Smoller J W, Tsuang M T
Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA.
Am J Psychiatry. 1998 Sep;155(9):1152-62. doi: 10.1176/ajp.155.9.1152.
With recent advances in molecular genetics, the rate-limiting step in identifying susceptibility genes for psychiatric disorders has become phenotype definition. The success of psychiatric genetics may require the development of a "genetic nosology" that can classify individuals in terms of the heritable aspects of psychopathology. The authors' aim is to begin to apply this analysis to the anxiety disorders, focusing on panic and phobic disorders.
Two parallel traditions of defining anxiety phenotypes are reviewed: the first, more closely identified with clinical psychiatry, has identified categorical diagnoses (e.g., panic disorder and social phobia). The other, more closely identified with psychological studies of personality development, has examined dimensional traits (e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition).
The authors suggest that a genetic nosology of panic and phobic disorders may incorporate features of both traditions and discuss strategies for optimizing genetic approaches to anxiety including 1) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci.
An important dividend from the effort to define the boundaries of heritable phenotypes for genetic studies of anxiety may be a refinement of the nosology of anxiety disorders.
随着分子遗传学的最新进展，确定精神疾病易感性基因的限速步骤已成为表型定义。精神遗传学的成功可能需要发展一种“遗传疾病分类学”，它能够根据精神病理学的遗传方面对个体进行分类。作者的目的是开始将这种分析应用于焦虑症，重点关注惊恐障碍和恐惧症。
回顾了定义焦虑症表型的两种平行传统：第一种与临床精神病学联系更紧密，确定了分类诊断（如惊恐障碍和社交恐惧症）。另一种与人格发展的心理学研究联系更紧密，研究了维度特征（如神经质）和焦虑气质（如行为抑制）。
作者认为，惊恐障碍和恐惧症的遗传疾病分类学可能融合这两种传统的特征，并讨论了优化焦虑症遗传研究方法的策略，包括1）研究表型极端情况，2）识别生物学特征标记，3）使用动物模型识别候选基因座。
为焦虑症遗传研究界定可遗传表型边界的努力带来的一个重要好处可能是焦虑症疾病分类学的完善。
