The goal of this study was to examine the development of limbic structures and emotional behavior in children who experienced early-life adversity. An advantage of studying a population of children who have experienced orphanage care and have subsequently been adopted by families is that the period of that particular adversity is temporally discrete and the end date for the adversity is known. Therefore, we are able to examine the effects of timing of early-life stress on the developing emotional system. It was hypothesized that longer stays in an orphanage would be associated with atypical limbic development and associated emotion regulation difficulties, including anxiety. In general, the data from this study support this hypothesis.
We provide evidence that long periods of orphanage rearing are associated with alterations in neuroanatomical development. Specifically, children who had remained in orphanage care for the longest amount of time had amygdala volumes (cortex-corrected) that exceeded those of comparison children. These data suggest that the type of caregiving present in orphanages may act as a psychological stressor for an infant and alter the developmental trajectory of a major neuroanatomical system involved in emotion processing. What is striking about the data from the current study is that the effects of adversity are observed years after termination of the adversity, similar to what has been shown in animal models of stress and recovery (Vyas et al., 2004
). In these animal studies the hippocampus, but not the amygdala, recovers from its dendritic shrinkage, and this recovery may explain why only a non-significant trend for smaller hippocampus volume was observed in the PI group. The comparison group for the early adopted PI group was approximately one year older than the early adopted PI children. Measurable amygdala development during a year was not expected and therefore, the age difference is not concerning. Moreover, amygdala volume did not differ between the early adopted group and a comparison group that did not differ in age.
Developmental outcome for children who experience orphanage rearing is impacted by the length of time a child is there with longer stays generally associated with psychiatric disturbances (Beckett, Maughan, Rutter, Castle, Colvert, Groothues, Kreppner, Stevens, O'Connor T, & Sonuga-Barke, 2006
; Durfee, 1933
; Rutter, 1998
; Rutter et al., 2004
). The current study examined likely biological substrates that underlie these dose-related effects on emotional behavior. There is no appropriate control group for PI children since there are a number of variables that could differ between groups. Therefore, by comparing the PI group to one another with age adopted out of the orphanage as an independent variable in the regression analyses, we in part control for this variability and compare within the PI group along this influential variable. Age adopted out predicted amygdala volume in a dose-related fashion, where longer periods of orphanage rearing were related to larger amygdala volumes (cortex-corrected), a pattern which is highly consistent with the earlier described animal models that have shown a causal link between early-life stress and subsequent emotional behavior. Although Gunnar and colleagues (2007)
have shown that children adopted from Eastern Europe are at greater risk for developing behavior problems and in the current sample children from Eastern Europe tended to be adopted at older ages, the association between age adopted out and amygdala volume remained even when only children adopted from Asia were included in the analyses.
In contrast, prolonged stress typically results in a decrease in structure and function (see Bremner, 2006
and McEwen, 2007
for a review of the literature), a phenotype which shows recovery once the stressor period has ended (Vyas et al., 2004
), even when that stress is experienced early in life (Yang, Hou, Ma, Liu, Zhang, Zhou, Xu, & Li, 2007
). Similarly, in the current study, the difference in hippocampal measurements between PI and comparison children did not reach statistical significance, perhaps as a result of the overwhelming enrichment PI children typically receive in homes relative to orphanages. The lack of hippocampal and caudate differences also highlights the specific long-term association between stress and the amygdala. Alternatively, hippocampal changes following stress may be masked during childhood. Studies do not find stress-induced hippocampal shrinkage in children, although adults who experienced stress as children show decreased hippocampal volume (Bremner, Vythilingam, Vermetten, Southwick, McGlashan, Nazeer, Khan, Vaccarino, Soufer, Garg, Ng, Staib, Duncan, & Charney, 2003
). Perhaps developmental change in hippocampal volume prevents observation of stress-induced changes in hippocampus as measured by MRI. Indeed, most of the children in the current study were female, and in typical female subjects hippocampal volume tends to show developmental change during childhood and adolescence (Giedd, Vaituzis, Hamburger, Lange, Rajapakse, Kaysen, Vauss, & Rapoport, 1996
), while amygdala volumes tends to not show development change as measured by structural MRI.
