In humans, the risk for major depression in s allele carriers is particularly associated with both early life stress and repeated stress exposures, suggesting that stress will be experienced across childhood and adolescence in these subjects (Karg et al., 2011), thus it is possible that negative interaction effects associated with reduced 5-HTT expression are greater for stressors occurring across the pre- or post-weaning period or indeed prenatally. This evidence concerns the gene SLC6A4 and major depressive disorder.