Jenalee R. Doom

Stress physiology and developmental psychopathology: Past, present, and future

Research on the hypothalamic-pituitary-adrenocortical (HPA) axis has emerged as a vital area within the field of developmental psychopathology in the past 25 years. Extensive animal research has provided knowledge of the substrates and physiological mechanisms that guide development of stress reactivity and regulation using methods that are not feasible in humans. Recent advances in understanding the anatomy and physiology of the HPA axis in humans and its interactions with other stress-mediating systems, including accurate assessment of salivary cortisol, more sophisticated neuroimaging methods, and a variety of genetic analyses, have led to greater knowledge of how psychological and biological processes impact functioning. A growing body of research on HPA axis regulation and reactivity in relation to psychopathology has drawn increased focus on the prenatal period, infancy, and the pubertal transition as potentially sensitive periods of stress system development in children. Theories such as the allostatic load model have guided research by integrating multiple physiological systems and mechanisms by which stress can affect mental and physical health. However, almost none of the prominent theoretical models in stress physiology are truly developmental, and future work must incorporate how systems interact with the environment across the life span in normal and atypical development. Our theoretical advancement will depend on our ability to integrate biological and psychological models. Researchers are increasingly realizing the importance of communication across disciplinary boundaries in order to understand how experiences influence neurobehavioral development. It is important that knowledge gained over the past 25 years has been translated to prevention and treatment interventions, and we look forward to the dissemination of interventions that promote recovery from adversity.

Child maltreatment and gender interactions as predictors of differential neuroendocrine profiles

Child maltreatment is a potent stressor associated with neuroendocrine dysregulation and increased risk for mental and physical disorders throughout the lifespan. Gender differences in stress reactivity and adult psychopathology prevalence may be related to sex-specific responsivity to stress. The purpose of this study is to examine whether gender interacts with the stress of maltreatment to produce differential neuroendocrine profiles in children. Participants included 137 maltreated and 110 nonmaltreated low-income, racially and ethnically diverse children (range: 7.9-10.9 years; M=9.42 years; 52% male) who attended a summer research day camp. Saliva was collected 3 times across the day for 5 days for cortisol and dehydroepiandosterone (DHEA) analysis. Department of Human Services records were examined to determine the type, severity, chronicity, onset, and recency of maltreatment for children in the maltreated group. Significant interactions between gender and maltreatment pervasiveness predicted diurnal cortisol, DHEA, and cortisol/DHEA ratio levels. Elevated daily cortisol levels were reported for boys compared to girls in the group with more pervasive maltreatment. Boys with less pervasive maltreatment had lower DHEA and higher cortisol/DHEA ratio levels than girls with similar experiences, nonmaltreated boys, and boys with more pervasive maltreatment. Further results are consistent with down-regulation of cortisol production in girls with more pervasive maltreatment and girls who experienced maltreatment that was early onset and not recent. The effectiveness of interventions for maltreated children may be improved with greater knowledge of how maltreatment differentially affects neuroendocrine regulation by gender.

Striking while the iron is hot: Understanding the biological and neurodevelopmental effects of iron deficiency to optimize intervention in early childhood.

Prenatal and early postnatal iron deficiency (ID) is associated with long-term neurobiological alterations and disruptions in cognitive, social, and behavioral development. Early life ID is particularly detrimental as this is a period of rapid neurodevelopment. Even after iron supplementation, cognitive and social disruptions often persist in formerly iron-deficient individuals. Observational studies of the acute and long-term effects of early life ID yield different results based on the timing of ID. Further, intervention studies demonstrate some improvement for certain domains but still show residual effects years later, which are dependent on the timing of ID and treatment. This review will cover the effects of ID during infancy and early childhood on brain structure and function, cognition, and behavior in relation to preclinical models of ID and sensitive periods of human brain development.

