Panic disorders: The role of genetics and epigenetics

Eun Jeong Kim, Yong-Ku Kim
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引用次数: 11

Abstract

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, NPY, ADORA2A, COMT, IKBKE. 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, NPY5R on 4q31.3-32, BDKRB2 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 SLC6a2 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.
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惊恐障碍:遗传学和表观遗传学的作用
摘要惊恐障碍的特点是突然出现恐惧,伴有心悸、出汗、颤抖和灼热感。考虑到其对每个人和社会的疾病负担,了解其病因很重要。尽管没有一种特定的病因是已知的,就像其他精神疾病一样,但已经提出了多种因素,如遗传、环境、神经生物学和精神病理学因素。在这篇文章中,我们回顾了目前已知的病因和相关研究结果,特别是关于惊恐障碍的遗传和表观遗传学方面。早期的研究,包括双胞胎研究、家庭研究和收养研究,都表明恐慌症具有高度的家族特征。连锁研究也发现,恐慌症不是一种单一的基因疾病,而是证实了多种相关基因的存在。染色体和候选基因研究发现很少有相关基因,如NPY、ADORA2A、COMT、IKBKE。新的方法,全基因组关联研究(GWAS)一直在寻找新的基因。然而,没有检测到全基因组的显著基因,证实了先前已知的候选基因,4q31.3-32上的NPY5R,14q32上的BDKRB2。表观遗传学修饰也被研究用于许多不同的精神疾病。单胺氧化酶A(MAOA)低甲基化,加上负性生活事件,与惊恐障碍有关。谷氨酸脱羧酶1(GAD1)低甲基化在惊恐障碍患者中也是特异性的。还研究了去甲肾上腺素转运蛋白(NET)基因SLC6a2启动子甲基化的关系。总之,并没有特定的基因或表观遗传学模式可以完全解释惊恐障碍的病因。然而,与健康对照组相比,很少有基因和表观遗传学模式与恐慌症有强烈的相关性。考虑到其多变量背景,对更多人群的进一步研究可以证实目前的结果,并阐明恐慌症的病因。
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AIMS Genetics
AIMS Genetics GENETICS & HEREDITY-
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