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急性精神分裂症患者中缬氨酸108/158甲硫氨酸多态性与阿立哌唑治疗反应

Val 108/158 Met polymorphism and treatment response to aripiprazole in patients with acute schizophrenia.

作者信息

Kaneko Haruka, Miura Itaru, Kanno-Nozaki Keiko, Horikoshi Sho, Hino Mizuki, Yabe Hirooki

机构信息

Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.

Department of Neuropsychiatry, Hoshi General Hospital, Fukushima, Japan.

出版信息

Neuropsychiatr Dis Treat. 2018 Jun 22;14:1657-1663. doi: 10.2147/NDT.S164647. eCollection 2018.

Abstract

INTRODUCTION

The Val 108/158 Met polymorphism (rs4680) may affect treatment response to antipsychotics, as well as metabolism and dynamics of neurotransmitters during the treatment of schizophrenia. We investigated the effects of the Val 108/158 Met polymorphism on treatment response to aripiprazole and plasma monoamine metabolite levels in patients with acute schizophrenia.

MATERIALS AND METHODS

Forty patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured Positive and Negative Syndrome Scale (PANSS) and plasma levels of homovanillic acid (HVA) and plasma MHPG (3-methoxy-4-hydroxyphenethyleneglycol) at baseline and endpoint. The Val 108/158 Met polymorphism was genotyped with the polymerase chain reaction and restriction fragment length polymorphism.

RESULTS

There were significant genotype-time interactions on PANSS total and general psychopathology scores, with Met/Met genotype showing greater improvement. The response rate to aripiprazole did not differ between Val 108/158 Met genotype groups. We found a significant time effect on plasma MHPG levels, but no time effect on plasma HVA levels or time-genotype interactions in the plasma levels of HVA and MHPG. Although the responder rate did not differ among the 3 genotype groups.

CONCLUSION

Our results suggest that individuals with the Met/Met genotype had greater improvement in PANSS score after the treatment with aripiprazole. On the other hand, the Val 108/158 Met polymorphism may not induce changes in plasma levels of monoamine metabolites during aripiprazole treatment. Because of the small sample size, further studies are needed to confirm and to extend our results.

摘要

引言

缬氨酸108/158蛋氨酸多态性(rs4680)可能会影响抗精神病药物的治疗反应,以及精神分裂症治疗期间神经递质的代谢和动力学。我们研究了缬氨酸108/158蛋氨酸多态性对急性精神分裂症患者阿立哌唑治疗反应及血浆单胺代谢物水平的影响。

材料与方法

40例精神分裂症患者接受阿立哌唑治疗6周。我们在基线和终点测量了阳性与阴性症状量表(PANSS)、血浆高香草酸(HVA)水平和血浆3-甲氧基-4-羟基苯乙二醇(MHPG)水平。采用聚合酶链反应和限制性片段长度多态性对缬氨酸108/158蛋氨酸多态性进行基因分型。

结果

PANSS总分和一般精神病理学评分存在显著的基因型-时间交互作用,蛋氨酸/蛋氨酸基因型显示出更大改善。阿立哌唑治疗反应率在缬氨酸108/158蛋氨酸基因型组之间无差异。我们发现血浆MHPG水平存在显著的时间效应,但血浆HVA水平无时间效应,且HVA和MHPG血浆水平无时间-基因型交互作用。尽管3个基因型组的缓解率无差异。

结论

我们的结果表明,蛋氨酸/蛋氨酸基因型个体在接受阿立哌唑治疗后PANSS评分改善更大。另一方面,缬氨酸108/158蛋氨酸多态性可能不会在阿立哌唑治疗期间引起血浆单胺代谢物水平的变化。由于样本量小,需要进一步研究来证实和扩展我们的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbd7/6018926/7a2817412945/ndt-14-1657Fig1.jpg

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