Beyond Stimulus Deprivation: Iron Deficiency and Cognitive Deficits in Postinstitutionalized Children

Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on cognitive functioning in children adopted from institutions between 17 and 36 months of age were examined. ID was assessed in 55 children soon after adoption, and cognitive functioning was evaluated 11-14.6 months postadoption when the children averaged 37.4 months old (SD = 4.9). ID at adoption and longer duration of institutional care independently predicted lower IQ scores and executive function (EF) performance. IQ did not mediate the association between ID and EF.

Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity

Internationally adopted adolescents who are adopted as young children from conditions of poverty and deprivation have poorer physical and mental health outcomes than do adolescents conceived, born, and raised in the United States by families similar to those who adopt internationally. Using a sample of Russian and Eastern European adoptees to control for Caucasian race and US birth, and nonadopted offspring of well-educated and well-resourced parents to control for postadoption conditions, we hypothesized that the important differences in environments, conception to adoption, might be reflected in epigenetic patterns between groups, specifically in DNA methylation. Thus, we conducted an epigenome-wide association study to compare DNA methylation profiles at approximately 416,000 individual CpG loci from peripheral blood mononuclear cells of 50 adopted youth and 33 nonadopted youth. Adopted youth averaged 22 months at adoption, and both groups averaged 15 years at testing; thus, roughly 80% of their lives were lived in similar circumstances. Although concurrent physical health did not differ, cell-type composition predicted using the DNA methylation data revealed a striking difference in the white blood cell-type composition of the adopted and nonadopted youth. After correcting for cell type and removing invariant probes, 30 CpG sites in 19 genes were more methylated in the adopted group. We also used an exploratory functional analysis that revealed that 223 gene ontology terms, clustered in neural and developmental categories, were significantly enriched between groups.

The roles of puberty and age in explaining the diminished effectiveness of parental buffering of HPA reactivity and recovery in adolescence

Parental support is a powerful regulator of stress and fear responses for infants and children, but recent evidence suggests it may be an ineffective stress buffer for adolescents. The mechanisms underlying this developmental shift are not well-understood. The goal of the present study was to examine the independent and joint contributions of pubertal status and chronological age in explaining this shift. A sample of 75 typically developing youth (M age=12.95 years, SD=0.70, range=11.7-14.6 years; 37 females) was recruited to complete a modified Trier Social Stress Test (TSST-M) in the laboratory. Participants were recruited in such a way as to disentangle pubertal stage and chronological age by phone screening for markers of pubertal stage and then recruiting roughly equal numbers of younger and older, pre/early and mid/late pubertal youth who were then randomly assigned within groups to condition. The TSST-M was used as the stressor and youth prepared either with their parent or stranger (parent condition: N=39). Pubertal stage was confirmed by the Petersen Pubertal Development Scale at the time of testing and treated, along with chronological age, as a continuous variable in the analyses. The results revealed an interaction of pubertal stage and support condition for cortisol reactivity to the TSST-M such that preparing for the speech with the parent became a less potent buffer of the HPA axis as pubertal stage increased. Age did not interact with condition in predicting cortisol reactivity. In contrast, the parents presence during speech preparation decreased in its effectiveness to hasten recovery of the HPA axis as children got older, but pubertal stage was not predictive of recovery rate. These patterns were specific to cortisol and were not observed with salivary alpha-amylase levels or subjective stress ratings for the task. These analyses suggest that the switch away from using parents as social buffers may be the result of neurobiological mechanisms associated with puberty.