We used an emotional go-nogo task to measure individual differences in one’s ability to regulate behavior during the presentation of emotionally provocative social information. As a group, all children performed better when blocks contained positive facial expressions and when emotional faces were the target stimuli rather than the distracter stimuli, as indexed by high % correct scores and fast reaction times. However, children who spent the longest amount of time in orphanage care made significantly more errors during blocks of trials that contained negatively valenced faces. The errors associated with later ages of adoption were false alarms errors when the distractor item (the item during which one was instructed to withhold pressing) was a negatively valenced face. These errors are viewed as errors in behavioral regulation (i.e., default to the prepotent response of pressing the button, which is the more frequent response) when cognitive resources were captured by emotionally salient events. The greater number of accidental responses to distracters might be the result of PI children being more affected by the emotional context of the task in general and therefore, their behavior being biased more by this information. In support of this theory, unlike with the comparison group, the amount of time needed for a PI child to press the button for targets varied greatly depending on both the valence and the stimulus type. The resulting pattern, relative slowing to neutral in the context of positive valence and relative accelerating to neutral when in the context of negatively valenced faces, is consistent with the notion that late adopted PI children are more likely than other children to be influenced by emotional contexts. This susceptibility to the emotional context is consonant with the difficulty in emotion regulation reported previously for this population of children (Hodges & Tizard, 1989
) and may be the basis for emotion regulation difficulties. These statements are made with caution since children who have experienced parental neglect have shown impairments in expression recognition (Pollak et al., 2002
), and these difficulties could contribute to poor performance in the face gonogo. However, in the current study age adopted out of an orphanage was specifically associated with false alarm errors, not misses, and this pattern of errors suggests that early institutionalization is associated with poor self regulation in the presence of emotionally arousing stimuli.
Poor emotion regulation is mediated by cellular growth in the amygdala in animal models of stress (Mitra et al., 2005
; Vyas et al., 2002
). Anxious humans (both children and adults), typically have a larger and more reactive amygdala as well as a greater processing bias for negative information (Barros-Loscertales et al., 2006
; Bradley et al., 1999
; Dalgleish et al., 2001
; Mogg, Bradley, de Bono, & Painter, 1997
; Mogg, Bradley, & Hallowell, 1994
; Mogg, Kentish, & Bradley, 1993
) and children with anxiety disorders (De Bellis et al., 2000
; MacMillan et al., 2003
). PI children tend to show more anxiety (Ellis et al., 2004
) and internalizing behavior problems relative to non-adopted peers (although still showing less than children who were domestically adopted; Juffer & van Ijzendoorn, 2005
). Therefore, understanding the development of these phenotypes provides a framework for understanding anxiety. In the current study larger amygdala volumes predicted higher ratings of anxiety (as measured by the SCARED) and more internalizing behaviors (as measured by the CBCL), which is a risk factor for later psychopathology including mood disorder (Hofstra, van der Ende, & Verhulst, 2002
). The association between internalizing/anxious behaviors and larger amygdala volume existed for both the PI group and the comparison group, suggesting that early stress may be one of many possible routes to later anxious phenotypes. There was a trend for amygdala volume to predict more difficulties in emotional regulation (greater number of errors for faces with negative valence). The number of PI children in this study who reached diagnostic threshold for an anxiety disorder exceeded those reported within the greater population (Costello, Angold, Burns, Stangl, Tweed, Erkanli, & Worthman, 1996
). Nonetheless, there were too to properly test whether the presence of an anxiety disorder was related to amygdala volume; however, the association between amygdala volume and age adopted out of the orphanage remained even when children with clinical anxiety were excluded from the analysis. While we cannot determine directionality based on these results, in the context of the animal literature, they suggest that early stress can result in amygdala hypertrophy, which produces greater reactivity to highly emotional stimuli and a more anxious phenotype. This type of adversity-driven “kindling” of the amygdala may be a significant risk factor for the development of anxiety disorders (Rosen et al., 1998
). This etiological model of anxiety is supported by previous work (Thomas et al., 2001
) showing that greater amygdala response to negative information correlates positively with everyday ratings of anxiety in children and adolescents.
