Gottschalk Michael G, Domschke Katharina
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.
Department of Psychiatry and Psychotherapy, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
Dialogues Clin Neurosci. 2017 Jun;19(2):159-168. doi: 10.31887/DCNS.2017.19.2/kdomschke.
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, ) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework. We explore etiologic factors in gene-environment interaction approaches investigating childhood trauma, environmental adversity, and stressful life events in relation to selected candidate genes (), Additionally, the pharmacogenetics of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor treatment are summarized (). Finally, GAD and trait anxiety research challenges and perspectives in the field of genetics, including epigenetics, are discussed.
本综述是对广泛性焦虑症（GAD）遗传学的系统指南，并进一步聚焦于与焦虑相关的内表型，如病理性担忧、对不确定性的恐惧和神经质。我们基于家系和双生子研究，考察GAD家族性和遗传性以及跨疾病表型的临床遗传学证据。概述了连锁研究、全基因组关联研究和候选基因研究（如……）的最新进展。进一步整合了与外周应激标志物和心理生理学相关的功能和结构神经影像学及神经生理学指标，构建了一个多层次的疾病框架。我们在基因-环境相互作用方法中探究病因因素，研究童年创伤、环境逆境和应激性生活事件与选定候选基因（……）的关系。此外，总结了选择性5-羟色胺再摄取抑制剂/5-羟色胺-去甲肾上腺素再摄取抑制剂治疗的药物遗传学（……）。最后，讨论了GAD和特质焦虑在遗传学领域（包括表观遗传学）的研究挑战和前景。
