Telomere Erosion and Depressive Symptoms Across Development Following Institutional Care.

OBJECTIVE: A large literature has identified exposure to early caregiving adversities as a potent risk for developing affective psychopathology, with depression, in particular, increasing across childhood into adolescence. Evidence suggests telomere erosion, a marker of biological aging, may underlie associations between adverse early-life experiences and later depressive behavior; yet, little is understood about this association during development. METHOD: The current accelerated longitudinal study examined concurrent telomere length and depressive symptoms concurrently, 2 and 4 years later, from the preschool period through adolescence among children exposed (n =116) and not exposed (n = 242) to early previous institutional (PI) care. RESULTS: PI care was associated with shorter telomeres on average and with quadratic age-related growth in depressive symptoms, indicating a steeper association between PI care and depressive symptoms in younger age groups that leveled off in adolescence. Contrary to studies in adult samples, telomere length was not associated with depressive symptoms, and it did not predict future symptoms. CONCLUSION: These findings indicate that early caregiving disruptions increase the risk for both accelerated biological aging and depressive symptoms, although these variables did not correlate with each other during this age range.

Age-related change in task-evoked amygdala-prefrontal circuitry: A multiverse approach with an accelerated longitudinal cohort aged 4-22 years.

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed - perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala-mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years-old; N = 98; 183 scans; 1-3 scans/participant). Participants recruited from the greater Los Angeles area completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala-mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala-mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala-mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results.

Longitudinal changes in amygdala, hippocampus and cortisol development following early caregiving adversity.

Although decades of research have shown associations between early caregiving adversity, stress physiology and limbic brain volume (e.g., amygdala, hippocampus), the developmental trajectories of these phenotypes are not well characterized. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4-20 years old) completed 1-3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239) and structural MRI (N = 156). We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth rate of the amygdala, resulting in smaller volumes by adolescence. Amygdala and hippocampal volumes were also prospectively associated with future morning cortisol in both groups. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood.

Mind and gut: Associations between mood and gastrointestinal distress in children exposed to adversity.

Gastrointestinal and mental disorders are highly comorbid, and animal models have shown that both can be caused by early adversity (e.g., parental deprivation). Interactions between the brain and bacteria that live within the gastrointestinal system (the microbiome) underlie adversity-gastrointestinal-anxiety interactions, but these links have not been investigated during human development. In this study, we utilized data from a population of 344 youth (3-18 years old) who were raised with their biological parents or were exposed to early adverse caregiving experiences (i.e., institutional or foster care followed by international adoption) to explore adversity-gastrointestinal-anxiety associations. In Study 1, we demonstrated that previous adverse care experiences were associated with increased incidence of gastrointestinal symptoms in youth. Gastrointestinal symptoms were also associated with concurrent and future anxiety (measured across 5 years), and those gastrointestinal symptoms mediated the adversity-anxiety association at Time 1. In a subsample of children who provided both stool samples and functional magnetic resonance imaging of the brain (Study 2, which was a "proof-of-principle"), adversity was associated with changes in diversity (both alpha and beta) of microbial communities, and bacteria levels (adversity-associated and adversity-independent) were correlated with prefrontal cortex activation to emotional faces. Implications of these data for supporting youth mental health are discussed.

Parental presence switches avoidance to attraction learning in children.

Attachment-related learning (that is, forming preferences for cues associated with the parent) defies the traditional rules of learning in that it seems to occur independently of apparent reinforcement1-young children prefer cues associated with their parent, regardless of valence (rewarding or aversive), despite the diversity of parenting styles2. This obligatory attraction for parental cues keeps the child nearby and safe to explore the environment; thus, it is critical for survival and sets the foundation for normal human cognitive-emotional behaviour. Here we examined the learning underlying this attraction in preschool-age children. Young children underwent an aversive conditioning procedure either in the parent's presence or alone. We showed that despite disliking the aversive unconditioned stimulus, children exhibited a behavioural approach for conditioned stimuli that were acquired in the parent's presence and an avoidance for stimuli acquired in the parent's absence, an effect that was strongest among those with the lowest cortisol levels. The results suggest that learning systems during early childhood are constructed to permit modification by parental presence.

