Department of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48149 Muenster, Germany.
Neuroimage. 2010 Nov 15;53(3):822-31. doi: 10.1016/j.neuroimage.2009.11.042. Epub 2009 Nov 26.
Anxiety disorders are frequent and burdensome psychiatric diseases. Despite their moderate to strong heritabilities, the search for candidate genes has been limited by methodological shortcomings hitherto, e.g., the use of clinically defined, but neurobiologically heterogeneous categorical phenotypes. Investigating neurobiological response patterns associated with fear processing as an intermediate phenotype might aid in overcoming these difficulties. The existing imaging literature on the neurobiological correlates of fear processing and anxiety disorders points to a pivotal role of the amygdala in the human fear circuit. Therefore, amygdala responsiveness to anxiety-related stimuli was suggested as an intermediate phenotype for anxiety disorders. The present article provides an overview of imaging genetic studies investigating genetic effects on amygdala responsiveness with particular emphasis on recent imaging genetic findings in anxiety-related traits, panic disorder and social phobia. The existing studies consistently reveal strong genetic effects on the responsiveness of the fear circuit, particularly of genetic variants previously discussed as potential susceptibility variants for anxiety, e.g., the COMT 158val allele or the 5-HTTLPR short allele. Further research will be necessary involving larger sample sizes to allow for investigating gene-gene and gene-environment interactions. More evolved statistical and neuroimaging methods such as effective connectivity measures could lead to a better understanding of imaging endophenotypes and the nature of gene-brain relationships. Longitudinal studies in patient samples will be required to elucidate how genetically influenced neurobiological intermediate phenotypes are associated with subtype, severity and the course of anxiety disorders, thereby having the potential for developing individualized therapy regimes derived from neurobiological research.
焦虑障碍是常见且负担沉重的精神疾病。尽管它们具有中度到高度的遗传可能性，但迄今为止，由于方法学上的缺陷，对候选基因的研究一直受到限制，例如使用临床定义但神经生物学上异质的分类表型。研究与恐惧处理相关的神经生物学反应模式作为中间表型可能有助于克服这些困难。关于恐惧处理和焦虑障碍的神经生物学相关性的现有影像学文献指出，杏仁核在人类恐惧回路中起着关键作用。因此，杏仁核对与焦虑相关刺激的反应性被认为是焦虑障碍的中间表型。本文概述了研究遗传对杏仁核反应性影响的影像学遗传学研究，特别强调了与焦虑相关特征、惊恐障碍和社交恐惧症的最近影像学遗传学发现。现有研究一致表明，恐惧回路的反应性具有强烈的遗传效应，特别是先前被认为是焦虑潜在易感性变异的遗传变异，例如 COMT 158val 等位基因或 5-HTTLPR 短等位基因。需要进一步进行更大样本量的研究，以调查基因-基因和基因-环境相互作用。更先进的统计和神经影像学方法，如有效连接测量，可以更好地理解影像学内表型和基因-大脑关系的本质。需要在患者样本中进行纵向研究，以阐明受遗传影响的神经生物学中间表型与焦虑障碍的亚型、严重程度和病程之间的关系，从而有可能从神经生物学研究中开发出针对个体的治疗方案。
