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.

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.

Lingering Effects of Early Institutional Rearing and Cytomegalovirus Infection on the Natural Killer Cell Repertoire of Adopted Adolescents.

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56bright NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56dim lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.

Cumulative environmental stress and emerging cardiometabolic risk during childhood.

OBJECTIVE: To prospectively evaluate the relationship between cumulative environmental stress and cardiometabolic risk in middle childhood, and to examine whether hair cortisol, a measure of hypothalamic pituitary adrenal-axis activity, mediates this relationship. METHODS: In a cohort of children from low-income households (n = 320; 59% Hispanic, 23% Black, body mass index (BMI) percentile >50th at enrollment), environmental stressors including family and neighbourhood factors representing disadvantage/deprivation, and cortisol concentrations from hair samples, were measured over five timepoints beginning when children were 2-4 years old. Cardiometabolic risk factors (i.e., BMI, blood pressure, lipids, blood sugar, C-reactive protein) were measured at the final timepoint when children were 7-11 years of age. RESULTS: In adjusted logistic regression models, greater cumulative environmental stress was associated with a higher likelihood of elevated cardiometabolic risk in middle childhood (p = 0.01). Children from minoritized racial/ethnic groups had a higher prevalence of both stressors and cardiometabolic risk factors. Cumulative environmental stress was associated with higher hair cortisol concentrations (p < 0.01). However, hair cortisol was not directly associated with cardiometabolic risk factors and did not explain the association between environmental stress and cardiometabolic risk in causal mediation analysis. CONCLUSIONS: The influence of cumulative stress on cardiometabolic health can be observed in middle childhood and may contribute to cardiometabolic health disparities, highlighting the importance of public health interventions to mitigate disadvantage.

Early Life Stress Is Associated with Alterations in Lymphocyte Subsets Independent of Increased Inflammation in Adolescents.

Early life stress (ELS) is linked to an elevated risk of poor health and early mortality, with emerging evidence pointing to the pivotal role of the immune system in long-term health outcomes. While recent research has focused on the impact of ELS on inflammation, this study examined the impact of ELS on immune function, including CMV seropositivity, inflammatory cytokines, and lymphocyte cell subsets in an adolescent cohort. This study used data from the Early Life Stress and Cardiometabolic Health in Adolescence Study (N = 191, aged 12 to 21 years, N = 95 exposed to ELS). We employed multiple regression to investigate the association between ELS, characterized by early institutional care, cytomegalovirus (CMV) seropositivity (determined by chemiluminescent immunoassay), inflammation (CRP, IL-6, and TNF-a determined by ELISA), and twenty-one immune cell subsets characterized by flow cytometry (sixteen T cell subsets and five B cell subsets). Results reveal a significant association between ELS and lymphocytes that was independent of the association between ELS and inflammation: ELS was associated with increased effector memory helper T cells, effector memory cytotoxic T cells, senescent T cells, senescent B cells, and IgD- memory B cells compared to non-adopted youth. ELS was also associated with reduced percentages of helper T cells and naive cytotoxic T cells. Exploratory analyses found that the association between ELS and fewer helper T cells and increased cytotoxic T cells remained even in cytomegalovirus (CMV) seronegative youth. These findings suggest that ELS is associated with cell subsets that are linked to early mortality risk in older populations and markers of replicative senescence, separate from inflammation, in adolescents.

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.

The Development of Stress Reactivity and Regulation in Children and Adolescents.

Adversity experienced in early life can have detrimental effects on physical and mental health. One pathway in which these effects occur is through the hypothalamic-pituitary-adrenal (HPA) axis, a key physiological stress-mediating system. In this review, we discuss the theoretical perspectives that guide stress reactivity and regulation research, the anatomy and physiology of the axis, developmental changes in the axis and its regulation, brain systems regulating stress, the role of genetic and epigenetics variation in axis development, sensitive periods in stress system calibration, the social regulation of stress (i.e., social buffering), and emerging research areas in the study of stress physiology and development. Understanding the development of stress reactivity and regulation is crucial for uncovering how early adverse experiences influence mental and physical health.

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.

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.

Mental-Health Trajectories of U.S. Parents With Young Children During the COVID-19 Pandemic: A Universal Introduction of Risk.