Working memory moderates the association between early institutional care and separation anxiety symptoms in late childhood and adolescence.

Adverse caregiving, for example, previous institutionalization (PI), is often associated with emotion dysregulation that increases anxiety risk. However, the concept of developmental multifinality predicts heterogeneity in anxiety outcomes. Despite this well-known heterogeneity, more work is needed to identify sources of this heterogeneity and how these sources interact with environmental risk to influence mental health. Here, working memory (WM) was examined during late childhood/adolescence as an intra-individual factor to mitigate the risk for separation anxiety, which is particularly susceptible to caregiving adversities. A modified "object-in-place" task was administered to 110 youths (10-17 years old), with or without a history of PI. The PI youths had elevated separation anxiety scores, which were anticorrelated with morning cortisol levels, yet there were no group differences in WM. PI youths showed significant heterogeneity in separation anxiety symptoms and morning cortisol levels, and WM moderated the link between caregiving and separation anxiety and mediated the association between separation anxiety and morning cortisol in PI youth. Findings suggest that (a) institutional care exerts divergent developmental consequences on separation anxiety versus WM, (b) WM interacts with adversity-related emotion dysregulation, and (c) WM may be a therapeutic target for separation anxiety following early caregiving adversity.

Decreased Amygdala Reactivity to Parent Cues Protects Against Anxiety Following Early Adversity: An Examination Across 3 Years.

BACKGROUND: The human brain remains highly plastic for a protracted developmental period. Thus, although early caregiving adversities that alter amygdala development can result in enduring emotion regulation difficulties, these trajectories should respond to subsequent enriched caregiving. Exposure to high-quality parenting can regulate (i.e., decrease) children's amygdala reactivity, a process that, over the long term, is hypothesized to enhance emotion regulation. We tested the hypothesis that even following adversity, the parent-child relationship would be associated with decreases in amygdala reactivity to parent cues, which would in turn predict lower future anxiety. METHODS: Participants were 102 children (6-10 years of age) and adolescents (11-17 years of age), for whom data were collected at one or two time points and who either had experienced institutional care before adoption (n = 45) or had lived always with their biological parents (comparison; n = 57). We examined how amygdala reactivity to visual cues of the parent at time 1 predicted longitudinal change (from time 1 to time 2) in parent-reported child anxiety across 3 years. RESULTS: At time 1, on average, amygdala reactivity decrements to parent cues were not seen in children who had received institutional care but were seen in children in the comparison group. However, some children who previously experienced institutional care did show decreased amygdala reactivity to parent cues (∼40%), which was associated with greater child-reported feelings of security with their parent. Amygdala decreases at time 1 were followed by steeper anxiety reductions from time 1 to time 2 (i.e., 3 years). CONCLUSIONS: These data provide a neurobiological mechanism by which the parent-child relationship can increase resilience, even in children at significant risk for anxiety symptoms.

Positive valence bias and parent-child relationship security moderate the association between early institutional caregiving and internalizing symptoms.

Institutional caregiving is associated with significant deviations from species-expected caregiving, altering the normative sequence of attachment formation and placing children at risk for long-term emotional difficulties. However, little is known about factors that can promote resilience following early institutional caregiving. In the current study, we investigated how adaptations in affective processing (i.e., positive valence bias) and family-level protective factors (i.e., secure parent-child relationships) moderate risk for internalizing symptoms in previously institutionalized (PI) youth. Children and adolescents with and without a history of institutional care performed a laboratory-based affective processing task and self-reported measures of parent-child relationship security. PI youth were more likely than comparison youth to show positive valence biases when interpreting ambiguous facial expressions. Both positive valence bias and parent-child relationship security moderated the association between institutional care and parent-reported internalizing symptoms, such that greater positive valence bias and more secure parent-child relationships predicted fewer symptoms in PI youth. However, when both factors were tested concurrently, parent-child relationship security more strongly moderated the link between PI status and internalizing symptoms. These findings suggest that both individual-level adaptations in affective processing and family-level factors of secure parent-child relationships may ameliorate risk for internalizing psychopathology following early institutional caregiving.

