Molecular genetics of anxiety in mice and men

Human anxiety disorders represent one of the most common mental illnesses. They are complex diseases with both genetic and environmental factors affecting their predisposition. Since the basic neuronal mechanisms are shared across mammalian species, the same set of genes may regulate critical aspects of anxiety in humans and in lower species. In this review, we first summarize findings from human molecular genetic approaches to anxiety disorders or anxiety-related personality traits: genome-wide scans and candidate gene studies in large families or case-control cohorts. We then discuss recent studies that have used genome-wide methods in mouse strains to identify genes that regulate anxiety-like behavior. Although it has been difficult to pinpoint specific susceptibility genes for anxiety disorders, ongoing efforts to collect larger study cohorts and to develop new genetic tools should help in this task. Studies in animals have shown that novel quantitative trait locus (QTL) and functional genomics approaches might lead to the identification of regulators of anxiety in mice, and that these genes can be tested for their involvement in human anxiety disorders. Finally, breakthroughs are expected in the fine-mapping of human and mouse genetic linkage regions and in the identification of novel candidate genes using genome-wide methods in mouse models of anxiety.