Parents of young children were a subgroup of the population identified early in the pandemic as experiencing significant mental-health symptoms. Using a longitudinal sample of 3,085 parents from across the United States who had a child or children age 0 to 5, in the present study, we identified parental mental-health trajectories from April to November 2020 predicted by pre-COVID-19 cumulative risk and COVID-19-specific risk factors. Both growth-mixture modeling and latent-growth-curve modeling were used to test the relationship between risk factors and parent mental health. Pre-COVID-19 cumulative risk and COVID-19-specific risks of financial strain, decreased employment, and increased family conflict were salient risk factors predicting poor mental-health trajectories across both modeling approaches. These finding have public-health implications because prolonged exposure to mental-health symptoms in parents constitutes a risk factor for child development.

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.

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.

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.

Race/ethnicity and age associations with hair cortisol concentrations among children studied longitudinally from early through middle childhood.

A total of 513 children were included in this secondary analysis of data from the NET-Works trial of low income children at risk for obesity. The purpose of the analysis was to examine HCC longitudinally over 5 assessments from early through middle childhood with the goal of i) determining if there were racial/ethnic differences in HCC, and if so, how early in childhood these differences could be observed; and (ii) whether racial/ethnic differences in HCC reflected structural and family-level indicators of disadvantage. The sample consisted of children from diverse racial/ethnic backgrounds: Black, including Hispanic Black (N = 156), non-Hispanic White (N = 67) and Non-Black Hispanic (N = 290) children. As the largest group, the last group was used as the reference group in analyses. Structural and family-level indicators of disadvantage, including the neighborhood child opportunity index (COI), family income, and parent perceived neighborhood safety, were collected at each assessment. The results showed higher HCC among Black children beginning as early as 2-4 years of age than non-Black Hispanic children who did not differ from non-Hispanic White children. Although family income and COI were lower for children from minoritized racial-ethnic backgrounds, entering these measures as covariates did not reduce the difference in HCC between Black children and the other two groups. The results also showed that HCC initially decreased with age and then plateaued, with no evidence that this pattern differed by race/ethnicity. Because of the potential health risks of chronically elevated cortisol concentrations, these data argue for increased attention to the myriad of factors (oppressive structures, systems, and interpersonal experiences) that likely contribute to elevated cortisol levels among Black children.

Material hardship level and unpredictability in relation to U.S. households' family interactions and emotional well-being: Insights from the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has been recognized to provide rare insight to advance the scientific understanding of early life adversity, such as material hardship. During the COVID-19 pandemic, material hardship (i.e., difficulty paying for basic needs) in families of young children has had detrimental effects on caregivers' and children's well-being. In addition to the degree of material hardship, the week-to-week and month-to-month unpredictability of hardship status may add to families' stress and worsen well-being. This study examined the magnitude of and mechanisms underlying the effects of material hardship level and unpredictability on the well-being of U.S. households with young children during the pandemic. METHODS: Data were drawn from the RAPID project, a large ongoing national study that used weekly/biweekly online surveys to investigate the pandemic impact on U.S. households with young children. The current study leveraged data from 4621 families who provided at least three responses between April 2020 and October 2021. RESULTS: Findings indicated that racial/ethnic minorities and lower-income households experienced higher levels of material hardship and unpredictability during the pandemic, compared to their White or higher-income counterparts. Levels of pandemic-related material hardship and hardship unpredictability were both significantly associated with worsened well-being among caregivers and children. Finally, the effects of hardship level and unpredictability on well-being outcomes were partially mediated through disrupted family routines. CONCLUSIONS: The findings from this study highlight that ensuring equal and adequate access to financial resources, as well as promoting financial stability for households with young children are both critical for maintaining functional family dynamics and promoting caregivers' and children's optimal well-being.

Household food insecurity and obesity risk in preschool-aged children: A three-year prospective study.

BACKGROUND: Household food insecurity (FI) is a pressing social, economic and public health issue. However, little is known regarding the effect of FI exposure during the first few years of life, the most active postnatal time for neurobiological and physiological development, on patterns of weight gain during early childhood. It is also unknown whether dietary quality would serve as a pathway through which FI affects children's weight development. METHOD: This was a secondary data analysis from a three-year randomized clinical trial with five hundred and thirty-four parent/child dyads. Household FI in the past year was reported by parents at baseline when children were 2-4 years of age using the USDA Household Food Security Survey Module-Six Item Short Form. Children's dietary quality at baseline was measured by the US Department of Agriculture Healthy Eating Index (HEI). Child body mass index (BMI) was measured following standardized protocols at baseline and 12-, 24-, and 36-month follow-up. A latent growth curve model was used to examine 1) the association between baseline FI and sex-and-age-adjusted BMI z-scores in children and 2) the HEI pathway between the FI- BMI association. RESULTS: FI early in life was associated with higher baseline BMI z-scores. Children who had higher BMI at baseline maintained their higher BMI status over the next three years. Children's dietary intake quality did not explain the association between baseline FI and BMI z-scores. CONCLUSION: Early exposure to FI was associated with higher BMI in children as early as two years of age, setting them up for an increased likelihood of persistently high BMI-for-age in later childhood. These data suggest that the first few years may be a critical time for developing obesity risk, calling for policy and practices designed for early intervention of food insecurity.

