In this study, measures of the quality and availability of social supports were found to moderate risk for depression associated with a history of maltreatment and the presence of the short (s) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR). The present investigation (i) replicates research in adults showing that 5-HTTLPR variation moderates the development of depression after stress, (ii) extends the finding to children, and (iii) demonstrates the ability of social supports to further moderate risk for depression. Maltreated children with the s͞s genotype and no positive supports had the highest depression ratings, scores that were twice as high as the non-maltreated comparison children with the same genotype. However, the presence of positive supports reduced risk associated with maltreatment and the s͞s genotype, such that maltreated children with this profile had only minimal increases in their depression scores. These findings are consistent with emerging preclinical and clinical data suggesting that the negative sequelae associated with early stress are not inevitable. Risk for negative outcomes may be modified by both genetic and environmental factors, with the quality and availability of social supports among the most important environmental factors in promoting resiliency in maltreated children, even in the presence of a genotype expected to confer vulnerability for psychiatric disorder.child maltreatment ͉ gene-by-environment interaction C hild abuse is a pervasive societal problem, with nearly 1 million substantiated reports of child maltreatment each year (1), many reported cases of actual abuse that are not verified (2), and countless other cases that never come to the attention of authorities (3). Although not all abused children develop difficulties, many experience a chronic course of psychopathology, with depression as one of the most common psychiatric sequelae reported in maltreated children (4, 5).Preclinical studies suggest that stress early in life can promote long-term changes in multiple neurochemical systems (6, 7). Specifically, exposure to prenatal and͞or postnatal stress is associated with increased basal and stress-induced responsiveness of the hypothalamic pituitary adrenal axis, increased central corticotropin-releasing hormone and norepinephrine drive, decreased ␥-aminobutyric acid͞benzodiazepine functioning, multiple alterations in the serotonergic system, and reduction in hippocampal volume, a brain structure vulnerable to the neurotoxic effects of stress-induced elevations in circulating glucocorticoids (e.g., cortisol) and amino acids (e.g., glutamate).Because many of the biological alterations associated with early stress in preclinical studies have been reported in adults with depression, it has been hypothesized that the neurobiological changes associated with adverse early experiences may confer a vulnerability for the development of depression (6,8). Consistent with preclinical studies, adults with depression have been reported to have multiple ...