Editorial: Placing research in context - what participant and study characteristics should be routinely reported in studies of child and adolescent mental health?

This editorial argues that research findings in child and adolescent psychopathology need to be contextualized with demographic information and location in order to help with interpretation of findings and implications for the services that are available and/or potentially effective. For developmental psychopathology and child and adolescent mental health treatment, the demographic information should include key factors known to influence etiology, treatment effectiveness and service availability. These factors include, but may not be limited to, sex and age, location including country (and city or urban area), socioeconomic class, culture and minoritized status. Including such information, in addition to helping us understand why findings might not generalize, can draw attention to the exclusion of certain groups from research and so drive attempts to increase the representativeness of research in child and adolescent mental health.

Impacts of early deprivation on behavioral and neural measures of executive function in early adolescence.

Children reared in institutional settings experience early deprivation that has lasting implications for multiple aspects of neurocognitive functioning, including executive function (EF). Changes in brain development are thought to contribute to these persistent EF challenges, but little research has used fMRI to investigate EF-related brain activity in children with a history of early deprivation. This study examined behavioral and neural data from a response conflict task in 12-14-year-olds who spent varying lengths of time in institutional care prior to adoption (N = 84; age at adoption - mean: 15.85 months, median: 12 months, range: 4-60 months). In initial analyses, earlier- and later-adopted (EA, LA) youth were compared to a group of children raised in their biological families (non-adopted, NA). NA youth performed significantly more accurately than LA youth, with EA youth falling in between. Imaging data suggested that previously institutionalized (PI) youth activated additional frontoparietal regions, including dorsolateral prefrontal cortex, as compared to NA youth. In addition, EA youth uniquely activated medial prefrontal regions, and LA uniquely activated parietal regions during this task. A separate analysis in a larger group of PI youth examined whether behavioral or brain measures of EF varied with the duration of deprivation experienced. Duration of deprivation was negatively associated with activation of default mode network (DMN) regions. Overall, results suggest that there are lasting effects of deprivation on EF, but that those who are removed from institutional care earlier may be able to recruit additional neural resources as a compensatory mechanism.

Post-adoption experiences of discrimination moderated by sleep quality are associated with depressive symptoms in previously institutionalized youth over and above deprivation-induced depression risk.

The association of post-adoption experiences of discrimination with depressive symptoms was examined in 93 previously institutionalized (PI) youth (84% transracially adopted). Additionally, we explored whether sleep quality statistically moderated this association. Notably, we examined these associations after covarying a measure of autonomic balance (high/low frequency ratio in heart rate variability) affected by early institutional deprivation and a known risk factor for depression. PI youth exhibited more depressive symptoms and experiences of discrimination than 95 comparison youth (non-adopted, NA) raised in their biological families in the United States. In the final regression model, there was a significant interaction between sleep quality and discrimination, such that at higher levels of sleep quality, the association between discrimination and depression symptoms was non-significant. Despite being cross-sectional, the results suggest that the risk of depression in PI youth involves post-adoption experiences that appear unrelated to the impacts of early deprivation on neurobiological processes associated with depression risk. It may be crucial to examine methods of improving sleep quality and socializing PI youth to cope with discrimination as protection against discrimination and microaggressions.

Household Income, Cortisol, and Obesity During Early Childhood: A Prospective Longitudinal Study.

OBJECTIVE: To prospectively evaluate the relationship between household income, children's cortisol, and body mass index (BMI) trajectories over a 3-year period in early childhood. STUDY DESIGN: Household income, child hair cortisol levels, and BMI were measured at baseline, 12-, 24-, and 36-month follow-up visits in the Now Everybody Together for Amazing and Healthful Kids (NET-Works) Study (n = 534, children ages 2-4 years, and household income <$65 000/year at baseline). Relationships were examined between very low household income (<$25 000/year) at baseline, income status over time (remained <$25 000/year or had increasing income), cortisol accumulation from hair samples, and BMI percent of the 95th percentile (BMIp95) trajectories using adjusted linear growth curve modeling. Households with baseline income between $25 000 and $65 000/year were the reference group for all analyses. RESULTS: Children from very low-income households at baseline had annual changes in BMIp95 that were higher (P < .001) than children from reference group households (0.40 vs -0.62 percentage units/year). Annual increases in BMIp95 were also greater among children from households that remained very low income (P < .01, .34 percentage units/year) and among those with increasing income (P = .01, .51 percentage units/year) compared with the reference group (-0.61 percentage units/year). Children from households that remained very low income had higher hair cortisol accumulations (0.22 pg/mg, P = .02) than reference group children, whereas hair cortisol concentrations of children from households with increasing income (0.03 pg/mg) did not differ significantly from the reference group. Cortisol was not related to BMIp95. CONCLUSIONS: The economic circumstances of families may impact children's BMI trajectories and their developing stress systems, but these processes may be independent of one another.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

Editorial: Using parenting interventions as treatments and brain development - are we at the end of the beginning yet?

