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.

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.

Female adolescents' early life stress and body mass index: Differential effects of anger and anxiety in response to rejection.

INTRODUCTION: Early life stress is linked to childhood obesity. As children enter adolescence, early life stress may be associated with increased rejection sensitivity, resulting in activation of behavioral and physiological changes that contribute to higher body mass index (BMI). Understanding the potential influence of rejection sensitivity on the association between early life stress and BMI is important to examine in female adolescents. For this secondary data analysis, we hypothesized that female adolescents with greater early life stress and greater rejection sensitivity would exhibit higher BMI-for-age 12 months later. METHODS: Seventy-eight adolescents (Mage = 13.1 years; 100% female sex; MBMI = 23.2 kg/m2 ) in the United States completed study procedures from 2012 to 2016. Among these procedures, the Psychosocial Schedule was used to assess cumulative early life stress and the Children's Rejection Sensitivity Questionnaire was used to assess anger and anxiety in response to rejection. Twelve months later, height and weight were measured to derive BMI-for-age. RESULTS: Higher early life stress was associated with higher BMI-for-age among female adolescents with low rejection-provoked anger (1 SD below the mean). However, this association was not observed among female adolescents with high rejection-provoked anger (1 SD above the mean). Finally, there was no significant interaction between early life stress and rejection-provoked anxiety in predicting BMI-for-age. CONCLUSIONS: Experiencing early life stress may interact with rejection-provoked anger, but not anxiety, to predict BMI-for-age. Findings inform a developmental perspective of how rejection sensitivity may influence the association between early life stress and early cardiometabolic risk.

The Interaction between Psychological Stress and Iron Status on Early-Life Neurodevelopmental Outcomes.

This review presents evidence from animal and human studies demonstrating the possible connection and significant impact of poor iron status and psychological distress on neurocognitive development during pregnancy and the neonatal period, with implications for long-term cognition. Stress and iron deficiency are independently prevalent and thus are frequently comorbid. While iron deficiency and early-life stress independently contribute to long-term neurodevelopmental alterations, their combined effects remain underexplored. Psychological stress responses may engage similar pathways as infectious stress, which alters fundamental iron metabolism processes and cause functional tissue-level iron deficiency. Psychological stress, analogous to but to a lesser degree than infectious stress, activates the hypothalamic-pituitary-adrenocortical (HPA) axis and increases proinflammatory cytokines. Chronic or severe stress is associated with dysregulated HPA axis functioning and a proinflammatory state. This dysregulation may disrupt iron absorption and utilization, likely mediated by the IL-6 activation of hepcidin, a molecule that impedes iron absorption and redistributes total body iron. This narrative review highlights suggestive studies investigating the relationship between psychological stress and iron status and outlines hypothesized mechanistic pathways connecting psychological stress exposure and iron metabolism. We examine findings regarding the overlapping impacts of early stress exposure to iron deficiency and children's neurocognitive development. We propose that studying the influence of psychological stress on iron metabolism is crucial for comprehending neurocognitive development in children exposed to prenatal and early postnatal stressors and for children at risk of early iron insufficiency. We recommend future directions for dual-exposure studies exploring iron as a potential mediating pathway between early stress and offspring neurodevelopment, offering opportunities for targeted interventions.

Placenta DNA methylation levels of the promoter region of the leptin receptor gene are associated with infant cortisol.

The intrauterine environment and early life stress regulation are widely recognized as an early foundation for lifelong physical and mental health. Methylation of CpG sites in the placenta represents an epigenetic modification that can potentially affect placental function, influence fetal development, and ultimately impact the health of offspring by programming the hypothalamic-pituitary-adrenal (HPA) axis stress response during prenatal development. Leptin, an adipokine produced by the placenta, is essential for energy homeostasis. It is also epigenetically regulated by promoter DNA methylation. Mounting evidence suggests that leptin also affects the stress response system. Though heterogeneity in the early stress response system may influence life-long mental and physical health, few studies explicitly examine the heterogeneity in the newborn stress response system. Less is known about leptin's association with the human hypothalamic-pituitary-adrenocortical (HPA) axis early in life. This study sought to serve as a proof of concept study investigating the relationship between newborn cortisol output trajectories and placental leptin DNA methylation in 117 healthy newborns from socioeconomically and racially- and ethnically-diverse families. We characterized heterogeneity in newborn cortisol output during the NICU Network Neurobehavioral Scales exam in the first week of life with latent growth mixture models. We then evaluated whether leptin promoter (LEP) methylation in placental samples was associated with newborn cortisol trajectories. Our findings suggest that increased placental LEP methylation, which corresponds to decreased leptin production, is associated with infant cortisol trajectories marked by increased cortisol output in the NNNS exam. These results provide important insights into the role of placental leptin DNA methylation in human newborn HPA axis development and subsequent developmental origins of health and disease processes.

