Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics.

Over the past several years, research has indicated that an individual's genetic makeup strongly influences not only their likelihood of developing depression, but also whether or not they will respond well to a particular antidepressant treatment. Identifying those genes regulating susceptibility to depression will increase our understanding of disease pathophysiology and direct the development of treatments that correct underlying neurobiological pathology related to stress-related psychiatric illnesses. Pharmacologically, the identification of genes regulating treatment response can lead to the design of novel pharmacological treatments and allow for more individualized, rational and successful drug treatments. Unfortunately, complex environmental and genetic mechanisms at play in depression and drug response make the discovery of susceptibility genes in humans quite difficult. Animal models may provide a more desirable system in which to discover susceptibility genes because environmental factors and tests can be regulated and more informative genetic methods can be used. Furthermore, a unique genetic opportunity exists with animal models of depression and antidepressant response because several rodent strains have been identified, or selectively bred, that display exaggerated depressive phenotypes on stress-related behavioral tests or divergent responses to antidepressant drugs. This paper reviews several of these rodent strains and illustrates the genetic strategies available to discover the long-sought susceptibility genes regulating these phenotypes.