Social stress buffering by friends in childhood and adolescence: Effects on HPA and oxytocin activity

ABSTRACT Previous research has demonstrated that before puberty, parents are able to buffer, and often completely block, cortisol responses to social evaluative stressors (e.g., Trier Social Stress Test; TSST). However, after puberty, parents no longer provide a powerful buffer of the HPA axis from a social-evaluative stressor. The current study investigates whether friends can buffer the HPA axis in both children and adolescents compared to parents and whether similar stress-ameliorating patterns can also be observed in oxytocin activity. A total of 109 participants (54 children aged 9–10 and 55 adolescents aged 15–16; half of each sex) completed the TSST and were randomly assigned to prepare for their speech with their parent or friend for 5 minutes beforehand. Salivary cortisol and urinary oxytocin were measured before and after the TSST. For children, cortisol responses were comparable regardless of who helped the child prepare the speech. For adolescents, however, friends actually amplified the cortisol response compared to parents. In addition, adolescents produced less oxytocin than children, as did males compared to females. Notably, for boys, oxytocin levels decreased across the session if participants prepared with a friend rather than their parent. The mean change was in the same direction but not significant for girls. These results indicate that friends do not take over the social buffering role by age 15–16, which may inform interventions in at-risk children and adolescents.

Maternal relationship during adolescence predicts cardiovascular disease risk in adulthood.

OBJECTIVE The current study investigated whether greater maternal support during adolescence is associated with lower levels of cardiovascular disease (CVD) risk in adulthood, and whether maternal support serves as a moderator or a mediator of the socioeconomic status (SES) and CVD risk association. In addition, potential moderators and mediators of the association between adult CVD risk and adolescent maternal support and SES were tested. METHOD Using the National Longitudinal Study of Adolescent to Adult Health (n = 11,013), we examined relations between maternal support during adolescence (M = 15.3 years) and CVD risk in young adulthood (M = 28.7 years) via path analysis. Maternal support was assessed by a composite of adolescent and mother report. CVD risk was calculated with a Framingham-based prediction model that uses age, sex, body mass index, smoking, systolic blood pressure, diabetes, and use of antihypertensive medication. RESULTS Greater maternal support in adolescence was related to lower CVD risk in young adulthood (B = -0.56, 95% CI: -0.91 to -0.20, p < .01). The interaction between adolescent SES and maternal support was not significant, (p > .05), but there was an interaction between maternal support and race such that African American adolescents were more sensitive than Whites to the effects of maternal support on CVD risk (B = -0.90, 95% CI: -1.56, -0.25, p < .01). In addition, there was no evidence that maternal support mediated the association between SES and CVD risk (p > .05), and there was no association between SES and maternal support (p > .05), adjusting for confounders. However, the relations of adolescent maternal support and SES to adult CVD risk were mediated by young adult health behaviors and financial stress but not by depressive symptoms. CONCLUSION Greater maternal support during adolescence appears to act independently of SES when impacting CVD risk and may operate through health behaviors and financial stress. (PsycINFO Database Record

Oxytocin and parenting behavior among impoverished mothers with low vs. high early life stress

Recent work suggests that key aspects of sensitive parenting (e.g., warmth, emotional attunement) may be shaped in part by biology, specifically the neuropeptide oxytocin. However, some studies have found that oxytocin may not act in expected ways in higher-risk populations (e.g., those with postnatal depression or borderline personality disorder). This study examined the relation between oxytocin and parenting among mothers with varying levels of early life stress. Forty low-income mothers and their 34- to 48-month-old child participated in this study. Mother-child dyads were observed in an interaction task in their home, and videos of these interactions were later coded for parenting behaviors. Mothers’ oxytocin production before and after the interaction task was assessed through saliva. Mothers’ early stress was assessed via the Adverse Childhood Experiences Scale (ACES; Felitti et al. Am J Prev Med 14:245–258, 1998). For mothers with low ACEs, higher oxytocin secretion was associated with more positive parenting. For mothers with high ACEs, higher oxytocin secretion was associated with lower levels of positive parenting. Oxytocin may be operating differently for mothers who experienced harsh early social environments, supporting more defensive behaviors and harsh parenting than anxiolytic and prosocial behaviors.

Stress in Infancy and Early Childhood: Effects on Development

This article is a revision of the previous edition article by M.R. Gunnar, pp. 12336–12339,