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惊恐障碍:遗传学与表观遗传学的作用

Panic disorders: The role of genetics and epigenetics.

作者信息

Kim Eun Jeong, Kim Yong-Ku

机构信息

Department of Psychiatry, Korea University Ansan Hospital, Ansan, Republic of Korea.

出版信息

AIMS Genet. 2018 Jul 27;5(3):177-190. doi: 10.3934/genet.2018.3.177. eCollection 2018.

Abstract

Panic disorder is characterized by symptoms with abrupt surges of fear with palpitations, sweating, trembling, heat sensations. Considering its disease burden on each individual and on society, understanding its etiology is important. Though no one specific etiology has been known, like other psychiatric disorders, multiple factors such as genetic, environmental, neurobiological, psychopathological factors have been suggested. In this article, we reviewed currently known etiologies and related study results, regarding especially genetic and epigenetic aspects of the panic disorder. Early studies, including twin studies, family studies, adoption studies suggested highly familial trait of panic disorder. Linkage studies, either, found panic disorder is not a single gene disorder but confirmed existence of multiple related genes. Chromosome and candidate gene studies found few related genes, . Newer method, genome-wide association studies (GWAS) have been searching for newer genes. No genome-wide significant genes, however, were detected, confirming previously known candidate genes, on 4q31.3-32, on 14q32, instead. Epigenetic modification has also been studied on many different psychiatric disorders. Monoamine oxidase A (MAOA) hypomethylation, taken together with negative life events, showed relation with panic disorder. Glutamate decarbodylases 1 (GAD1) hypomethylation was also specific on panic disorder patients. Relation with noradrenaline transporter (NET) gene promoter methylation has also been studied. In conclusion, no specific gene or epigenetic pattern can fully explain etiology of panic disorder. Few genes and epigenetic patterns, however, showed strong association with panic disorder compared to healthy controls. Considering its multivariable background, further studies with larger populations can confirm current results and clarify etiologies of panic disorder.

摘要

惊恐障碍的特征是突然发作的恐惧症状,伴有心悸、出汗、颤抖、发热感。鉴于其对个体和社会的疾病负担,了解其病因很重要。虽然尚未明确单一的特定病因,但与其他精神障碍一样,遗传、环境、神经生物学、精神病理学等多种因素已被提出。在本文中,我们回顾了目前已知的病因及相关研究结果,尤其关注惊恐障碍的遗传和表观遗传方面。早期研究,包括双胞胎研究、家族研究、收养研究,表明惊恐障碍具有高度的家族性特征。连锁研究也发现惊恐障碍不是单基因疾病,但证实了多个相关基因的存在。染色体和候选基因研究发现的相关基因较少。更新的方法,即全基因组关联研究(GWAS)一直在寻找新的基因。然而,未检测到全基因组显著的基因,而是证实了先前已知的位于4q31.3 - 32、14q32上的候选基因。表观遗传修饰也在许多不同的精神障碍中得到了研究。单胺氧化酶A(MAOA)低甲基化与负面生活事件共同作用,显示出与惊恐障碍的关联。谷氨酸脱羧酶1(GAD1)低甲基化在惊恐障碍患者中也具有特异性。与去甲肾上腺素转运体(NET)基因启动子甲基化的关系也已被研究。总之,没有特定的基因或表观遗传模式能够完全解释惊恐障碍的病因。然而,与健康对照相比,少数基因和表观遗传模式与惊恐障碍显示出强烈的关联。考虑到其多变量背景,进一步的大样本研究可以证实当前结果并阐明惊恐障碍的病因。

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