A first implication is that research on environmental risks can be constructively integrated with genetics to illuminate the etiology of depression. Previous studies have reported that childhood maltreatment is strongly and directly related to persistent forms of adult depression (Brown et al., 2008; Wiersma et al., 2009). The present study extends this observation to suggest that 5-HTTLPR confers sensitivity to childhood maltreatment in relation to developing persistent depression. This finding may help to shed light on the problem of “missing heritability” in psychiatric illness (Manolio et al., 2009; Uher, 2009). Twin studies have reported that depression diagnosed on at least two occasions is strongly heritable (Foley et al., 1998; McGuffin et al., 1996), but no genetic polymorphism has been unequivocally linked to this phenotype (Lewis et al., 2010; Muglia et al., 2010; Shi et al., 2010; Sullivan et al., 2009). Since the heritability estimate in twin design includes variation due to interactions between genes and shared environment (Uher, 2008, 2009), and since experiences of maltreatment are often shared by siblings growing up in the same family (Brown et al., 2007;
