Vol 8, No 4 - Stress
Past issues Contributors How to publish Contributions and comments Home
 
ecent advances in molecular genetics have stim- ulated basic and clinical research,and opened up access to hypothesis-driven and unbiased genetic approaches.With knowledge of the genes involved in complex basic func- tions like the stress response,and of multifactorial diseases like stress-related disorders,we can improve our under- standing of the mechanisms and moderators involved in the biology of normal and altered stress response,which in turn will help to identify new drug targets and inter- ventions for stress-related disorders. Stress response and stress-related disorders Though there is no generally accepted definition,stress is usually defined as a state of disturbed homeostasis evoking a multiplicity of somatic and mental adaptive reactions,which are summarized as stress response aim- C l i n i c a l  r e s e a r c h R Copyright © 2006 LLS SAS. All rights reserved www.dialogues-cns.org Genetics of stress response and stress-related disorders Marcus Ising,PhD;Florian Holsboer,MD,PhD Keywords:stress; cardiovascular disorder; bipolar disorder; unipolar depression; genetics; sympathetic system; hypothalamic-pituitary-adrenocortical axis; renin- angiotensin-aldosterone system Author affiliations:Max Planck Institute of Psychiatry, Munich, Germany Address for correspondence:Marcus Ising, PhD, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany (e-mail: ising@mpipsykl.mpg.de) 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 con- servative 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 sta- tistically 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. © 2006, LLS SAS Dialogues Clin Neurosci. 2006;8:433-444.