Dehydroepiandrosterone at birth: Response to stress and relation to demographic, pregnancy and delivery factors.

Enhanced production of dehydroepiandrosterone (DHEA) by the foetal hypothalamic-pituitary-adrenal (HPA) axis enables maturational events critical for labour induction and neonatal adaptation. Despite knowledge of the interconnected nature of maternal and foetal physiology and dramatic changes in DHEA production after birth, few studies have examined DHEA levels in newborns and none have examined DHEA's response to acute stress. Understanding normative patterns of early DHEA activity is needed to accurately assess functioning of the biological stress system with relevance for health and development. The present study analysed DHEA concentrations and change after stress among 93 newborns and associations with pregnancy, delivery and demographic risk factors. Three saliva samples, collected prior to and following a blood draw stressor, were used to determine baseline and stress reactive DHEA levels. Mothers self-reported on health behaviours during pregnancy. Data on obstetric factors were obtained from medical records. DHEA levels declined from pre- to post-stressor assessments. Results also showed that post-stressor DHEA change was significantly associated with administration of medications used to treat pain and accelerate labour. However, there was no significant variation in DHEA pre-stress levels or change after stress as a function of time after birth. By capturing DHEA levels after birth, the present study provides a window into prenatal health of the HPA system. The study also advances knowledge of DHEA in newborns by providing data on reference levels and important covariates. This information on basic adrenal physiology provides a foundation that can be expanded on to enhance understanding of early hypothalamic-pituitary-adrenal axis activity.

The impact of maternal stress on infant alpha-amylase is buffered by high infant regulation and low infant negative reactivity.

This study examined the main and interactive effects of maternal perceived stress and infant temperament-surgency, negative affectivity, and orienting/regulation-on infant salivary alpha-amylase (sAA) responses to stress. Saliva samples were collected prior to and following two naturalistic stressors: maternal separation conducted at 9 months and blood draw/immunizations conducted at 12 months. sAA area under the curve (AUC) was computed to determine response of the sympathetic nervous system to each stressor. Results revealed significant interactions of maternal stress and infant negative affectivity and orienting/regulation with sAA AUC. Relations between maternal stress and infant sAA AUC were stronger among infants with higher levels of negative affectivity and lower levels of orienting/regulation. These results highlight the need to examine both infant characteristics and environmental factors when investigating the development of stress response systems.

Putting a finger on the problem: Finger stick blood draw and immunization at the well-child exam elicit a cortisol response to stress among one-year-old children.

Research examining stress reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis in young children has historically been hampered by a lack of reliable methods to invoke a cortisol stress response. This report details an effective method of eliciting a cortisol rise in one-year-old children (N = 83) by modifying and combining two naturalistic stressors previously used with infants and children. Salivary cortisol levels were collected from children before and after a finger stick blood draw and immunizations performed during their one year well-child checkup at their pediatrician's office. Results indicated that the stressor was successful at eliciting a significant cortisol response. An extensive set of potential demographic and clinical confounds were also assessed in order to identify methodological considerations important in studies of infant cortisol. The stress paradigm presented here provides a promising alternative for studies of infant HPA activity to enable investigators to more effectively evaluate early functioning of the biological stress system during this developmentally important life stage.

BNDF methylation in mothers and newborns is associated with maternal exposure to war trauma.

BACKGROUND: The BDNF gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters BDNF methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and BDNF methylation in humans. This study examined associations of prenatal exposure to maternal stress and BDNF methylation at CpG sites across the BDNF gene. RESULTS: Among 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and BDNF methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions. CONCLUSIONS: This is the first study in humans to examine BDNF methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and BDNF methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth.

Cortisol and DHEA in development and psychopathology.

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.

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.

Using a Brief Parent-Report Measure to Track Outcomes for Children and Teens with Internalizing Disorders.

The Pediatric Symptom Checklist (PSC) is a widely-used, parent-completed measure of children's emotional and behavioral functioning. Previous research has shown that the PSC and its subscales are generally responsive to patient progress over the course of psychiatric treatment. In this naturalistic study, we examined the performance and utility of the five-item PSC Internalizing Subscale (PSC-IS) as an assessment of routine treatment in outpatient pediatric psychiatry. Parents and clinicians of 1,593 patients aged 17 or younger completed standardized measures at intake and three-month follow-up appointments. Comparisons between PSC-IS scores and clinician-reported diagnoses, internalizing symptoms, and overall functioning showed acceptable levels of agreement. Change scores on the PSC-IS were also larger among patients with internalizing diagnoses than those with non-internalizing diagnoses. As a brief measure of internalizing symptoms, the PSC may be particularly useful to mental health clinicians treating youth with depression and anxiety as a quality assurance or treatment outcome measure.

Have rates of behavioral health assessment and treatment increased for Massachusetts children since the Rosie D. decision? A report from two primary care practices.

Following a court decision (Rosie D. v. Romney), the Medicaid program in Massachusetts launched the statewide Children's Behavioral Health Initiative in 2008 to increase the recognition and treatment of behavioral health problems in pediatrics. We reviewed billing data (n = 64,194) and electronic medical records (n = 600) for well child visits in pediatrics in 2 practices to examine rates of behavioral health screening, problem identification, and treatment among children seen during the year before and 2 years after the program's implementation. According to electronic medical records, the percentage of well child visits that included any form of behavioral health assessment increased significantly during the first 2 years of the program, and pediatricians significantly increased their use of standardized screens. According to billing data, behavioral health treatment increased significantly. These findings suggest that behavioral health screening and treatment have increased following the Rosie D. decision.

National quality measures for child mental health care: background, progress, and next steps.

OBJECTIVE: To review recent health policies related to measuring child health care quality, the selection processes of national child health quality measures, the nationally recommended quality measures for child mental health care and their evidence strength, the progress made toward developing new measures, and early lessons learned from these national efforts. METHODS: Methods used included description of the selection process of child health care quality measures from 2 independent national initiatives, the recommended quality measures for child mental health care, and the strength of scientific evidence supporting them. RESULTS: Of the child health quality measures recommended or endorsed during these national initiatives, only 9 unique measures were related to child mental health. CONCLUSIONS: The development of new child mental health quality measures poses methodologic challenges that will require a paradigm shift to align research with its accelerated pace.