Darlene A. Kertes

Early deprivation and home basal cortisol levels: A study of internationally adopted children

Animal studies reveal that early deprivation impairs regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, potentially increasing vulnerability to stressors throughout life. To examine early deprivation effects on basal HPA axis activity in humans, basal cortisol levels were examined in 164 internationally adopted children who had experienced varying degrees of preadoption deprivation. Duration of institutional care, age at adoption, and parent ratings of preadoption neglect indexed a latent factor of Deprived Care. Adoption measures of height and weight standardized to World Health Organisation norms indexed a latent factor of Growth Delay that was viewed as another reflection of deprivation. Cortisol samples were collected 3.3-11.6 years postadoption (Md = 7.3 years) at home on 3 days approximately 30 min after wakeup and before bedtime. Both early a.m. levels and the decrease in cortisol across the day were examined. A structural equation model revealed that preadoption Deprived Care predicted Growth Delay at adoption and Growth Delay predicted higher morning cortisol levels and a larger diurnal cortisol decrease.

Inhibited temperament and parent emotional availability differentially predict young children's cortisol responses to novel social and nonsocial events

Preschool-aged children (n = 274) were examined in the laboratory to assess behavioral and cortisol responses to nonsocial and social threat. Parents also responded to scales on the Childrens Behavior Questionnaire reflecting exuberant approach to novel/risky activities (reversed scored) and shyness. Multi-method measures of Nonsocial and Social Inhibition were computed. Parents and children were observed engaging in a series of interactive tasks and the Emotional Availability scales were scored for parental sensitivity, nonintrusiveness, nonhostility, and structuring. These scores were factored to yield one measure of Parenting Quality. Analyses revealed that Nonsocial and Social Inhibition could be distinguished and that associations with cortisol response were stressor specific. Moderation analyses revealed that parenting quality buffered cortisol elevations for extremely socially, but not nonsocially inhibited children. These findings are consistent with evidence that sensitive, supportive parenting is an important buffer of the HPA axis response to threat in infants and toddlers, and extends this finding to the preschool period.

Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo.

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict-ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes.

Identifying atypical cortisol patterns in young children: The benefits of group-based trajectory modeling

The introduction of growth curve modeling into the field of neuroendocrinology has enabled researchers to examine mean patterns of change in unbalanced and/or incomplete repeated measures data. However, growth curve modeling assumes population homogeneity, or that all individuals follow roughly the same pattern of change, with differences expressed as deviation around the mean curve. Group-based trajectory modeling, in contrast, is designed for heterogeneous populations and as a result is able to identify atypical patterns of change over time that may exist within a population. To illustrate the strengths and weaknesses of each technique, we apply both to a sample of diurnal cortisol data measured at home in young children (N=106, 46 male, M age=3.81 years, S.D.=0.24). We find three distinct trajectories of cortisol and demonstrate that the members of these trajectories are measurably different in terms of cortisol levels across context and time and in terms of the relationship between behavioral problems and parenting. At the same time, our growth curve analysis finds differential response patterns for high vs. low internalizing children with high vs. low parenting quality. We discuss these results in terms of their implications for the proper application of each method.

Latent state trait modeling of children's cortisol at two points of the diurnal cycle.

One challenge in examining stable individual differences in basal activity of the HPA axis is controlling for internally or externally based situational factors that lead to day-to-day variation in ambulatory cortisol. Disturbed basal activity is of particular interest in studies with children, for whom a dysregulated HPA axis may play an etiologic role in emotional or health outcomes. The purpose of this study was to determine whether trait vs. situationally specific sources of variation can be identified at different points of the diurnal cycle in children and if so, whether state and trait components vary according to time of measurement. Early morning and late evening salivary cortisol was collected from 164 children aged 7 to 11 years. Samples were collected 30 min after wake-up and 30 min before bedtime on 3 weekdays. State, trait, and error components of cortisol levels were assessed using a latent state trait model. Possible influences of sampling day and outlier treatment on parameter estimates were examined. The results showed that a latent trait factor superimposed on state residuals and measurement error was identified for both early morning and late evening cortisol. Model fit was excellent and criteria for invariance tests were met. Trait factors accounted for 41% and 57% of the variance in morning and evening cortisol, respectively. These findings suggest cortisol attributed to trait factors can be identified and are of substantial magnitude at both the peak and nadir of the diurnal cycle. Latent state trait modeling is a potentially useful tool in understanding the role of stable individual differences in cortisol levels for development and health.

Cortisol and DHEA in Development and Psychopathology.

