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Objective: To examine the impact of the catechol-O-methyltransferase (COMT) val[superscript 158]met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions. Methods: One hundred thirty six children from the Bucharest Early Intervention Project (BEIP) were randomized before 31 months of age to either care as usual (CAU) in institutions or placement in newly created foster care (FCG). At 54 months of age, a psychiatric assessment using the Preschool Age Psychiatric Assessment (PAPA) was completed. DNA was collected and genotyped for the COMT val[superscript 158]met polymorphism. Multivariate analysis examined the relationship between COMT alleles and depressive symptoms. Results: Mean level of depressive symptoms was lower among participants with the met allele compared to those with two copies of the val allele (P less than 0.05). Controlling for group and gender, the rate of depressive symptoms was significantly lower among participants with the met/met or the met/val genotype [adjusted relative risk (aRR) = 0.67, 95% CI = 0.45, 0.99] compared to participants with the val/val genotype, indicating an intermediate impact for heterozygotes consistent with the biological impact of this polymorphism. The impact of genotype within groups differed significantly. There was a significant protective effect of the met allele on depressive symptoms within the CAU group, however there was no relationship seen within the FCG group. Conclusions: This is the first study, to our knowledge, to find evidence of a gene x environment interaction in the setting of early social deprivation. These results support the hypothesis that individual genetic differences may explain some of the variability in recovery amongst children exposed to early severe social deprivation. (Contains 3 tables and 1 figure.)

Objectives: To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence., Study Design: This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development., Results: Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with ≥2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with ≥2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions., Conclusions: For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental., Trial Registration: clinicaltrials.gov: NCT00747396., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To test whether genotype of the serotonin transporter-linked polymorphic region (5HTTLPR) and atypical attachment interact to predict externalizing psychopathology prospectively in a sample of children with a history of early institutional care., Methods: Caregiver report of externalizing behavior at 54 months was examined in 105 children initially reared in institutional care and enrolled in the Bucharest Early Intervention Project, a randomized controlled trial of high quality foster care. 5HTTLPR genotype, attachment status at 42 months of age (typical [secure, avoidant, or ambivalent] or atypical [disorganized-controlling, insecure-other]), and their interaction were examined as predictors of externalizing behavior at age 54 months., Results: 5HTTLPR genotype and atypical attachment at age 42 months interacted to predict externalizing behavior at age 54 months. Specifically, children with the s/s genotype with an atypical attachment had the highest externalizing scores. However, s/s children with a typical attachment demonstrated the lowest externalizing scores, even after controlling for intervention group status. There was no association between attachment status and externalizing behavior among children carrying at least 1 copy of the l allele., Conclusion: These findings indicate that genetic variation in the serotonergic system moderates the association between atypical attachment status and externalizing in young children. Our findings suggest that children, as a result of genetic variability in the serotonergic system, demonstrate differential sensitivity to the attachment relationship.

Objective: Children exposed to early institutional rearing are at risk for developing psychopathology. The present investigation examines caregiving quality and the role of attachment security as they relate to symptoms of psychopathology in young children exposed to early institutionalization., Method: Participants were enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal intervention study of children abandoned and placed in institutions at or shortly after birth. Measures included observed caregiving when children were 30 months of age, observed attachment security at 42 months, and caregiver reports of children's psychopathology at 54 months. At 54 months, some children remained in institutions, others were in foster care, others had been adopted domestically, and still others had been returned to their biological families. Thus, the children had experienced varying amounts of institutional rearing., Results: After controlling for gender, quality of caregiving when children were 30 months old was associated with symptoms of multiple domains of psychopathology at 54 months of age. Ratings of security of attachment at 42 months mediated the associations between quality caregiving at 30 months and fewer symptoms of psychopathology at 54 months., Conclusions: Among deprived young children, high-quality caregiving at 30 months predicted reduced psychopathology and functional impairment at 54 months. Security of attachment mediated this relationship. Interventions for young children who have experienced deprivation may benefit from explicitly targeting caregiver-child attachment relationships., (Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The authors examined signs of emotionally withdrawn (inhibited type) and indiscriminately social (disinhibited type) reactive attachment disorder in Romanian children enrolled in a randomized trial of foster care compared with institutional care and in a comparison group of never-institutionalized children., Method: At baseline and when children were ages 30, 42, and 54 months and 8 years, caregivers were interviewed with the Disturbances of Attachment Interview to assess changes in signs of reactive attachment disorder in three groups of children: those receiving care as usual (including continued institutional care) (N=68); those placed in foster care after institutional care (N=68); and those who were never institutionalized (N=72). The impact of gender, ethnicity, and baseline cognitive ability was also examined., Results: On the Disturbances of Attachment Interview, signs of the inhibited type of reactive attachment disorder decreased after placement in foster care, and scores were indistinguishable from those of never-institutionalized children after 30 months. Signs of the disinhibited type were highest in the usual care group, lower in the foster care group, and lowest in the never-institutionalized group. Early placement in foster care (before age 24 months) was associated with fewer signs of the disinhibited type. Lower baseline cognitive ability was associated with more signs of the inhibited type in the usual care group and more signs of the disinhibited type in both groups., Conclusions: Signs of the inhibited type of reactive attachment disorder responded quickly to placement in foster care; signs of the disinhibited type showed less robust resolution with foster placement. Lower baseline cognitive ability was linked to signs of reactive attachment disorder.

Children raised in institutions, considered an extreme example of social deprivation, are one group through which we can better understand the impact of neglect on child health and development. The Bucharest Early Intervention Project (BEIP) is the first randomized, controlled trial of foster care as an intervention for institutionalized children. In this review we describe the mental health outcomes from the BEIP. Specifically, we report findings on attachment styles, attachment disorders, emotional reactivity, and psychiatric symptomatology for children in the BEIP. We describe the impact of the foster care intervention on these outcomes and also describe how outcomes differ by gender and by length of time spent in the institution. In addition, we explore the influence of genetic variation on individual outcomes and recovery from early severe social deprivation, as well as the role of differences in brain development in mediating later psychiatric morbidity. The results from the BEIP confirm and extend the previous findings on the negative sequelae of early institutional care on mental health. The results also underscore the benefit of early family placement for children living in institutions.