This editorial discusses where we stand in understanding how parenting interventions, frequently used in the treatment of child emotional and behavioral disorders, affect the brain systems that contribute to these disorders. It concludes that although we have some evidence from RCTs that improving adverse parenting causally impacts some aspects of brain development, there is almost nothing examining parenting randomized controlled trials to treat child clinical disorders and effects on brain structure or function. It argues that if we are to be a brain science, such studies are needed.

Is economic hardship associated with young children's cortisol levels?

Economic hardship during childhood has been linked to poor physical and mental health. This study examines cross-sectional and longitudinal associations of a summed economic hardship score of poverty, food insecurity, and financial hardship with hair cortisol in young children. Data from 24-month (Time 1, mean age 5 years) and 36-month (Time 2, mean age 6 years) follow-up from the NET-Works obesity prevention trial (NET-Works, NCT0166891) were used. Hair cortisol measures obtained at each time point were log-transformed and regressed on economic hardship at Time 1 and a cumulative economic hardship from Time 1 to Time 2, using generalized linear regressions. All models were adjusted for child age, sex, race/ethnicity, and intervention (prevention vs. control) arm. The final analytic sample sizes ranged from 248 to 287. Longitudinal analyses indicated that for every 1-unit higher economic hardship score at Time 1, hair cortisol at Time 2 follow-up was on average 0.07 log-picograms per milligram (pg/mg) higher (95% confidence interval [CI]: 0.01, 0.13). For every 1-unit increase in the cumulative economic hardship score between Time 1 and 2, there was a 0.04 log-pg/mg (95% CI: 0.00, 0.07) average higher level of hair cortisol at Time 2 follow-up. Results show suggestive but limited evidence for an association between economic hardship and cortisol in young children.

Does rapid rebound height growth come at a neurocognitive cost for previously institutionalized youth?

BACKGROUND: Height growth faltering is associated with less optimal behavioral outcomes and educational achievement. Although catch-up growth after growth delay may result in developmental gains, it may also present as a double-edged sword, with consequences for neurocognitive functioning such as symptoms of inattention and hyperactivity. As previously institutionalized (PI) children experience height delays at adoption and catch-up growth after adoption, they provide a cohort to test associations between catch-up growth and attention deficit hyperactivity disorder (ADHD) symptoms. METHODS: This study used latent growth curve modeling to examine how catch-up in height-for-age growth is related to attention problems in a population of PI youth followed from adoption in infancy through kindergarten. Participants were assessed within three months of arrival into their families (age at entry: 18-36 months). Anthropometrics were measured four times, approximately 7 months apart. Two visits measured behavioral outcomes with parent and teacher reports of ADHD, internalizing, and externalizing symptoms at age 5 and kindergarten. RESULTS: The slope of growth in height z-scores, but not the intercept, was positively associated with parent- and teacher-reported ADHD symptoms in children. A one standard deviation increase in the slope of height z-scores across four assessments was associated with a 0.252 standard deviation increase in ADHD symptoms after controlling for internalizing and externalizing problems, iron status, duration of institutional care, sex, and age. The slope of growth was also associated with internalizing but not externalizing symptoms. CONCLUSIONS: This study demonstrates that PI children exhibit individual trajectories of height growth postadoption. Higher rates of change in height-for-age growth were associated with increased ADHD symptoms. These results suggest that catch-up growth comes 'at the cost' of poor attention regulation and hyperactive behavior.

Pubertal stress recalibration reverses the effects of early life stress in postinstitutionalized children.

