Towards a genetics of anxious temperament: from mice to men

An enduring question in the study of human personality is 'to what extent and how do genetic factors influence such personality constructs as "trait anxiety"?'. We selectively survey progress and obstacles in the genetic dissection of fear-like behavior, especially as it pertains to more constitutional forms of anxiety or anxious temperament. We emphasize the selection of phenotypic dimensions and the utility of 'temperament' and personality constructs as mediating variables for psychopathology. We summarize studies on the use of mouse models of 'anxious temperament' to map genetic loci, and briefly review recent genetic association studies of related phenotypes in humans utilizing candidate genes. We suggest that further progress in genetic research on 'trait anxiety' disorders may come from the following: (i) developing alternate constructs for investigating psychiatric illness focusing on dimensional scales, mediating variables and premorbid traits; (ii) examining 'at-risk' populations for protective genetic factors influencing 'resilience' or loci providing a reduced risk of a given trait or disorder; and (iii) utilizing lower animal models as a bridge to dissect the genetic factors contributing to related human phenotypes.