Maternal prenatal cortisol and the interaction of income and pre-pregnancy body mass index are independently associated with newborn cortisol.

While extensive research has supported the developmental programming hypothesis regarding contributions of prenatal psychosocial or nutritional adversity to offspring stress physiology, fewer studies consider both exposures together with maternal stress physiology. This study examined newborn cortisol output during a stressor as a function of maternal pre-pregnancy health status and nutritional history (pre-pregnancy body mass index [PPBMI]), economic resources (household income), and maternal cortisol awakening response (mCAR) in late pregnancy. Participants were 102 mother-infant pairs from an economically and racial/ethnically diverse sample. Offspring salivary cortisol response to a neurobehavioral exam was assessed at 1 month. Income and maternal PPBMI were positively associated with mCAR in late pregnancy. mCAR was positively related to 1-month newborn cortisol response. The interaction of income and PPBMI was positively associated with newborn cortisol output during an exam at 1-month. Mothers with the highest PPBMI and lowest income had offspring with higher cortisol responses than offspring of mothers with higher income and lower PPBMI. There was no evidence of indirect mediation effects of predictors (PPBMI, income, and interaction) on infant cortisol via mCAR. The differential effects of the interaction of PPBMI and income suggest that these exposures influence infant cortisol output in the context of one another, independent of maternal pregnancy cortisol.

Early-life adversity is associated with poor iron status in infancy.

Exposure to early-life adversity (ELA) and iron deficiency early in life are known risk factors for suboptimal brain and socioemotional development. Iron deficiency may arise from and co-occur with ELA, which could negatively affect development. In the present study, we investigated whether ELA is associated with iron deficiency in infants receiving no iron supplementation. This study is a secondary analysis of extant data collected in the 1990s; participants were healthy infants from working-class communities in Santiago, Chile (N = 534, 45.5% female). We measured stressful life events, maternal depression, and low home support for child development during infancy and assessed iron status when the infant was 12 months old. Slightly more than half of the infants were iron-deficient (51%), and 25.8% were iron-deficient anemic at 12 months. Results indicated that ELA was associated with lower iron levels and iron deficiency at 12 months. The findings are consistent with animal and human prenatal models of stress and iron status and provide evidence of the association between postnatal ELA and iron status in humans. The findings also highlight a nutritional pathway by which ELA may impact development and present a nutritionally-focused avenue for future research on ELA and psychopathology.

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.

Refugee Children and Interventions for Depression: A Review of Current Interventions and Implications of the Ecological Context.

As of 2018, over 25.4 million people worldwide meet the criteria to be considered refugees, the highest number on record. Over half of these individuals are under 18 years old, leaving approximately 12 million children to cope with the trauma and stress typically encountered by refugees. Increased rates of depression in this population are well-documented in the literature. This article reviews the ecological determinants of depression for displaced children and current empirical methods for alleviating depression across contexts. PubMed and PsycINFO databases were reviewed for articles that met the following criteria for inclusion: published between January 1, 2000, and April 16, 2020; peer-reviewed empirical article; in English; reviewed an intervention targeting depression; and included a sample of refugees 18 years of age or younger. Sixteen interventions met inclusion criteria and were assessed using an ecological framework. The programs were analyzed for several methodological and outcome factors including intervention type, retention rate, participant demographics, participant country of origin and host country, ecological framework, and effectiveness. Major findings suggest that interventions including caregivers, involving the child's community, addressing multiple contexts, and that are culturally informed may improve outcomes. This article presents research surrounding risk and protective factors for depression within each context to inform existing interventions and presents additional avenues for services to meet the needs of refugee youth across contexts.

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 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.

Integrating anthropometric and cardiometabolic health methods in stress, early experiences, and development (SEED) science.

Within Stress, Early Experiences, and Development (SEED) science, there is a growing body of research demonstrating complex associations not only between stress, development, and psychopathology, but also with chronic disease risk factors. We argue that it is important for SEED researchers to consider including child anthropometric and physical health measures to more comprehensively capture processes of risk and resilience. Broader adoption of harmonized anthropometry and health measures in SEED research will facilitate collaborations, yielding larger datasets for research in high-risk populations, and greater opportunity to replicate existing findings. In this review, we identify optimal anthropometric and cardiometabolic health measurement methods used from infancy through adolescence, including those that are low-burden and inexpensive. Methods covered include: waist, hip, and head circumference, height, length, weight, pubertal development, body composition, blood pressure, arterial stiffness, carotid intima media thickness, and serum measures of cardiometabolic risk and inflammation. We provide resources for SEED researchers to integrate these methods into projects or to better understand these methods when reading the literature as well as where to find collaborators for more in-depth studies incorporating these measures. With broader integration of psychological and physical health measures in SEED research, we can better inform theory and interventions to promote health and resilience in individuals who have experienced early stress.