Nonhuman animal models reveal that the hypothalamic-pituitary-adrenocortical (HPA) axis calibrates to the harshness of the environment during a sensitive period in infancy. Humans exposed to depriving institutional care in infancy show reduced HPA axis responsivity, even years after they are placed in supportive, well-resourced families. This study examined whether puberty opens a window of opportunity to recalibrate the HPA axis toward more typical reactivity when children shift from harsh deprived conditions in infancy into supportive conditions in childhood and adolescence. Participants (n = 129 postinstitutionalized, 68.2% female; n = 170 comparison, 52.4% female) completed 3 annual sessions beginning at ages 7 to 15 (M = 11.28, SD = 2.31). Each session assessed pubertal stage via nurse examination and cortisol reactivity to the Trier social stress test for children. The linear mixed-effects model controlling for sex and between-individual differences in pubertal stage showed a significant group by pubertal stage interaction: within-individual increases in pubertal stage were associated with increases in cortisol stress reactivity for postinstitutionalized youth but not nonadopted comparison youth. This study indicates that pubertal development reopens a window of opportunity for the HPA axis to recalibrate based on significant improvements in the supportiveness of the environment relative to that in infancy. The peripubertal period may be an important time in development where the caregiving environment has a substantial impact on the HPA axis and, perhaps, other stress-mediating systems. Future research is needed to examine the mechanisms of recalibration and whether HPA recalibration impacts physical and psychological health.

Early-life stress and current stress predict BMI and height growth trajectories in puberty.

In cross-sectional analyses, early institutional care is associated with shorter stature but not obesity during puberty in children adopted into US families. We examined whether shorter stature and leaner body composition in youth adopted internationally from institutions would continue as puberty progressed. We also examined whether current psychosocial stress would moderate the association between early institutional deprivation and growth during adolescence. Using an accelerated longitudinal design and linear mixed-effects models, we examined the height and body mass index (BMI) of 132 previously institutionalized (PI) and 176 nonadopted (NA) youth. We examined youth aged 7-15 at the beginning of the study three times across 2 years. Nurses assessed anthropometrics and pubertal status. Current psychosocial stress was measured using the Youth Life Stress Interview. Our results indicated that PI youth remained shorter and leaner across three assessments than NA youth. However, age-and-sex-adjusted BMI increased faster in PI youth. Psychosocial stress during puberty predicted greater age-and-sex-adjusted BMI, but this effect did not differ by group. The gap in BMI but not height appears to close between PI and NA youth. Higher psychosocial stress was associated with higher BMI during puberty.

Life stress and cortisol reactivity: An exploratory analysis of the effects of stress exposure across life on HPA-axis functioning.

Stressful experiences affect biological stress systems, such as the hypothalamic-pituitary-adrenal (HPA) axis. Life stress can potentially alter regulation of the HPA axis and has been associated with poorer physical and mental health. Little, however, is known about the relative influence of stressors that are encountered at different developmental periods on acute stress reactions in adulthood. In this study, we explored three models of the influence of stress exposure on cortisol reactivity to a modified version of the Trier Social Stress Test (TSST) by leveraging 37 years of longitudinal data in a high-risk birth cohort (N = 112). The cumulative stress model suggests that accumulated stress across the lifespan leads to dysregulated reactivity, whereas the biological embedding model implicates early childhood as a critical period. The sensitization model assumes that dysregulation should only occur when stress is high in both early childhood and concurrently. All of the models predicted altered reactivity, but do not anticipate its exact form. We found support for both cumulative and biological embedding effects. However, when pitted against each other, early life stress predicted more blunted cortisol responses at age 37 over and above cumulative life stress. Additional analyses revealed that stress exposure in middle childhood also predicted more blunted cortisol reactivity.

Examining the role of socioeconomic status and temperament in the hair cortisol levels of infants.

Socioeconomic status (SES) appears to be an important contextual factor in children's developmental outcomes, including their responses to stress. However, some children are more susceptible to its effects than others. Hair cortisol is a newer method of assessing the activity of the HPA axis, providing cumulative cortisol levels. The present article examined whether temperament (negative emotionality) moderates the association between an SES index and the hair cortisol concentration (HCC) of infants. Sixty infants from 6 to 15 months of age were recruited, of which 49 had sufficient hair for cortisol analysis. The SES index was calculated from the education levels of the mothers, family income, and a scale measuring the quality of the home environment. Negative emotionality was measured with the three sub-scales of the Infant Behavior Questionnaire (falling reactivity, distress to limitations, and fear). Among infants low in negative emotionality, there was no association between SES and cortisol. In contrast, among those high in negative emotionality, a significant association was obtained. These infants showed lower levels of HCC in lower-SES environments. The findings suggest that there are individual differences in reacting to the environment, and low levels of cortisol (not high) were found in susceptible infants in lower-SES families.

