Gottschalk Michael G, Domschke Katharina
Department of Psychiatry, University of Würzburg, Würzburg, Germany.
Curr Opin Psychiatry. 2016 Jan;29(1):32-8. doi: 10.1097/YCO.0000000000000219.
The present review aims to deliver a systematic overview of current developments and trends in (epi)genetics of anxiety and to identify upcoming challenges and opportunities.
Genes related to peptide and hormone signaling have been suggested for anxiety-related phenotypes, e.g., the NPSR1 gene, which has been associated predominantly with panic disorder in women, and shown to interact with environmental factors and to influence psychometric, neurophysiological, and neuroimaging correlates of anxiety. Similar multi-level results have been reported for genetic and epigenetic variation in the OXTR gene, especially in social anxiety disorder (SAD), and for CRHR1 gene variation in women with panic disorder. Variants in RGS2 and ASIC1 genes were linked to panic disorder, with the latter also being implicated in SAD treatment response. Finally, monoaminergic 'risk' genes (SLC6A4, MAOA, HTR1A) were related to SAD, generalized anxiety disorder and women with panic disorder, anxiety traits and response to psychopharmacological and psychotherapeutic interventions.
Converging evidence for potential genetic and epigenetic risk markers has been gathered and future studies call for independent replications and multi-level integration of dimensional approaches, environmental factors, and biological readouts, while considering sex-specific substratification. Particularly, epigenetic variation appears promising for disease course and treatment response predictions.
本综述旨在系统概述焦虑症（表观）遗传学的当前发展和趋势，并确定即将面临的挑战和机遇。
已提出与肽和激素信号传导相关的基因与焦虑相关表型有关，例如NPSR1基因，该基因主要与女性惊恐障碍相关，并显示出与环境因素相互作用，影响焦虑的心理测量、神经生理学和神经影像学相关性。对于OXTR基因的遗传和表观遗传变异，特别是在社交焦虑障碍（SAD）中，以及惊恐障碍女性中的CRHR1基因变异，也报道了类似的多水平结果。RGS2和ASIC1基因的变异与惊恐障碍有关，后者也与SAD治疗反应有关。最后，单胺能“风险”基因（SLC6A4、MAOA、HTR1A）与SAD、广泛性焦虑障碍以及惊恐障碍女性、焦虑特质以及对心理药理学和心理治疗干预的反应有关。
已经收集了关于潜在遗传和表观遗传风险标志物的越来越多的证据，未来的研究需要进行独立复制，并对维度方法、环境因素和生物学读数进行多水平整合，同时考虑性别特异性分层。特别是，表观遗传变异在疾病进程和治疗反应预测方面似乎很有前景。