Diurnal cortisol after early institutional care-Age matters.

Several studies have shown that young children who have experienced early caregiving adversity (e.g. previously institutionalization (PI)) exhibit flattened diurnal cortisol slopes; however, less is known about how these patterns might differ between children and adolescents, since the transition between childhood and adolescence is a time of purported plasticity in the hypothalamic-pituitary-adrenal (HPA) axis. PI youth experience a massive improvement in caregiving environment once adopted into families; therefore we anticipated that a developmental increase in HPA axis plasticity during adolescence might additionally allow for an enhanced enrichment effect by the adoptive family. In a cross-sectional sample of 197 youths (PI and Comparison; 4-15 years old) we observed age-related group differences in diurnal slope. First replicating previous findings, PI children exhibited flattened diurnal slope. This group difference, however, was not observed in adolescents. Moderation analyses showed that pubertal development, increased time with family, and early adoption contributed to the steeper diurnal cortisol slope in PI adolescents. These findings add support to existing theories positing that the transition between middle childhood and adolescence may mark an additional sensitive period for diurnal cortisol patterning, allowing PI youth to benefit from the enriched environment provided by adoptive parents during this period of development.

Maternal buffering of human amygdala-prefrontal circuitry during childhood but not during adolescence.

Mature amygdala-prefrontal circuitry regulates affect in adulthood but shows protracted development. In altricial and semialtricial species, caregivers provide potent affect regulation when mature neurocircuitry is absent. The present investigation examined a potential mechanism through which caregivers provide regulatory influences in childhood. Children, but not adolescents, showed evidence of maternal buffering, such that maternal stimuli suppressed amygdala reactivity. In the absence of maternal stimuli, children exhibited immature amygdala-prefrontal connectivity. However, in the presence of maternal stimuli, children's connectivity was more mature, resembling adolescents' connectivity. Children showed improved affect-related regulation in the presence of their mothers. Individual differences emerged, with greater maternal influence on amygdala-prefrontal circuitry associated with stronger mother-child relationships and maternal modulation of behavioral regulation. These findings suggest a neural mechanism through which caregivers modulate children's regulatory behavior by inducing more mature connectivity and buffering against heightened reactivity. Maternal buffering in childhood, but not adolescence, suggests that childhood may be a sensitive period for amygdala-prefrontal development.

Early experience shapes amygdala sensitivity to race: an international adoption design.

In the current study, we investigated how complete infant deprivation to out-group race impacts behavioral and neural sensitivity to race. Although monkey models have successfully achieved complete face deprivation in early life, this is typically impossible in human studies. We overcame this barrier by examining youths with exclusively homogenous racial experience in early postnatal development. These were youths raised in orphanage care in either East Asia or Eastern Europe as infants and later adopted by American families. The use of international adoption bolsters confidence of infant exposure to race (e.g., to solely Asian faces or European faces). Participants completed an emotional matching task during functional MRI. Our findings show that deprivation to other-race faces in infancy disrupts recognition of emotion and results in heightened amygdala response to out-group faces. Greater early deprivation (i.e., later age of adoption) is associated with greater biases to race. These data demonstrate how early social deprivation to race shapes amygdala function later in life and provides support that early postnatal development may represent a sensitive period for race perception.

Indiscriminate amygdala response to mothers and strangers after early maternal deprivation.

