reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA (Caldji et al., in press). In humans, children exposed to parenting characterized by conflict, aggression, and neglect show disruptions in stress-responsive biological regulatory systems (sympathetic-adrenomedullary, HPA), poor health behaviors, and poor skills for emotional and social regulation (Repetti et al., in press). Abusive and neglectful family environments not only enhance risk for disease, injury, and premature death among children, they also interact with temperament to affect a broad array of mental and physical health disorders in adolescence and adulthood, including propensity for violence, depression, and risk for certain chronic diseases, including ischemic heart disease, some cancers, liver disease, and chronic obstructive pulmonary disease, a progressive disease process most commonly resulting from smoking (e.g.; Felitti et al., 1998; Walker et al., 1999).

Other early system dysregulations also are implicated in predisease pathways to adverse outcomes. Serotonergic dysregulation has been tied to enhanced risk for depression, suicide, and aggression, among other adverse outcomes. For example, depressed abused children showed elevated prolactin responses to a serotonin challenge, and those responses were correlated with clinical ratings of aggressive behavior and family history of suicide attempt (Kaufman et al., 1998). Animal studies suggest an important role for maternal behavior in moderating risk for serotonergic dysregulation. Here genetic risk factors play a role. For example, the short form of the 5-HTT allele, a gene related to serotonin transporter efficiency, confers low serotonin reuptake efficiency in monkeys, whereas the long form of the allele is associated with normal serotonin reuptake efficiency (Suomi, 1997). Monkeys with the short 5-HTT allele who were raised by peers (a risk factor for reactive, impulsive temperament) showed lower concentrations of the primary central serotonin metabolite (5-HIAA) than did monkeys with the long allele. But for monkeys raised by their mothers, primary serotonin metabolite concentrations were identical for monkeys with either allele. This pattern clearly suggests a protective effect of maternal behavior on expression of genetic risk for serotonin dysfunction.

Additional evidence for the interaction between genetic expression and early experience is provided by a study that randomly assigned rhesus monkey neonates selectively bred for differences in temperamental reactivity to foster mothers who were either unusually nurturant or within the normal range of mothering behavior (Suomi, 1987). Infants whose pedigrees suggested normal reactivity exhibited the expected patterns of biobehavioral development, independent of the relative nurturance of the fos-

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