Genetics of stress response and stress-related disorders

The major findings regarding the genetics of stress response and stress-related disorders are: (i) variations in genes involved in the sympathetic system or in the hypothalamic-pituitary-adrenocortical axis are associated with altered stress responses; (ii) genes related to the renin-angiotensin-aldosterone system or inflammation/immune response show associations with cardiovascular disorders; (iii) genes involved in monoaminergic neurotransmitter systems are associated with bipolar disorder and unipolar depression. The vast majority of these association studies followed a conventional hypothesis-driven approach, restricting the gene selection to established candidates. This very conservative approach retarded our understanding of the complex interplay between genetic factors, stress response, and stress-related disorders. Chip-based whole-genome technologies will open up access to new unbiased and statistically efficient approaches that will help to identify new candidate genes, which should be thoroughly validated in clinical and preclinical confirmatory studies. This, together with the use of new text--and information-mining tools, will bring us closer to integrating all the findings into sophisticated models delineating the pathways from genes to stress response and stress-related disorders.