BACKGROUND: In altricial species, maternal stimuli have powerful effects on amygdala development and attachment-related behaviors. In humans, maternal deprivation has been associated with both "indiscriminate friendliness" toward non-caregiving adults and altered amygdala development. We hypothesized that maternal deprivation would be associated with reduced amygdala discrimination between mothers and strangers and increased parent report of indiscriminate friendliness behaviors. METHODS: Sixty-seven youths (33 previously institutionalized; 34 comparison; age-at-scan 4-17 years) participated in a functional magnetic resonance imaging experiment designed to examine amygdala response to mother versus stranger faces. In-scanner behavior was measured. Indiscriminate friendliness was assessed with parental report. RESULTS: Comparison youth showed an amygdala response that clearly discriminated mother versus stranger stimuli. Previously institutionalized youths, by contrast, exhibited reduced amygdala discrimination between mothers and strangers. Reduced amygdala differentiation correlated with greater reports of indiscriminate friendliness. These effects correlated with age-at-adoption, with later adoptions being associated with reduced amygdala discrimination and more indiscriminate friendliness. CONCLUSIONS: Our results suggest that early maternal deprivation is associated with reduced amygdala discrimination between mothers and strangers, and reduced amygdala discrimination was associated with greater reports of indiscriminate friendliness. Moreover, these effects increased with age-at-adoption. These data suggest that the amygdala, in part, is associated with indiscriminate friendliness and that there might be a dose-response relationship between institutional rearing and indiscriminate friendliness.

A developmental shift from positive to negative connectivity in human amygdala-prefrontal circuitry.

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. Although tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4-22 years using task-based functional magnetic resonance imaging. Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-medial prefrontal cortex functional connectivity was significantly positive (greater than zero) among participants younger than 10 years, whereas functional connectivity was significantly negative (less than zero) among participants 10 years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.

Amygdala sensitivity to race is not present in childhood but emerges over adolescence.

Neuroimaging research in adults has consistently found that differential perception of race is associated with increased amygdala activity. We hypothesized that such neural biases unlikely reflect innate processes but instead emerge over development. In the current study, we used fMRI to examine the neurodevelopmental trajectory of the amygdala in response to race across childhood and adolescence ranging from 4 to 16 years. Thirty-two youths viewed African American and European American faces during a functional brain scan. Results suggest that differential amygdala response to African American faces does not emerge until adolescence, reflecting the increasing salience of race across development. In addition, greater peer diversity was associated with attenuated amygdala response to African American faces, suggesting that intergroup racial contact may reduce the salience of race.

Amygdala response to mother.

In altricial species, like the human, the caregiver, very often the mother, is one of the most potent stimuli during development. The distinction between mothers and other adults is learned early in life and results in numerous behaviors in the child, most notably mother-approach and stranger wariness. The current study examined the influence of the maternal stimulus on amygdala activity and related circuitry in 25 developing children (n = 13) and adolescents (n = 12), and how this circuitry was associated with attachment-related behaviors. Results indicated that maternal stimuli were especially effective in recruiting activity in the left dorsal amygdala, and activity in this amygdala region showed increased functional connectivity with evaluative and motor regions during viewing of maternal stimuli. Increases in this left dorsal amygdala activity and related amygdala-cortical functional connectivity were associated with increased mother-approach behaviors as measured by in-scanner behavioral responding and out-of-scanner child-report. Moreover, age-related changes in amygdala activity to strangers statistically mediated the developmentally typical decline in stranger wariness seen across this period. These results suggest that mother-induced behaviors are enacted by maternal influence on amygdala-cortical circuitry during childhood and adolescence.

Construct validity of the Miller assessment for preschoolers and the pediatric examination of educational readiness for children.

The purpose of this study was to investigate the construct validity of the Miller Assessment for Preschoolers (MAP) and the Pediatric Examination of Educational Readiness (PEER), two assessment tools that occupational therapists and physical therapists can use for early identification of children with developmental disabilities. The sample included 84 Israeli children who were tested on the MAP (42 children with pre-academic problems and 42 typically developing children), and 70 children who were tested on the PEER (35 children with pre-academic problems and 35 typically developing children). Out of this pool of subjects, 30 typically developing children and 30 children with pre-academic problems were tested on both tests and the results were used for additional data analysis. We found differences between the groups' MAP and PEER total scores as well as their developmental indices scores. Children with pre-academic problems scored lower. The supplementary behavioral observations of the tests yielded less definite results. A strong correlation existed between the total scores of the MAP and the PEER, and the total scores of the tests correlated significantly with each of the sub-scores of the other test. The findings support the construct validity of both tests, thereby suggesting that either test can be used to identify children with pre-academic problems.