Search

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans.

Entry into kindergarten is a developmental milestone that children may differentially experience as stressful, with implications for variability in neurobiological functioning. Guided by the goodness-of-fit framework, this study tested the hypothesis that kindergarten children's (N = 338) daily cortisol would be affected by the "match" or "mismatch" between children's temperament and qualities of the classroom relational context. The robustness of these associations was also explored among a separate sample of children in third grade (N = 165). Results among kindergarten children showed negative affectivity and overcontrolled temperament were positively related to cortisol expression within classrooms characterized by lower levels of teacher motivational support, but there was no relation between temperament and cortisol when motivational support was higher. Among third-grade children, negative affectivity was marginally positively related to cortisol at lower levels of teacher-child closeness and unrelated at higher levels of teacher-child closeness. Findings suggest children's cortisol expression depends on the extent to which specific temperamental characteristics "fit" within the relational and contextual qualities of the classroom environment, particularly as children navigate the new roles and relationships that emerge during the transition to formal schooling. Developmentally informed neurobiological research in classrooms may contribute to tailored programmatic efforts to support children's school adjustment.

Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for increased probability of reproducing before dying via a process of accelerated reproductive maturation. Using data from 73 females, we test the following propositions using path analysis: (a) greater exposure to prenatal stress predicts greater maternal depression and negative parenting in infancy, (b) which predicts elevated basal cortisol at 4.5 years, (c) which predicts accelerated adrenarcheal development, (d) which predicts more physical and mental health problems at age 18. Results prove generally consistent with these propositions, including a direct link from cortisol to mental health problems. DOoHaD investigators should consider including early sexual maturation as a core component linking early adversity and stress physiology with poor health later in life in females.

Despite widespread recognition that the physiological systems underlying stress reactivity are well coordinated at a neurobiological level, surprisingly little empirical attention has been given to delineating precisely how the systems actually interact with one another when confronted with stress. We examined cross-system response proclivities in anticipation of and following standardized laboratory challenges in 664 4- to 14-year-olds from four independent studies. In each study, measures of stress reactivity within both the locus coeruleus-norepinephrine system (i.e., the sympathetic and parasympathetic branches of the autonomic nervous system) and the corticotrophin releasing hormone system (i.e., the hypothalamic-pituitary-adrenal axis) were collected. Latent profile analyses revealed six distinctive patterns that recurred across the samples: moderate reactivity (average cross-system activation; 52%-80% of children across samples), parasympathetic-specific reactivity (2%-36%), anticipatory arousal (4%-9%), multisystem reactivity (7%-14%), hypothalamic-pituitary-adrenal axis specific reactivity (6%-7%), and underarousal (0%-2%). Groups meaningfully differed in socioeconomic status, family adversity, and age. Results highlight the sample-level reliability of children's neuroendocrine responses to stress and suggest important cross-system regularities that are linked to development and prior experiences and may have implications for subsequent physical and mental morbidity.

Study objectivesTo examine the patterns of insomnia and sleep-related movement from ages 4.5 to 9 years, their concurrent associations with mental health symptoms in childhood, and the longitudinal associations of sleep-problem persistence with mental health symptoms at ages 9 and 18 years.DesignA 14-year prospective follow-up study. Assessments included maternal report on the Children's Sleep Habits Questionnaire at ages 4.5 and 9, and child mental health symptoms via maternal report at age 4.5, multi-informant (child, teacher, mother) report at age 9, and adolescent report at age 18.SettingCommunity.ParticipantsA total of 396 children (51% female).InterventionsN/A.Measurements and resultsSleep problems were more common at age 4.5 than 9; symptoms of insomnia and abnormal sleep movement both had persistence rates of 9-10%. At age 4.5, insomnia was associated with hostile-aggressive and hyperactive-distractible behavior, but there were no significant associations for sleep movement. At age 9, both insomnia and sleep movement were associated with symptoms of depression, externalizing, and attention deficit hyperactivity disorder (ADHD). Insomnia persistence was associated with symptoms of depression, externalizing, and ADHD at age 9 and anxiety and externalizing at age 18; sleep- movement persistence was associated with externalizing and ADHD at age 9, and ADHD at age 18. The age 18 persistence effects for insomnia and anxiety and for sleep movement and ADHD were significant when controlling for earlier mental health.ConclusionsChildhood insomnia and sleep movement are common and associated with mental health symptoms. Their persistence from middle to late childhood predicts associations with specific types of mental health symptoms at age 18.

Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children's early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children's gender. To the authors' knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents' genomic DNA. (Contains 5 figures and 1 table.)

