On the other hand, some have argued that support for the 5HTTLPR GxE has been more consistent when childhood maltreatment is the exposure variable83-85 or when direct-interview assessments (as opposed to self-report questionnaires) have been used.84,85 This finding is important, as there has been substantial variability in the characteristics of study populations, measurements of depression and environmental exposures, and analytic methods used across empirical studies to test for GxE in depression.72 Some have also tried to place these individual GxE studies in the context of the broader literature examining genetic variability and stress sensitivity on depression. Here, some have appealed to the more consistent findings from animal studies showing that loss of function mutations in the serotonin gene have been associated with depressive-like behavior in rodents and that genetic variation in the serotonin transporter gene has been linked to depression among non-human primates.93 Proponents have also noted that the results are more convincing when considered alongside experimental imaging studies showing 5-HTTLPR variation in amygdala activity, and treatment response studies showing 5-HTTLPR variation in antidepressant treatment response.93,94 Overall, the validity of the influential 5-HTTLPR GxE finding remains unclear.