Ethical constraints render it difficult to randomly assign children to rearing environments (Nelson, Zeanah, Fox, Marshall, Smyke, & Guthrie, 2007
; Zeanah, Nelson, Fox, Smyke, Marshall, Parker, & Koga, 2003
), and therefore, these data can only show a relationship between orphanage rearing and differences in emotion processing systems. There are other possible interpretations of the data. For example, longer periods in an orphanage translates into shorter periods with the family, and based on the high socio-economic status profile of families who tend to adopt internationally (Hellerstedt et al., 2008
), presumably this is an environment that is an enriched on relative to an orphanage. So, although these data suggest that the effects of institutionalization were greatest for those children who remained in the orphanage the longest, it may instead be that amygdala volume and hypersensitivity to negative stimuli decrease with increasing amounts of time spent with a family. In this way, time with family can be viewed as an “intervention” for children who have experienced orphanage rearing. Although data from animal models suggest that changes in amygdala morphology are resistant to recovery (Vyas, Pillai, & Chattarji, 2004
), longitudinal data will establish whether these data reflect actual plasticity and eventual normalization in emotion processing systems.
There are a number of limitations of this study inherent to research on this special population. First, the current nature of international adoption is such that parents, and thus researchers, do not have access to preadoption developmental histories, and there are many levels of privation. Given the heterogeneity of this sample, it would be impossible to define an appropriate control group for PI children. The approach taken in this paper, to rely on the continuous variable of age of adoption, has merit in that we are able to compare children within groups and make claims about the duration for which the adversity was experienced. We see this approach as a promising one for future studies with this population, and recognize that the comparison against non-adopted healthy children may be too liberal. Such comparisons are, however, informative when trying to understand how PI children may deviate from typical progressions of behavior and brain development. Because of the correlational nature of this study, it is also possible that children who are psychiatrically healthier may be more likely to be adopted out of the orphanage at earlier ages. Thirdly, although the adoption process itself may be a temporary stressor, it is a constant across the PI group, and our measures were taken years after the adoption process. Therefore, it is our opinion that the observed effects were the effects of institutionalization, not the adoption process itself. Fourth, although neuroimaging data are presented from 62 children and behavioral data are presented from 46 children, only 30 children provided complete neuroimaging and behavioral data. There remains the possibility that the children who provided neuroimaging but not behavioral data and children who provided behavioral data but not neuroimaging data are different from each other and therefore, should not be grouped together in discussion of long-term correlates of early institutionalization. Although the general pattern of increased emotionality remains consistent across all subgroups of PI children who participated in this study, conclusions about the consistency between emotional behavior and amygdala findings based on these results should be tempered. One of the goals of this study was to examine the development of limbic structures and associated behaviors following early institutional care. While this question is best addressed using a longitudinal design, the current design was cross-sectional, which tempers the strength of the conclusions that can be drawn form the data.
A final question that remains unanswered regards the age at which the adversity was experienced. Age adopted out of the orphanage predicted amygdala volume and performance on the emotional go-nogo task. It is not clear whether these effects were caused by the duration of time spent in the orphanage or the chronological age at which children experienced the stressor. Data from non-human primates that vary the age of maternal separation suggest that the experiences of later maternally-separated youngsters and the mourning they endure are fundamentally different from those who are separated soon after birth (Nelson et al., 2002
). We are unable to ask this developmental question with the current design.
What does a larger amygdala indicate on a functional level? The literature from animal models suggests that amygdala hypertrophy is associated with increased reactivity (Vyas, Jadhav, & Chattarji, 2006
), consistent with the behavioral and clinical data presented in this manuscript. Decreased activity in limbic regions, including the amygdala, has been reported elsewhere (Chugani, Behen, Muzik, Juhasz, Nagy, & Chugani, 2001
), although the comparison groups used in that study (adults and epileptic children) make the results difficult to interpret. To better understand the functional significance of enlarged amygdala volumes found in this population, future work will need to examine amygdala activity to emotionally provocative stimuli in this population using such techniques as functional MRI.
Much has been learned from animal models about the effects of stress on emotional behavioral and underlying neural circuitry. Because pre- and post-adoption environments differ to a great extent, studying children who have experienced orphanage rearing provides an opportunity to examine how early adversity can impact the developing emotional system in ways that are difficult to do in other stressed populations, where the effects of early and later stress cannot be easily untangled. Importantly, such studies also provide information on how and whether these systems can be altered or normalized to a typical developmental trajectory. The dose related finding directly informs policymaking by underscoring the importance of a rapid adoption process. Data like those presented in this paper should inform parents, therapists, pediatricians, agencies, and policy makers to minimize orphanage rearing experiences worldwide.