Our goals in this article were to use item response theory (IRT) to assess the relation of depressive symptoms to the underlying dimension of depression and to demonstrate how IRT-based measurement strategies can yield more reliable data about depression severity than conventional symptom counts. Participants were 3,403 children and adolescents from 12 contributing clinical and nonclinical samples; all participants had received the Kiddie Schedule of Affective Disorders and Schizophrenia for School-Aged Children. Results revealed that some symptoms reflected higher levels of depression and were more discriminating than others. Furthermore, use of IRT-based information about symptom severity and discriminability in the measurement of depression severity was shown to reduce measurement error and increase measurement fidelity. (Contains 5 footnotes, 6 tables, and 6 figures.)

The authors describe the development and initial validation of a home-based version of the Laboratory Temperament Assessment Battery (Lab-TAB), which was designed to assess childhood temperament with a comprehensive series of emotion-eliciting behavioral episodes. This article provides researchers with general guidelines for assessing specific behaviors using the Lab-TAB and for forming behavioral composites that correspond to commonly researched temperament dimensions. We used mother ratings and independent postvisit observer ratings to provide validity evidence in a community sample of 4.5-year-old children. 12 Lab-TAB behavioral episodes were employed, yielding 24 within-episode temperament components that collapsed into 9 higher level composites (Anger, Sadness, Fear, Shyness, Positive Expression, Approach, Active Engagement, Persistence, and Inhibitory Control). These dimensions of temperament are similar to those found in questionnaire-based assessments. Correlations among the 9 composites were low to moderate, suggesting relative independence. As expected, agreement between Lab-TAB measures and postvisit observer ratings was stronger than agreement between the Lab-TAB and mother questionnaire. However, for Active Engagement and Shyness, mother ratings did predict child behavior in the Lab-TAB quite well. Findings demonstrate the feasibility of emotion-eliciting temperament assessment methodologies, suggest appropriate methods for data aggregation into trait-level constructs and set some expectations for associations between Lab-TAB dimensions and the degree of cross-method convergence between the Lab-TAB and other commonly used temperament assessments. (Contains 1 figure, 9 tables and 1 footnote.)

Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental health as markers of genetic risk to test whether GxE predicted internalizing problems in a sample of 8-year-old twins. Multi-instrument composites were used to characterize both parent and child psychopathology, and five experiential risk factors (socioeconomic status, single parent upbringing, negative parent-child interactions, number of negative life events, negative impact of negative life events) composed a cumulative risk index. Results: We found consistent evidence for GxE for child internalizing problems, with significant interaction effects emerging both when genetic risk was indexed by co-twin mental health and when it was based on parent mental health. When co-twin mental health was used to estimate genetic risk, child internalizing problems were more heritable for children at low rather than high experiential risk. When parent mental health was used to estimate genetic risk, the association between genetic risk and internalizing problems was stronger for children at elevated experiential risk. Consideration of the interaction effect sizes helps to reconcile these findings. Conclusions: Our results suggest that the processes involved in both diathesis-stress and bioecological models of development may operate for child internalizing problems. Effect sizes indicated that the main effects of genetic and experiential risk were much better predictors of child internalizing problems than was their interaction.

Background: Many childhood psychiatric problems are transient. Consequently, screening procedures to accurately identify children with problems unlikely to remit and thus, in need of intervention, are of major public health concern. This study aimed to develop a universal school-based screening procedure based on the answers to three questions: (1) What are the broad patterns of mental health problems from kindergarten to grade 5? (2) What are the grade 5 outcomes of these patterns? (3) How early in school can children likely to develop the most impairing patterns be identified accurately? Methods: Mothers and teachers reported on a community sample (N = 328) of children's internalizing and externalizing symptoms in kindergarten and grades 1, 3, and 5. In grade 5, teachers reported on children's school-based functional impairments, physical health problems, and service use; mothers reported on children's specialty mental health care. Results: Four patterns distinguished children who (1) never evidenced symptoms; (2) evidenced only isolated symptoms; or evidenced recurrent symptoms, either (3) without or (4) with comorbid internalizing and externalizing. By grade 5, children with recurrent comorbid symptoms had the greatest impairments, physical health problems, and service use. These children can be identified quite accurately by grade 1. Conclusions: Universal screening at school entry can effectively identify children likely to develop recurrent comorbid symptoms, and would provide a basis for developing optimal targeted intervention programs.

