Research on GxE in depression was essentially launched with a publication in Science in 2003. In this study, Caspi and colleagues78 used data from a 26-year longitudinal study in New Zealand to test whether a functional length polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) interacted with stressful life events to increase risk for depression. Results of the Caspi study suggested that individuals with at least one short (s) allele (i.e. who had the “s/s” or “s/l” genotype of the biallelic coded version) had more depression whether measured in terms of level of depressive symptoms, a depression diagnosis, or incident depression, as well as suicidality, in response to the number of stressful life events when compared to subjects who were not s allele carriers. They also found that s allele carriers had a greater probability of experiencing depression relative to those without an s allele as a result of exposure to probable or severe childhood maltreatment. The Caspi paper has become one of the most influential studies in the field, having been cited more than 5,000 times.
