This is the first revision of a proposal to study the effects of early life stress (ELS) in the form of orphanage/institutional rearing on children's threat- and stress-response systems and aspects of parenting post-adoption that support recovery of these systems and decreases subsequent risk of emotional and attentional problems. 150 children internationally-adopted from orphanages/institutions and their families will be studied at four 8-mo intervals beginning 2 mos post-adoption for the child's first 2 yrs in the family with a 5th outcome assessed at 4.5-5.5. yrs (2.5-3.5 yrs post-adoption). Previous work documents the first yrs post-adoption as ones of rapid rebound/recovery. However, children adopted post-infancy (18-30 mos in this study) exhibit great heterogeneity in outcomes. Based on animal studies of ELS, we will test the hypothesis that sensitization of threat- and stress-response system functioning at adoption and the capacity of these systems to recover underlies heterogeneity in emotional and attentional problems. Further, we will test the hypothesis that variations in post-adoption parenting interacts with sensitization of these systems to affect recovery trajectories. A multi-method, multi-level approach will be used with home and laboratory assessments of behavioral and physiological indices of threat- and stress-system functioning: behavioral measures of negative emotionality, salivary measures of cortisol, and electrophysiological measures of ANS functioning. Outcome measures will include parent, teacher and child reports augmented by laboratory assessments of EEG power and asymmetry, fear-potentiated startle (EMG startle), and ERP and behavioral measures of executive attention. Parent behavior will be assessed using structured laboratory assessments and measures derived from parent diary reports. Finally, we will also explore whether the serotonin transporter gene polymorphism, shown to moderate risk for depression in maltreated children and HPA axis reactivity in animal models, moderates children's vulnerability to early institutional care and/or capacity to recover. The ultimate goals of this work are (1) to establish a better understanding of the mechanisms through which early life stress increases risks of emotional and behavioral problems, (2) identify children at the greatest risk of emotional and attentional problems and (3) identify patterns of parenting to target in subsequent randomized intervention trials to improve outcomes for these and similar children. PUBLIC HEALTH RELEVANCE: The proposed study examines effects of early life stress (ELS) in the form of orphanage/institutional rearing on children's threat- and stress-response systems and aspects of parenting post-adoption that support recovery of these systems and decrease subsequent risk of emotional and attentional problems. The goals of this work are (1) to establish a better understanding of the mechanisms through which early life stress increases risks of emotional and behavioral problems, (2) identify children at the greatest risk of emotional and attentional problems and (3) identify patterns of parenting to target in subsequent randomized intervention trials to improve outcomes for these and similar children.