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.

Validation of an online version of the Trier Social Stress Test in a study of adolescents.

INTRODUCTION: The Trier Social Stress Test (TSST) is the most widely used protocol for activating a stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis and other stress-mediating systems. A number of variants of the TSST exist, including ones for children, groups, and virtual reality. All of these versions, though, require in-person assessment. The COVID-19 pandemic has made in-person assessment impossible or extremely difficult and potentially dangerous. The purpose of this study was to validate a completely remote, online, version of the TSST for children. METHOD: A sample of 68 (27 female) 15- and 16-year old participants were administered the TSST-Online (TSST-OL) during the late afternoon hours (3-6 p.m. start time). The participants, judges (one male, one female), and experimenter (female) all joined the assessment from their own homes via the online platform, ZOOM™. Two sessions were conducted, one to obtain consent, explain procedures, work with the family to arrange the computer and room set-up for the TSST-OL and one within two weeks to conduct the procedure. The participants were trained to take their own saliva samples and a saliva sampling kit was mailed to the home in between the first and second session. The samples were then mailed to the researchers within a day of collection. The participant was observed during saliva collection to determine correct procedures were followed. Salivary cortisol, salivary α-amylase and self-reports of stress were measured multiple times over the second session. RESULTS: rmANOVAs yielded a significant effect of trials, for cortisol, F(1.37,90.46) = 15.13, p = .001, sAA, F(2.75,146.68) = 6.91, p = .001, and self-rated stress, F(3.43,222.69) = 118.73, p = .001. There were no significant sex by trials interactions for any measure, although females reported more stress than males, F(1,65) = 9.14, p = .004. For cortisol, from baseline to expected peak (30 min after the onset of speech preparation), the Cohen's effect size was dz = 0.57. Using 1.5 nmol/l (or 0.54 µg/dl) as the criterion for a response (Miller, Plessow, Kirschaum, & Stalder, 2013), 63% of the participants produced a significant increase in cortisol. CONCLUSIONS: The responses to the TSST-OL are consistent with in-person responses among children and adolescents (see recent meta-analysis (Seddon et al., 2020). The protocol is a viable way of assessing reactivity of the HPA axis and other stress systems without needing to bring the participant into the research laboratory. This method will be useful during periods of widespread infection. It should also work to study populations who all live too far from the research laboratory to be assessed in person.

Selective inflammatory propensities in adopted adolescents institutionalized as infants.

This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3-21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1ß (IL-1ß) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.

Pathways to inflammation in adolescence through early adversity, childhood depressive symptoms, and body mass index: A prospective longitudinal study of Chilean infants.

Early adversity, depression, and obesity are associated with increases in low-grade inflammation. However, there are few prospective and longitudinal studies to elucidate how these associations unfold in children. The present study used latent growth curve models to examine pathways between family adversity in infancy, depressive symptoms in childhood, body mass index (BMI) in childhood, and inflammation in adolescence (age = 16-18). The study is an adolescent follow-up of infants from working-class communities around Santiago, Chile, who participated in a preventive trial of iron supplementation at 6 months of age. Anthropometrics, stressful life events, maternal depression, socioeconomic status, and developmental assessments were measured at 12 months, 5 years, 10 years, and adolescence. In adolescence, participants provided blood samples for high-sensitivity C-reactive protein (hsCRP) assessment. Greater exposure to early adversity in the form of interpersonal conflict stress in infancy indirectly associated with increased hsCRP through its association to increased intercept and slope of childhood BMI. Depressive symptoms at any time were not directly or indirectly associated with increased hsCRP. These findings contribute to our understanding of how early family adversity and its associations with obesity and depressive symptoms across childhood are linked to low-grade, chronic inflammation in adolescence. The model identified as best capturing the data supported the pivotal role of childhood BMI in explaining how early-life adversity is associated with inflammation in adolescence.

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.

Infant Psychosocial Environment Predicts Adolescent Cardiometabolic Risk: A Prospective Study.

