Don't worry; be informed about the epigenetics of anxiety.
Don't worry; be informed about the epigenetics of anxiety.
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DOI：
10.1016/j.pbb.2016.05.006
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Kosten TA
中科院分区：
文献类型：
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作者：
Nieto SJ;Patriquin MA;Nielsen DA;Kosten TA
表观遗传过程独立于DNA序列调节基因表达，并且越来越多地被研究为行为障碍发展的贡献者。环境损伤，如压力，饮食或毒素暴露，可以影响表观遗传机制，包括染色质重塑，DNA甲基化和非编码RNA，反过来，改变生物体的表型。在这篇综述中，我们检查了文献，来自临床前（动物）和临床（人类）水平，与焦虑症相关的表观遗传学改变。利用焦虑的动物模型，研究人员已经确定了已知与压力和情绪反应有关的几个边缘系统和皮质脑区域的表观遗传变化。在怀孕前、产前或产后早期以及少年和成年时，都对环境进行了操纵。扰动时间差异影响表观基因组，许多变化是大脑区域特异性的。虽然在动物研究中报告了一些性别依赖性效应，但需要更多的研究，特别是考虑到女性表现出不成比例的焦虑症。人类文献还处于起步阶段，但确实揭示了焦虑行为和障碍的一些表观遗传关联。特别是，在单胺能系统中的作用与病因学和治疗研究的证据一致。此外，有证据表明，表观遗传变化可能会遗传，影响后代。我们推测表观遗传过程如何与遗传贡献相互作用，为那些有焦虑症风险或患有焦虑症的人提供预防和治疗策略。
Epigenetic processes regulate gene expression independent of the DNA sequence and are increasingly being investigated as contributors to the development of behavioral disorders. Environmental insults, such as stress, diet, or toxin exposure, can affect epigenetic mechanisms, including chromatin remodeling, DNA methylation, and non-coding RNAs that, in turn, alter the organism’s phenotype. In this review, we examine the literature, derived at both the preclinical (animal) and clinical (human) levels, on epigenetic alterations associated with anxiety disorders. Using animal models of anxiety, researchers have identified epigenetic changes in several limbic and cortical brain regions known to be involved in stress and emotion responses. Environmental manipulations have been imposed prior to conception, during prenatal or early postnatal periods, and at juvenile and adult ages. Time of perturbation differentially affects the epigenome and many changes are brain region-specific. Although some sex-dependent effects are reported in animal studies, more research employing both sexes is needed particularly given that females exhibit a disproportionate number of anxiety disorders. The human literature is in its infancy but does reveal some epigenetic associations with anxiety behaviors and disorders. In particular, effects in monoaminergic systems are seen in line with evidence from etiological and treatment research. Further, there is evidence that epigenetic changes may be inherited to affect subsequent generations. We speculate on how epigenetic processes may interact with genetic contributions to inform prevention and treatment strategies for those who are at risk for or have anxiety disorders.