There has been considerable speculation that gene–environment interactions are particularly salient for MDD. It is possible that MDD can only be understood if genetic and environmental risk factors are modeled simultaneously. The most prominent example for MDD is the moderation of environmental stress by genetic variation in a functional polymorphism near the serotonin transporter (5-HTTLPR).81 As in the initial report in 2003, some evidence has supported this GxE interaction82,83 other analyses have not84,85 and the original finding (from a longitudinal study in Dunedin, New Zealand) did not replicate in an independent longitudinal study in Christchurch, New Zealand.86 A practical issue is again the tradeoff between relatively inexpensive, cross-sectional assessments of MDD case and control status and the detailed longitudinal data required to accurately characterize environmental stressors.
