Gene-environment interactions in depression research: genetic polymorphisms and life-stress polyprocedures

Recent studies on life stress, depression, and polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) are characterized by powerful genetic techniques, but are also characterized by unconventional and inconsistent approaches to assessing life stress. The present review addresses this problem by critically evaluating this rapidly growing literature with regard to the concepts and procedures employed to assess life stress and the research designs used to test causal associations. The existing body of evidence is seriously compromised by the predominance of ad hoc approaches for measuring life stress and by a lack of attention to key issues concerning research design. Principles and procedures for more refined and rigorous stress measurement are outlined. Improved guidelines are needed to direct future research on interactive effects of life stress and genes in psychopathology, pathophysiological processes, and disease.