Parental emotional support and social buffering in previously institutionalized and typically developing children and adolescents.

The current study tested the hypothesis that variation in parental emotional support explains differences in cortisol reactivity among 159 youth, including both previously institutionalized (PI; N = 78) and non-adopted (NA; N = 81) children (ages 9-10) and adolescents (ages 15-16). Youth participated in a Modified Trier Social Stress Test after a period of preparation with either their parent or a supportive stranger. Saliva samples were collected to derive a measure of cortisol reactivity. Our findings revealed that parents buffered the cortisol stress response for PI children and adolescents only if they were high on emotional support. Our results also suggest that simply preparing with a parent might buffer the stress response for NA children; for NA adolescents, however, only emotionally supportive parents significantly buffered their adolescents' stress.

Pubertal transition with current life stress and support alters longitudinal diurnal cortisol patterns in adolescents exposed to early life adversity.

Current and early life stress (ELS) are associated with diurnal cortisol patterns, which themselves are associated with mental and physical health. The pubertal recalibration hypothesis suggests that the social environment can impact dysregulated cortisol patterns for previously ELS-exposed youth as they transition through puberty. This study examined longitudinal change in cortisol awakening response (CAR) and diurnal slope (DS) across puberty as a function of ELS in infancy, current stress, and social support (N = 290, 7-17 years). The CAR and DS were examined thrice annually with an accelerated longitudinal design with nurse-assessed puberty to assess associations between diurnal cortisol and pubertal recalibration with ELS and the current social environment. Exposure to ELS was associated with less steep DS but not changes in CAR, and no evidence of pubertal calibration was found. The DS became less steep for youth in later pubertal stages and as youth progressed through puberty. The CAR was steeper for youth in later pubertal stages. Across the cohort, current life stress and support were associated with changes in the DS and the CAR through the pubertal transition. The pubertal stage and the peripubertal and pubertal social environment may have important implications for adrenocortical functioning with or without exposure to ELS.

Microbiota-immune alterations in adolescents following early life adversity: A proof of concept study.

Early adverse care has long-term impacts on physical and mental health. The influence of rearing conditions on the infant's gut microbiota and its relationship with developmental health has become more evident. The microbiome is essential for normal growth and metabolism, and the signaling from the gut to the brain may underlie individual differences in resilience later in life. Microbial diversity and composition were determined using 16S rRNA gene amplicon sequencing in fecal samples from 17 adolescents adopted internationally from orphanages into the United States and 18 adolescents reared in birth families who had similar educational and income levels. Analyses focused on diversity of the microbial community structure and differences in the abundance of specific bacterial taxa. Blood samples were used to immunophenotype the numbers of several T-cell subsets and cytomegalovirus (CMV) seropositivity. Negative binomial regression analysis revealed several operational taxonomic units that were significantly different based on early rearing conditions and CMV seropositivity. There were significant associations between the relative abundance of certain taxa, the percentages of T-cell subsets in circulation, and CMV seropositivity. These findings demonstrate a possible link between the gut microbiota and associations with immune alterations initiated by early life adversity.

Temperament moderates the effects of early deprivation on infant attention.

Institutional care has been shown to increase the risk of attention problems in children, but some children are more sensitive to their environment, both for better and for worse. With this in mind, the current study examined the moderating role of temperament (falling reactivity) between early adversity and attention skills. Six- to 15-month-old infants residing in institutions (n = 63) and infants reared by their biological families from low socioeconomic environments (n = 59) were recruited. The infants' attention skills were measured by calculating the length of time they spent looking at toys. The infants' temperaments were measured by a subscale of the Infant Behavior Questionnaire (falling reactivity/rate of recovery from distress). The findings were in line with the differential susceptibility theory. Compared to infants with high levels of falling reactivity, infants with lower levels of falling reactivity had better attention skills if they were in a family group, but they had lower attention skills if they were residing in institutions. The attention skills of the infants who had higher scores for falling reactivity did not appear to be affected by the adverse environment.

Infants' abilities to respond to cues for joint attention vary by family socioeconomic status.

