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140 EFFECTS OF EARLY MALTREATMENT AND STRESSthe HPA axis may result in patterns of stress-system functioning that are associatedwith and may contribute to these children’s behavior problems.Although there are certainly gaps in our knowledge, one is of particular concernto the focus of this book. Specifically, we have very little prospective informationabout the impact of early adversity on stress reactivity and regulation aschildren transition into and through adolescence. This may be particularly importantas there is evidence that the pubertal transition is associated with rising cortisollevels and possibly more neuroendocrine reactivity to psychosocial stressors(for review, see Gunnar & Vazquez, 2006; Spear, 2000). It is possible that impactsof early adversity on the development of the stress-emotion system mayincrease in its influence on health and emotional functioning with the adolescent/pubertal shift in life circumstances and biological functioning.Intervention StudiesNot surprising, given that we are just beginning to document the impact of earlypsychosocial adversity on the developing stress-emotion system in human children,intervention studies in this area are scarce. Nonetheless, we can infer from studiesof PI children that being placed in a family has significant impacts. Toddlers studiedwhile they were in an orphanage in Romania failed to exhibit the normal diurnalrhythm in cortisol production over the day (Carlson & Earls, 1997). We obtainedsimilar results in an orphanage in Russia (Kroupina, Gunnar, & Johnson, 1997). Inboth institutions, the children tended to have low early morning cortisol levels andslightly, but not significantly, higher noon and evening levels. There is increasingevidence that low levels of cortisol at the peak of the diurnal cycle may reflect chronicstress (Freese, Hesse, Hellhammer, & Hellhammer, 2005). Low early A.M. cortisollevels result in a flat pattern of cortisol production across the day, which amongadults has been associated with chronic idiopathic pain disorders and chronic fatiguesyndrome (Heim, Ehlert, & Hellhammer, 2000).Among nonhuman primates, rhesus infants have been shown to develop similardisturbances in HPA axis rhythmicities when exposed to repeated (36), brief(30 min to 6 hr), unpredictable maternal separations between 3 and 6 months ofage (Sanchez et al., 2005). Notably, in the monkey research, maternal responsivityto the infant at reunion reduced the impact of separation on diurnal cortisol production,and more disrupted cortisol rhythms predicted larger startle reactions (anindex of amygdala reactivity) when the animals were 22 months of age. Thus, adisturbed diurnal HPA axis rhythm may be a biomarker of HPA axis dysregulation(see also Gunnar & Vazquez, 2001).If so, and if most children in orphanages exhibit this form of stress systemdysregulation, then adoption is an effective intervention. In all of the studies wehave conducted with PI children we have yet to find a child that shows the flat