Panic and phobic anxiety: Defining phenotypes for genetic studies

Objective: 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. Method: 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). Results: 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 I) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci. Conclusions: 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.