Calibration and recalibration of stress response systems across development: Implications for mental and physical health.

Decades of human and animal research demonstrates that stress responsive neuroendocrine systems calibrate to the harshness of environmental conditions during fetal and early postnatal life. Emerging evidence indicates that if conditions change markedly over childhood, the hypothalamic pituitary adrenal (HPA) axis may recalibrate during puberty, another period that involves heightened neural plasticity and rapid maturation of neurobehavioral systems. These recent findings have prompted increased interest in the potential for stress system calibration/recalibration over development. To direct research in this area, this chapter integrates and discusses theoretical perspectives and empirical evidence pertaining to calibration and recalibration of the stress response. We describe how these concepts relate to other constructs, including sensitive periods, plasticity, and programming. We then consider four potential periods of calibration/recalibration: fetal, infancy, puberty, and pregnancy/lactation. In each section, we discuss evidence that the HPA and/or sympathetic medullary adrenal (SAM) system undergoes developmental change, rendering it more plastic and amenable to shift its activity in response to environmental conditions. We also review findings that the impacts of environmental harshness on stress responding persist beyond these periods. We then articulate that marked change in the quality of the environment (from harsh to benign or vice versa) is required in order for recalibration to occur, and that recalibration would result in shifts in stress responding to more closely align with the profiles of individuals who have experienced these conditions throughout life. Finally, we reflect on whether recalibration of the HPA and SAM system may extend to the other stress-responsive neurobehavioral systems.

Translating the Biology of Adversity and Resilience Into New Measures for Pediatric Practice.

As the science of adversity and resilience advances, and public awareness of the health consequences of stress grows, primary care providers are being increasingly asked to address the effects of adverse experiences on child wellbeing. Given limited tools for assessing these effects early in life, the authors explore how enhanced capacity to measure stress activation directly in young children could transform the role and scope of pediatric practice. When employed within a trusted relationship between caregivers and clinicians, selective use of biological measures of stress responses would help address the documented limitations of rating scales of adverse childhood experiences as a primary indicator of individual risk and strengthen the ability to focus on variation in intervention needs, assess their effectiveness, and guide ongoing management. The authors provide an overview of the potential benefits and risks of such expanded measurement capacity, as well as an introduction to candidate indicators that might be employed in an office setting. The ultimate value of such measures for both pediatricians and parents will require vigilant attention to the ethical responsibilities of assuring their correct interpretation and minimizing the harm of inappropriate labeling, especially for children and families experiencing the hardships and threats of racism, poverty, and other structural inequities. Whereas much work remains to be done to advance measurement development and ensure its equitable use, the potential of validated markers of stress activation and resilience to strengthen the impact of primary health care on the lives of young children facing significant adversity demands increased attention.

Using machine learning to understand age and gender classification based on infant temperament.

Age and gender differences are prominent in the temperament literature, with the former particularly salient in infancy and the latter noted as early as the first year of life. This study represents a meta-analysis utilizing Infant Behavior Questionnaire-Revised (IBQ-R) data collected across multiple laboratories (N = 4438) to overcome limitations of smaller samples in elucidating links among temperament, age, and gender in early childhood. Algorithmic modeling techniques were leveraged to discern the extent to which the 14 IBQ-R subscale scores accurately classified participating children as boys (n = 2,298) and girls (n = 2,093), and into three age groups: youngest (< 24 weeks; n = 1,102), mid-range (24 to 48 weeks; n = 2,557), and oldest (> 48 weeks; n = 779). Additionally, simultaneous classification into age and gender categories was performed, providing an opportunity to consider the extent to which gender differences in temperament are informed by infant age. Results indicated that overall age group classification was more accurate than child gender models, suggesting that age-related changes are more salient than gender differences in early childhood with respect to temperament attributes. However, gender-based classification was superior in the oldest age group, suggesting temperament differences between boys and girls are accentuated with development. Fear emerged as the subscale contributing to accurate classifications most notably overall. This study leads infancy research and meta-analytic investigations more broadly in a new direction as a methodological demonstration, and also provides most optimal comparative data for the IBQ-R based on the largest and most representative dataset to date.