&NA; Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short‐ and long‐term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co‐actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age‐related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research. HighlightsDHEA and cortisol are co‐synthesized and released from the adrenals.Research suggests quantifying a ratio of the hormones may be a useful biomarker.Physiologic data support the notion of opposing effects of DHEA and cortisol.Dramatic shifts in DHEA production are observed during development.Absolute and relative hormone levels are linked with developmental psychopathology.

Pathway based analysis of genotypes in relation to alcohol dependence

We introduce a method for detecting variants in several genes of related function with small effect on a phenotype of interest. Our method uses logistic regression to test whether multiple alleles within a functional set have significantly higher than expected predictive value, even though none individually may have strong individual effects. We illustrate this method by testing seven gene sets (including 48 genes), from a study with1350 single nucleotide polymorphisms in 130 addiction candidate genes studied in a sample of 575 alcohol dependence (AD) cases and 530 controls. We conclude that AD is related to variation in genes participating in Glutamate and γ-amino butyric acid signaling, as has been reported elsewhere, and in stress response pathways, but not with genes in several other systems implicated in other drugs of abuse.

A Role for the Placenta in Programming Maternal Mood and Childhood Behavioural Disorders

Substantial data demonstrate that the early‐life environment, including in utero, plays a key role in later life disease. In particular, maternal stress during pregnancy has been linked to adverse behavioural and emotional outcomes in children. Data from human cohort studies and experimental animal models suggest that modulation of the developing epigenome in the foetus by maternal stress may contribute to the foetal programming of disease. Here, we summarise insights gained from recent studies that may advance our understanding of the role of the placenta in mediating the association between maternal mood disorders and offspring outcomes. First, the placenta provides a record of exposures during pregnancy, as indicated by changes in the placental trancriptome and epigenome. Second, prenatal maternal mood may alter placental function to adversely impact foetal and child development. Finally, we discuss the less well established but interesting possibility that altered placental function, more specifically changes in placental hormones, may adversely affect maternal mood and later maternal behaviour, which can also have consequence for offspring well‐being.

Effect of OPRM1 and stressful life events on symptoms of major depression in African American adolescents.

BACKGROUND In a community sample of low-income African American adolescents, we tested the interactive effects of variation in the mu 1 opioid receptor (OPRM1) gene and the occurrence of stressful life events on symptoms of depression. METHOD Interactive effects of 24 OPRM1 simple nucleotide polymorphisms (SNP) and adolescent report of stressful life events on depression were tested using multilevel regressions. SNPs were dummy coded to test both additive and dominate forms of coding. RESULTS Five OPRM1 SNPs showed significant evidence of interaction with stressful life events to alter depression risk (or symptoms) after adjusting for multiple testing and the correlated nature of the SNPs. Follow-up analyses showed significant differences based on OPRM1 genotype at both lower and higher frequencies of stressful life events, suggesting that participants with a copy of the minor allele on OPRM1 SNPs rs524731, rs9478503, rs3778157, rs10485057, and rs511420 have fewer symptoms in low stress conditions but more symptoms in high stress conditions compared to major allele homozygotes. LIMITATIONS The genetic variants associated with depression in African American adolescents may not translate to other ethnic groups. This study is also limited in that only one gene that functions within a complex biological system is addressed. CONCLUSIONS This current study is the first to find an interaction between OPRM1 and life stress that is associated with depression. It also addressed an understudied population within the behavioral genetics literature. Further research should test additional genes involved in the opioid system and expand the current findings to more diverse samples.

Effect of Pet Dogs on Children's Perceived Stress and Cortisol Stress Response

The present study tested whether pet dogs have stress-buffering effects for children during a validated laboratory-based protocol, the Trier Social Stress Test for Children (TSST-C). Participants were 101 children aged 7-12 years with their primary caregivers and pet dogs. Children were randomly assigned in the TSST-C to a pet present condition or one of two comparison conditions: parent present or no support figure present. Baseline, response, and recovery indices of perceived stress and cortisol levels were computed based on childrens self-reported feelings of stress and salivary cortisol. Results indicated that in the alone (no social support) condition, children showed the expected rise for both perceived stress and cortisol response to stress. Pet dog presence significantly buffered the perceived stress response in comparison to children in the alone and parent present conditions. No main condition effect was observed for cortisol; however, for children experiencing the stressor with their pet present, lower cortisol response to stress was associated with more child-initiated petting and less dog proximity-seeking behavior. The results support the notion that pet dogs can provide socio-emotional benefits for children via stress buffering.