Cortisol in early childhood moderates the association between family routines and observed affective balance in children from low-income backgrounds.

The study of emotion regulation often addresses control of negative emotion. Researchers have proposed that affective balance is an indicator of emotion regulation that incorporates the role of positive emotion in the context of negative emotional experiences. Environmental and individual factors, such as family processes and biological stress regulation, are known to shape emotion regulation. The present study investigated whether child diurnal cortisol, an indicator of biological stress regulation, moderated the association between family routines and observed affective balance. Children (N = 222; M age = 4.70 years, SD = 0.60) from low-income households provided saliva samples to measure diurnal cortisol and completed a behavioral task designed to elicit negative emotions. Affective balance was defined as the difference score between the proportion of positive and negative emotional expressions displayed during the task. A higher affective balance score indicated greater positive compared with negative emotional displays. Simple slope analyses indicated that for children with a low morning cortisol intercept, more frequent family routines were associated with more affective balance. This pattern was not observed in children with average or high morning cortisol. Positive family routines may play an important role in shaping affective balance among children with disrupted cortisol levels from low-income backgrounds.

Longitudinal associations between overweight/obesity and stress biology in low-income children.

BACKGROUND/OBJECTIVES: Associations between overweight and altered stress biology have been reported cross-sectionally during childhood, but it is unclear whether overweight precedes altered stress biology or if altered stress biology predicts greater likelihood of overweight over time. The current longitudinal study investigates associations between overweight/obesity, salivary alpha amylase and cortisol morning intercept, diurnal slope, and reactivity to social stress in a cohort of low-income children during preschool and middle childhood. SUBJECTS/METHODS: Children were recruited through Head Start and were observed and followed into middle childhood (N = 257; M = 8.0 years). Height and weight were measured at both time points. Saliva samples were collected across the day and in response to a social challenge at both ages for alpha amylase and cortisol determination. RESULTS: Cross-lagged panel analyses indicated that overweight/obesity at preschool predicted lower morning alpha amylase (ß = -0.18, 95% CI: -0.34, -0.03; p = 0.023), lower morning cortisol (ß = -0.22, 95% CI: -0.38, -0.06; p = 0.006), lower sAA diurnal slope (ß = -0.18, 95% CI: -0.34, -0.03; p = 0.021), and lower cortisol stress reactivity (ß = -0.19, 95% CI: -0.35, -0.02; p = 0.031) in middle childhood. Lower alpha amylase reactivity at preschool was the only biological factor that predicted higher likelihood of overweight/obesity at middle childhood (ß = -0.20, 95% CI: -0.38, -0.01; p = 0.035). CONCLUSIONS: These findings suggest that overweight/obesity may be driving changes in stress biology across early-to-middle childhood, particularly in downregulation of morning levels of stress hormones, diurnal sAA slope, and cortisol reactivity to stress, rather than stress biology driving overweight/obesity.

Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines.

BACKGROUND: Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. METHODS: This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20 weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. RESULTS: We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. CONCLUSIONS: Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. TRIAL REGISTRATION: Clinical Trial Registration: registration number NCT00711971 7/7/2008.

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.

Family conflict, chaos, and negative life events predict cortisol activity in low-income children.

Childhood poverty is hypothesized to increase risk for mental and physical health problems at least in part through dysregulation of the hypothalamic-pituitary-adrenal axis. However, less is known about the specific psychosocial stressors associated with cortisol reactivity and regulation for children living in poverty. The current study investigates negative life events, household chaos, and family conflict in preschool and middle childhood as potential predictors of cortisol regulation in low-income 7-10 year olds (N = 242; M age = 7.9 years). Participants were assessed in preschool and participated in a follow-up assessment in middle childhood, during which diurnal free cortisol and free cortisol reactivity to the Trier Social Stress Test for Children (TSST-C) were assessed. Household chaos during preschool predicted a more blunted diurnal cortisol slope in middle childhood. Greater negative life events during preschool and greater concurrent family conflict were associated with increased free cortisol reactivity in middle childhood.

Child cortisol moderates the association between family routines and emotion regulation in low-income children.