We investigated whether differences in positive and negative emotional reactivity could be found in depressed preschoolers and preschoolers at risk for later internalizing symptoms relative to nondepressed/low risk comparison groups. Observational measures of emotional reactivity, used to derive a score of the balance between anger and sadness, were obtained and analyzed in independent samples. One study utilized cross-sectional data from preschoolers (M age = 4.6 years) with a current depressive syndrome and two nondepressed comparison groups. The other study utilized longitudinal data that assessed emotional reactivity at preschool age (M age = 4.5 years) and later mental health symptoms during the transition to primary school, allowing a retrospective determination of risk. Depressed and at-risk boys displayed more anger than sadness in contrast to girls in the same groups and in contrast to no disorder/low-risk controls. This finding was detected in depressed and "at risk for internalizing" boys who were not comorbid for externalizing problems. (Contains 2 tables and 2 figures.)

The psychometric properties and factor structure of the Dysfunctional Attitudes Scale were examined in a sample of 422 male and female adolescents (ages 12-17) with current major depressive disorder. The scale demonstrated high internal consistency ([alpha] = 0.93) and correlated significantly with self-report and interview-based measures of depression. Confirmatory factor analysis indicated that a correlated 2-factor model, with scales corresponding to perfectionism and need for social approval, provided a satisfactory fit to the data. The goodness-of-fit was equivalent across sexes and age groups. The findings support the use of the Dysfunctional Attitudes Scale and its subscales in the assessment of clinically depressed adolescents. (Contains 4 tables and 1 footnote.)

Objective: To study how early father involvement and children's biobehavioral sensitivity to social contexts interactively predict mental health symptoms in middle childhood. Method: Fathers' involvement in infant care and maternal symptoms of depression were prospectively ascertained in a community-based study of child health and development in Madison and Milwaukee, WI. In a subsample of 120 children, behavioral, autonomic, and adrenocortical reactivity to standardized challenges were measured as indicators of biobehavioral sensitivity to social context during a 4-hour home assessment in 1998, when the children were 7 years of age. Mental health symptoms were evaluated at age 9 years using parent, child, and teacher reports. Results: Early father involvement and children's biobehavioral sensitivity to context significantly and interactively predicted symptom severity. Among children experiencing low father involvement in infancy, behavioral, autonomic, and adrenocortical reactivity became risk factors for later mental health symptoms. The highest symptom severity scores were found for children with high autonomic reactivity that, as infants, had experienced low father involvement and mothers with symptoms of depression. Conclusions: Among children experiencing minimal paternal caretaking in infancy, heightened biobehavioral sensitivity to social contexts may be an important predisposing factor for the emergence of mental health symptoms in middle childhood. Such predispositions may be exacerbated by the presence of maternal depression. (Contains 3 figures and 2 tables.)

Examines time child is in child care, who gives it, the congruence of actual care and preferred care, and other factors that affect the marital satisfaction and emotional well-being of parents of infants. Found that father child care, when preferred, has positive effect on mother emotional well-being. (MT)

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1467-6494.2006.00422.x Byline: Nanmathi Manian (1), Alison A. Papadakis (2), Timothy J. Strauman (2), Marilyn J. Essex (3) Abstract: ABSTRACT Regulatory focus theory (RFT; Higgins, 1997) predicts that individual differences in the strength of promotion (ideal) and prevention (ought) orientations emerge from patterns of parent/child interactions that emphasize making good things happen versus keeping bad things from happening. This article examines the development of individual differences in the strength of children's promotion and prevention goals and presents selected findings from three studies exploring the origins of regulatory focus. We found a three-factor structure for parenting behaviors that differentiated between the presence/absence of positive outcomes versus the presence/absence of negative outcomes in two different data sets and validated that factor structure by examining its associations with maternal temperament. In turn, the parenting factors predicted individual differences in children's orientations to ideal and ought guides, and those associations were moderated by individual differences in child temperament. Author Affiliation: (1)National Institute of Child Health and Human Development (2)Duke University (3)University of Wisconsin-Madison Article note: Correspondence concerning this article may be sent to Nanmathi Manian, Child and Family Research, NICHD, Suite 8030, 6705 Rockledge Drive, Bethesda, MD 20892-7971. E-mail: maniann@mail.nih.gov.

This study investigates the influence of personality on adjustment to a particular life transition, community relocation. Participants were 285 women (average age = 69.5) who were interviewed once before they moved, and then multiple times after the move. Within the context of this multiwave design, personality traits were used to predict changes in depressive symptoms (DS) and self-esteem (SE) across the move. Neuroticism and Openness to Experience predicted increases in DS over time, whereas Extraversion and Openness predicted increases in SE. Stressful reactions to the move and sense of mastery about the move partially mediated these effects. The study documents the dynamic influence of personality on positive and negative aspects of adjustment and investigates differing routes through which such effects occur.