative symptoms of schizophrenia. In contrast, plasma BDNF did not change after 4 weeks of risperidone treatment, and the two SNPs in NAT did not influence the response to risperidone treatment or plasma MHPG and BDNF levels. These results suggest that the enhancement of noradrenergic neurons by risperidone, which occurs independently of the two SNPs of NAT, plays a role in the clinical efficacy of the drug.
在本研究中，我们调查了89例精神分裂症患者接受利培酮治疗4周对其血浆3-甲氧基-4-羟基苯乙二醇（MHPG）水平及脑源性神经营养因子（BDNF）的影响。我们还比较了精神分裂症组与103名年龄和性别匹配的正常对照者之间BDNF和MHPG的血浆水平。此外，我们研究了去甲肾上腺素转运体（NAT）基因的两个单核苷酸多态性（SNP）对MHPG和BDNF血浆水平及临床改善情况的影响。利培酮的平均剂量为3.8±1.4毫克/天。我们证明，利培酮治疗可提高血浆MHPG水平，且这种升高与精神分裂症阴性症状的改善相关。相比之下，利培酮治疗4周后血浆BDNF未发生变化，NAT基因的两个SNP也未影响对利培酮治疗的反应或血浆MHPG和BDNF水平。这些结果表明，利培酮对去甲肾上腺素能神经元的增强作用独立于NAT基因的两个SNP，在该药物的临床疗效中发挥作用。