The influence of socioeconomic variability on language and cognitive development is present from toddlerhood to adolescence and calls for investigating its earliest manifestation. Response to joint attention (RJA) abilities constitute a foundational developmental milestone that are associated with future language, cognitive, and social skills. How aspects of the family home environment shape RJA skills is relatively unknown. We investigated associations between family socioeconomic status (SES) -both parent education and family percentage of the federal poverty level (FPL)- parent depressive and anxiety symptoms and infant RJA performance in a cross-sectional sample of 173 infants aged 8-18 months and their parents from a variety of socioeconomic backgrounds. Results suggest that, correcting for age and receptive language, infants in families with greater economic resources respond to relatively less redundant, more sophisticated cues for joint attention. Although parent depressive and anxiety symptoms are negatively correlated with SES, parent depressive and anxiety symptoms were not associated with infant RJA. These findings provide evidence of SES-related differences in social cognitive development as early as infancy, calling on policymakers to address the inequities in the current socioeconomic landscape of the United States.

Early life stress and brain function: Activity and connectivity associated with processing emotion and reward.

Investigating the developmental sequelae of early life stress has provided researchers the opportunity to examine adaptive responses to extreme environments. A large body of work has established mechanisms by which the stressful experiences of childhood poverty, maltreatment, and institutional care can impact the brain and the distributed stress systems of the body. These mechanisms are reviewed briefly to lay the foundation upon which the current neuroimaging literature has been built. More recently, developmental cognitive neuroscientists have identified a number of the effects of early adversity, including differential behavior and brain function. Among the most consistent of these findings are differences in the processing of emotion and reward-related information. The neural correlates of emotion processing, particularly frontolimbic functional connectivity, have been well studied in early life stress samples with results indicating accelerated maturation following early adversity. Reward processing has received less attention, but here the evidence suggests a deficit in reward sensitivity. It is as yet unknown whether the accelerated maturation of emotion-regulation circuits comes at the cost of delayed development in other systems, most notably the reward system. This review addresses the early life stress neuroimaging literature that has investigated emotion and reward processing, identifying important next steps in the study of brain function following adversity.

Pubertal recalibration of cortisol-DHEA coupling in previously-institutionalized children.

As a period of heightened plasticity, puberty may provide a window of opportunity for recalibration of the hypothalamic-pituitary-adrenal (HPA) axis to current conditions. Our group has recently documented evidence for pubertal recalibration of HPA axis reactivity among children internationally adopted as infants from institutions into supportive, well-resourced homes. As a first step at examining potential mechanisms by which puberty may facilitate recalibration of the HPA axis, the current study assessed whether previously-institutionalized (PI) children differed from non-adopted (NA) comparison children in levels of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and in its intra-individual covariation (coupling) with cortisol by adrenal pubertal stage. In an accelerated longitudinal design, 7- to 15-year-olds completed up to 3 annual assessments, which included nurse-conducted pubertal staging and the Modified Trier Social Stress Test for Children (TSST-M). Adrenal (pubic hair) rather than gonadal pubertal stage scores were used in the analysis. Paired salivary cortisol-DHEA samples were available at 60-80 min post-TSST-M. NA and PI children did not differ in DHEA levels, which were higher among children at more advanced pubertal stages (averaged across the sessions) for both groups. For NA children, post-stressor cortisol and DHEA were positively coupled across sessions at all average adrenal pubertal stages. For PI children who were, on average, at earlier adrenal pubertal stages, post-stressor cortisol and DHEA were not coupled, but PI children who were at later pubertal stages demonstrated positive cortisol-DHEA coupling similar to that of the NA children. We suggest that these findings provide insights into processes which may underlie pubertal recalibration of the HPA axis.

Differential brain activity as a function of social evaluative stress in early adolescence: Brain function and salivary cortisol.

Understanding individual differences in neural responses to stressful environments is an important avenue of research throughout development. These differences may be especially critical during adolescence, which is characterized by opportunities for healthy development and increased susceptibility to the development of psychopathology. While the neural correlates of the psychosocial stress response have been investigated in adults, these links have not been explored during development. Using a new task, the Minnesota Imaging Stress Test in Children (MISTiC), differences in activation are found in fusiform gyrus, superior frontal gyrus, insula, and anterior cingulate cortex when comparing a stressful math task to a nonstressful math task. The MISTiC task successfully elicits cortisol responses in a similar proportion of adolescents as in behavioral studies while collecting brain imaging data. Cortisol responders and nonresponders did not differ in their perceived stress level or behavioral performance during the task despite differences in neuroendocrine function. Future research will be able to leverage the MISTiC task for many purposes, including probing associations between individual differences in stress responses with environmental conditions, personality differences, and the development of psychopathology.