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CHRNA7 基因拷贝数增益在青少年重性抑郁障碍和焦虑障碍中富集。

CHRNA7 copy number gains are enriched in adolescents with major depressive and anxiety disorders.

机构信息

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States; Department of Genome Sciences, University of Washington, Seattle, WA, 98195, United States.

Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States.

出版信息

J Affect Disord. 2018 Oct 15;239:247-252. doi: 10.1016/j.jad.2018.07.017. Epub 2018 Jul 11.

Abstract

OBJECTIVE

Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR encoded by the gene CHRNA7, have been implicated in behavior regulation in animal models. In humans, copy number variants (CNVs) of CHRNA7 are found in a range of neuropsychiatric disorders, including mood and anxiety disorders. Here, we aimed to determine the prevalence of CHRNA7 CNVs among adolescents and young adults with major depressive disorder (MDD) and anxiety disorders.

METHODS

Twelve to 21 year-old participants with MDD and/or anxiety disorders (34% males, mean ± std age: 18.9 ± 1.8 years) were assessed for CHRNA7 copy number state using droplet digital PCR (ddPCR) and genomic quantitative PCR (qPCR). Demographic, anthropometric, and clinical data, including the Beck Anxiety Index (BAI), Beck Depression Inventory (BDI), and the Inventory of Depressive Symptoms (IDS) were collected and compared across individuals with and without a CHRNA7 CNV.

RESULTS

Of 205 individuals, five (2.4%) were found to carry a CHRNA7 gain, significantly higher than the general population. No CHRNA7 deletions were identified. Clinically, the individuals carrying CHRNA7 duplications did not differ significantly from copy neutral individuals with MDD and/or anxiety disorders.

CONCLUSIONS

CHRNA7 gains are relatively prevalent among young individuals with MDD and anxiety disorders (odds ratio = 4.032) without apparent distinguishing clinical features. Future studies should examine the therapeutic potential of α7 nAChR targeting drugs to ameliorate depressive and anxiety disorders.

摘要

目的

神经元烟碱型乙酰胆碱受体(nAChRs),特别是由 CHRNA7 基因编码的α7 nAChR,在动物模型中被认为与行为调节有关。在人类中,CHRNA7 的拷贝数变异(CNVs)存在于一系列神经精神疾病中,包括情绪和焦虑障碍。在这里,我们旨在确定 CHRNA7 CNVs 在患有重度抑郁症(MDD)和焦虑障碍的青少年和年轻成年人中的患病率。

方法

12 至 21 岁的 MDD 和/或焦虑障碍患者(34%为男性,平均年龄±标准差:18.9±1.8 岁)使用液滴数字 PCR(ddPCR)和基因组定量 PCR(qPCR)评估 CHRNA7 拷贝数状态。收集人口统计学、人体测量学和临床数据,包括贝克焦虑指数(BAI)、贝克抑郁量表(BDI)和抑郁症状量表(IDS),并比较 CHRNA7 CNV 阳性和阴性个体之间的差异。

结果

在 205 名个体中,有 5 名(2.4%)携带 CHRNA7 增益,明显高于普通人群。未发现 CHRNA7 缺失。临床方面,携带 CHRNA7 重复的个体与 MDD 和/或焦虑障碍的无 CHRNA7 重复个体在临床上没有显著差异。

结论

CHRNA7 增益在患有 MDD 和焦虑障碍的年轻个体中相对常见(优势比=4.032),但没有明显的临床特征。未来的研究应检查靶向α7 nAChR 的药物治疗抑郁和焦虑障碍的潜在疗效。

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