In 2003, Caspi and colleagues reported evidence of a G×E interaction between 5-HTTLPR variation and stressful life events on depression [15], with nearly 5000 citations to date. Carriers of either one or two copies of the S allele of the 5-HTTLPR were reported to be more likely to develop major depressive disorder, increased depressive symptoms, and suicidality in response to stressful life events and, separately, child maltreatment than individuals homozygous for the L allele. Furthermore, there was evidence of a dose–response relationship, with risk of depression highest amongst those with two copies of the S allele compared to individuals with only one copy in the presence of stress.