OBJECTIVE: To prospectively assess whether the infant psychosocial environment was associated with cardiometabolic risk as early as adolescence. STUDY DESIGN: Participants were recruited in Santiago, Chile, and have been followed from infancy. Inclusion criteria included healthy infants with birth weight ≥3 kg and a stable caregiver. The psychosocial environment, including depressive symptoms, stressful life events, poor support for child development, father absence, and socioeconomic status, was reported by mothers at 6-12 months. Body mass index (BMI) z score was assessed at 5 and 10 years. BMI z score, waist-to-hip ratio, systolic and diastolic blood pressure, fat mass and body fat percentage, fasting glucose, total and high-density lipoprotein cholesterol, and homeostatic model of insulin resistance were tested in adolescence. RESULTS: Adolescents ranged from 16 to 18 years of age (n = 588; 48.1% female). A poorer infant psychosocial environment was associated with BMI z score at 10 years (ß = 0.10, 95% CI = 0.00-0.19) and in adolescence (ß = 0.15, 95% CI = 0.06-0.24) but not at 5 years. A poorer infant psychosocial environment was associated with higher blood pressure (ß = 0.15, 95% CI = 0.05-0.24), greater anthropometric risk (ß = 0.13, 95% CI = 0.03-0.22), greater biomarker (triglycerides, homeostatic model assessment of insulin resistance, total cholesterol) risk (ß = 0.12, 95% CI = 0.02-0.22), and a higher likelihood of metabolic syndrome in adolescence (aOR = 1.50; 95% CI = 1.06-2.12). CONCLUSIONS: These findings demonstrate that a poorer infant psychosocial environment was associated with greater adolescent cardiometabolic risk. The results support screening for infants' psychosocial environments and further research into causality, mechanisms, prevention, and intervention.

Persistent skewing of the T-cell profile in adolescents adopted internationally from institutional care.

The developing immune system is an adaptive system, primed by antigens, responsive to infectious pathogens, and can be affected by other aspects of the early rearing environment, including deviations from the normal provision of parental care. We investigated whether early rearing in an institutional setting, even when followed by years living in supportive and well-resourced families, would be associated with a persistent shift in T cell profiles. Immunophenotyping was used to enumerate CD4+ CD57+ and CD8+ CD57+ subsets, with gating strategies employed to differentiate naïve, central-memory, effector-memory, and terminally differentiated EM cells expressing CD45RA (TEMRA). Blood samples were collected from 96 adolescents, and PBMC isolated via Ficol gradient, followed by an optimized immunophenotypic characterization. CMV antibody titers were determined via ELISA. Adopted adolescents had lower CD4/CD8 ratios than did the control adolescents. Early rearing had a significant effect on the T cells, especially the CD8+ CD57+ CM, EM, and TEMRA cells and the CD4+ CD57+ EM cells. Adolescents who had spent their infancy in institutions before adoption were more likely to be seropositive for CMV, with higher antibody titers. CMV antibody titers were significantly correlated with the percentages of all CD8+ CD57+ cell subsets. In the statistical modeling, CMV antibody titer also completely mediated the relationship between institutional exposure and the ratio of CD4-to-CD8 cells, as well as the percentages of CD4+ CD57+ and CD8+ CD57+ subsets. These findings demonstrate that persistent immune differences are still evident even years after adoption by supportive American families. The shift in the T cells was associated with being a latent carrier of CMV and may reflect the role of specific T cell subsets in Herpes virus containment. In older adults, sustained CMV antigen persistence and immunoregulatory containment ultimately contributes to an accumulation of differentiated T cells with a decreased proliferative capacity and to immune senescence.

Early Life Adversity with Height Stunting Is Associated with Cardiometabolic Risk in Adolescents Independent of Body Mass Index.

OBJECTIVE: To evaluate cardiovascular and metabolic function in youths adopted internationally from orphanages/institutions (postinstitutionalized) who were height-stunted at adoption. STUDY DESIGN: A total of 30 postinstitutionalized youths (age, 9-18 years; body mass index [BMI] percentile, 7.2-90.4) who were height-stunted at adoption were compared with age- and BMI percentile-matched youths (n = 90). Measurements included total body fat and visceral adipose tissue (dual radiograph absorptiometry), arterial stiffness (augmentation index and pulse wave velocity), cardiac autonomic function (heart rate variability), blood pressure, and fasting lipid, glucose, and insulin levels. Linear regression analyses were computed controlling for parent education, age, trunk tissue fat, height-for-age, sex, and race. RESULTS: Compared with controls of the same age, sex, and BMI, the postinstitutionalized children had higher systolic blood pressure (P = .018), augmentation index (P= .033), total cholesterol (P= .047), low-density lipoprotein cholesterol (P= .03), triglycerides (P= .048), insulin (P= .005), and HOMA-IR (P= .01) values. The postinstitutionalized children had a lower low-frequency to high-frequency ratio (P = .008), indicating lower sympathetic tone, as well as a lower total lean mass (P = .016), a lower gynoid lean mass (P = .039), and a higher proportion of trunk tissue fat (P = .017). The postinstitutionalized and control children did not differ in any other body composition measures. CONCLUSIONS: Early life stress, as represented by height-stunted growth in institutional care, may be associated with early pathways to cardiovascular and metabolic risk in youths even after moving into well-resourced homes early in life and in the absence of increased adiposity. These findings suggest that postinstitutionalized youths with a history of height stunting may need to be closely monitored for emergent cardiometabolic risk factors.