Domschke Katharina, Reif Andreas
Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, D-97080, Würzburg, Germany,
Curr Top Behav Neurosci. 2012;12:463-502. doi: 10.1007/7854_2011_185.
As shown by clinical genetic studies, affective and anxiety disorders are complex genetic disorders with genetic and environmental factors interactively determining their respective pathomechanism. Advances in molecular genetic techniques including linkage studies, association studies, and genome-wide association studies allow for the detailed dissection of the genetic influence on the development of these disorders. Besides the molecular genetic investigation of categorical entities according to standardized diagnostic criteria, intermediate phenotypes comprising neurobiological or neuropsychological traits (e.g., neuronal correlates of emotional processing) that are linked to the disease of interest and that are heritable, have been proposed to be closer to the underlying genotype than the overall disease phenotype. These intermediate phenotypes are dimensional and more precisely defined than the categorical disease phenotype, and therefore have attracted much interest in the genetic investigation of affective and anxiety disorders. Given the complex genetic nature of affective and anxiety disorders with an interaction of multiple risk genes and environmental influences, the interplay of genetic factors with environmental factors is investigated by means of gene-environment interaction (GxE) studies. Pharmacogenetic studies aid in the dissection of the genetically influenced heterogeneity of psychotropic drug response and may contribute to the development of a more individualized treatment of affective and anxiety disorders. Finally, there is some evidence for genetic factors potentially shared between affective and anxiety disorders pointing to a possible overlapping phenotype between anxiety disorders and depression.
临床遗传学研究表明，情感障碍和焦虑症是复杂的遗传疾病，遗传因素和环境因素相互作用决定了它们各自的发病机制。包括连锁研究、关联研究和全基因组关联研究在内的分子遗传学技术的进展，使得对这些疾病发展过程中遗传影响的详细剖析成为可能。除了根据标准化诊断标准对分类实体进行分子遗传学研究外，还提出了一些中间表型，这些表型包括与相关疾病相关且具有遗传性的神经生物学或神经心理学特征（例如，情绪加工的神经元关联），它们比整体疾病表型更接近潜在的基因型。这些中间表型是维度性的，比分类疾病表型定义更精确，因此在情感障碍和焦虑症的遗传学研究中引起了广泛关注。鉴于情感障碍和焦虑症具有复杂的遗传性质，涉及多个风险基因与环境影响的相互作用，基因-环境相互作用（GxE）研究对遗传因素与环境因素之间的相互作用进行了探究。药物遗传学研究有助于剖析受遗传影响的精神药物反应异质性，并可能有助于开发更具个性化的情感障碍和焦虑症治疗方法。最后，有证据表明情感障碍和焦虑症之间可能存在潜在的共同遗传因素，这表明焦虑症和抑郁症之间可能存在重叠的表型。
