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CREB1 和 BDNF 基因多态性与惊恐障碍患者早期依他普仑治疗反应相关。

CREB1 and BDNF gene polymorphisms are associated with early treatment response to escitalopram in panic disorder.

机构信息

Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China.

Department of Psychiatry, College of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Mental Health Institute, Tianjin Anding Hospital, Tianjin 300222, China.

出版信息

J Affect Disord. 2021 Jan 1;278:536-541. doi: 10.1016/j.jad.2020.09.076. Epub 2020 Sep 24.

Abstract

OBJECTIVES

Increasing evidence shows that the alternations under escitalopram treatment for Panic disorder (PD) patients are related to the cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). We aimed to explore the single nucleotide polymorphisms (SNPs) of genes BDNF and CREB1 in the treatment response to escitalopram on PD.

METHODS

There were 80 PD patients with DSM-5 diagnosis and 78 healthy controls. All PD patients have received escitalopram treatment for consecutive 8 weeks. The Chinese version of Panic Disorder Severity Scale (PDSS-CV) and the Hamilton Anxiety Scale (HAMA-14) were used to evaluate the severity of panic and anxious symptoms for PD patients at baseline, week-2, week-4, and week-8, respectively. Four SNPs (rs11904814, rs6740584, rs2253206, and rs2551941) in CREB1 gene and rs6265 in BDNF gene were genotyped using matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS). Quantitative and binary genetic associations between SNPs and escitalopram treatment response were performed.

RESULTS

The comparisons of three genotypes in CREB1 SNPs rs11904814 and rs2551941 among the PDSS-CV responders showed significant differences at the end of week-2 (both p<0.05). The results remained significant after Bonferroni corrections. For candidate genes in our present study, the gene CREB1 SNP rs11904814 (p=0.007) was significantly associated with changes of PDSS-CV scores under escitalopram treatment for 12 weeks in PD patients. And the result was still significant after adjusting age and gender.

CONCLUSIONS

The findings provide preliminary evidence supporting the potential role of BDNF and CREB1 on a rapid response after escitalopram intervention in PD patients.

摘要

目的

越来越多的证据表明,依他普仑治疗惊恐障碍(PD)患者的改变与环磷腺苷反应元件结合蛋白(CREB)和脑源性神经营养因子(BDNF)有关。我们旨在探索 BDNF 和 CREB1 基因的单核苷酸多态性(SNP)与依他普仑治疗 PD 的反应之间的关系。

方法

共有 80 例符合 DSM-5 诊断的 PD 患者和 78 名健康对照者。所有 PD 患者均接受依他普仑连续 8 周治疗。在基线、第 2 周、第 4 周和第 8 周,分别使用中文版惊恐障碍严重程度量表(PDSS-CV)和汉密尔顿焦虑量表(HAMA-14)评估 PD 患者惊恐和焦虑症状的严重程度。使用基质辅助激光解吸飞行时间质谱(MALDI-TOF MS)对 CREB1 基因中的 4 个 SNP(rs11904814、rs6740584、rs2253206 和 rs2551941)和 BDNF 基因中的 rs6265 进行基因分型。对 SNP 与依他普仑治疗反应之间的定量和二项遗传关联进行分析。

结果

在 PDSS-CV 应答者中,CREB1 SNP rs11904814 和 rs2551941 的三种基因型比较在第 2 周末时差异有统计学意义(均 p<0.05)。经过 Bonferroni 校正后,结果仍有统计学意义。在本研究的候选基因中,基因 CREB1 SNP rs11904814(p=0.007)与依他普仑治疗 12 周后 PD 患者 PDSS-CV 评分的变化显著相关。并且在调整年龄和性别后,结果仍然显著。

结论

这些发现为 BDNF 和 CREB1 基因在依他普仑干预 PD 患者后快速反应中的潜在作用提供了初步证据。

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