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NRG1 多态性与未经治疗的精神分裂症患者利培酮的神经认知表现和临床症状反应的遗传关联。

Pharmacogenetic associations of NRG1 polymorphisms with neurocognitive performance and clinical symptom response to risperidone in the untreated schizophrenia.

机构信息

Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.

Department of Psychosomatic Medicine, Tongji University School of Medicine, Shanghai East Hospital, Shanghai, China.

出版信息

Schizophr Res. 2021 May;231:67-69. doi: 10.1016/j.schres.2021.03.001. Epub 2021 Mar 23.

Abstract

OBJECTIVE

To explore pharmacogenetic relationships of NRG1 genotypes with neurocognitive performance and clinical symptoms after 12 week treatment of risperidone in Chinese Han first-episode schizophrenia.

METHODS

A cohort of 221 patients with schizophrenia were recruited for this research. Finally 177 untreated first-episode patients were clinically evaluated with the Positive and Negative Syndrome Scale (PANSS), Raven's Standard Progressive Matrices (RSPM), Digit Vigilance Test (DVT), Digit Span (DS), underwent genotyping for five polymorphisms of NRG1, and completed a 12-week prospective study of risperidone monotherapy.

RESULTS

  1. After risperidone treatment of 12 weeks, the total scores, positive score, negative score and general score of PANSS decreased significantly; the scores of RSPM, DVT and DS increased significantly. 2. No significant association with PANSS scores at baseline or change in scores after 12 weeks'treatment was found with any of the five SNPs. There was also neither significant association of DVT, DS or RSPM at baseline with any of the five SNPs. 3. After risperidone treatment of 12 weeks, rs3924999 and rs35753505 showed significant association with change in DVT and in RSPM in which there were significant differences among different genotype groups.

CONCLUSION

This study suggested pharmacogenetic relationships between NRG1 variants and changes in cognition response with exposure to 12 weeks of treatment with risperidone. Two variants, rs3924999 and rs35753505, in the NRG1 gene were associated with the changes in attention and reasoning ability after risperidone treatment of 12 weeks.

摘要

目的

探讨 NRG1 基因型与利培酮治疗 12 周后中国汉族首发精神分裂症患者神经认知功能和临床症状的关系。

方法

本研究纳入了 221 例精神分裂症患者。最终,对 177 例未经治疗的首发精神分裂症患者进行了临床评估,使用阳性和阴性症状量表(PANSS)、瑞文标准推理测验(RSPM)、数字警戒测验(DVT)、数字跨度(DS)进行评估,对 NRG1 的 5 个多态性进行基因分型,并完成了为期 12 周的利培酮单药治疗前瞻性研究。

结果

  1. 利培酮治疗 12 周后,PANSS 总分、阳性症状评分、阴性症状评分和一般精神病理评分均显著下降;RSPM、DVT 和 DS 评分均显著升高。2. 5 个 SNP 与基线时 PANSS 评分或治疗 12 周后评分变化均无显著相关性。基线时 DVT、DS 或 RSPM 与 5 个 SNP 也无显著相关性。3. 利培酮治疗 12 周后,rs3924999 和 rs35753505 与 DVT 和 RSPM 的变化显著相关,不同基因型组之间存在显著差异。

结论

本研究提示 NRG1 变异与暴露于利培酮治疗 12 周后认知反应的变化存在药物遗传学关系。NRG1 基因中的两个变体 rs3924999 和 rs35753505 与利培酮治疗 12 周后注意力和推理能力的变化相关。

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