Major depression in response to stressful situations has been reported as more common among persons harboring a variant in the proximal 5' regulatory region of the gene encoding the serotonin-transporter protein (5-HTT) (the target of selective serotonin-reuptake inhibitors [SSRIs]) that modifies promoter activity. This variant, in the 5-HTT gene–linked promoter region (5-HTTLPR), modifies promoter activity and is associated with lower transcriptional efficiency of the 5-HTT gene, ultimately leading to fewer copies of the messenger RNA encoding the serotonin-transporter protein. This lower-expressing variant may be associated with the amygdala-mediated hyperresponsiveness of young children to frightened or frightening faces that can facilitate encoding of painful memories, leading to stress sensitivity in adulthood. This variant is also associated with a reduction of serotonin function in response to maternal deprivation in nonhuman primates, an effect that persists into adulthood. An induced functional deficiency of the 5-HTT protein that is confined to the early postnatal period in mice results in altered behavior when they are grown, indicating possible changes in brain development that affect adult behavior.