Biological and social influences both shape emotion regulation. In 380 low-income children, we tested whether biological stress profile (cortisol) moderated the association among positive and negative home environment factors (routines; chaos) and emotion regulation (negative lability; positive regulation). Children (M age = 50.6, SD = 6.4 months) provided saliva samples to assess diurnal cortisol parameters across 3 days. Parents reported on home environment and child emotion regulation. Structural equation modeling was used to test whether cortisol parameters moderated associations between home environment and child emotion regulation. Results showed that home chaos was negatively associated with emotion regulation outcomes; cortisol did not moderate the association. Child cortisol level moderated the routines-emotion regulation association such that lack of routine was most strongly associated with poor emotion regulation among children with lower cortisol output. Findings suggest that underlying child stress biology may shape response to environmental influences.

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study.

BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. METHODS: This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36 weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N = 117) and 34-36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20 weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks' gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER: NCT00711971.

Population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

OBJECTIVES: To determine the population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants receiving IV hydrocortisone for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability. DESIGN: Prospective observational cohort study. SETTING: Level 3 neonatal ICU. PATIENTS: Sixty-two critically ill neonates and infants receiving IV hydrocortisone as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23-41), median weight 1.2 kg (range, 0.5-4.4), and 29 females. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Unbound baseline cortisol and postdose hydrocortisone concentrations measured from blood samples being drawn for routine laboratory tests. A one-compartment model best described the data. Allometric weight and postmenstrual age were significant covariates on unbound hydrocortisone clearance and volume of distribution. Final population estimates for clearance, volume of distribution, and baseline cortisol concentration were 20.2 L/hr, 244 L, and 1.37 ng/mL, respectively. Using the median weight and postmenstrual age of our subjects (i.e., 1.2 kg and 28 wk) in the final model, the typical unbound hydrocortisone clearance and volume of distribution were 1.0 L/hr and 4.2 L, respectively. The typical half-life for unbound hydrocortisone was 2.9 hours. A sharp and continuous increase in unbound hydrocortisone clearance was observed at 35 weeks postmenstrual age. CONCLUSIONS: We report the first pharmacokinetic data for unbound hydrocortisone, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound hydrocortisone clearance increased with body weight and was faster in children with an older postmenstrual age. Unbound hydrocortisone clearance increased sharply at 35 weeks postmenstrual age and continued to mature thereafter. This study lays the groundwork for evaluating unbound hydrocortisone exposure-response relationships and drawing definitive conclusions about the dosing of IV hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

Representativeness of obstetric patients who participate in perinatal depression research: findings from the Women's Mental Health and Infants Program (WMHIP) integrated dataset.

The aims of this study were to evaluate the feasibility of integrating archival datasets from depression projects involving pregnant women recruited from obstetric clinics and then assess the representativeness of the integrated dataset. Datasets from six studies were standardized and integrated. Chi-square, t-, and Wilcoxon rank-sum tests were used to compare characteristics between women who completed a depression screening questionnaire (DSQ) and were (1) eligible and ineligible for research participation and (2) eligible women who accepted and declined participation. The integrated dataset comprises 9,112 pregnant women, of whom 71.0 % (n = 6,472) were ineligible for participation because their DSQ scores indicated no-to-minimal depressive symptoms (NDS). Among the 23.9 % (2,176) of women identified as eligible, in part, because their DSQ scores indicated elevated levels of depressive symptoms (EDS), 29.6 % (644) of women participated (P-EDS) and 47.6 % (1,036) of women did not participate (D-EDS). While the NDS and EDS groups were significantly different on almost all variables, the P-EDS and D-EDS groups were significantly different on only a few variables. Compared to the D-EDS group, the P-EDS group was earlier in pregnancy and, on the Edinburgh Postnatal Depression Screen, was more likely to endorse impaired "ability to laugh" and "enjoy oneself", and endorse at greater severity "ability to laugh." It is a reasonable and feasible strategy to integrate thematically similar datasets to increase statistical power. Additionally, typical recruitment strategies for minimal risk perinatal depression research at obstetric clinics, during routine prenatal care visits, appear to produce an externally valid study cohort.

Diurnal cortisol pattern, eating behaviors and overweight in low-income preschool-aged children.

This study examined, among children, the associations among chaos in the home, diurnal cortisol patterns, eating behaviors and being overweight. Participants included 331 low-income children aged 3-4years. Mean salivary cortisol-intercept (representing morning peak, 60min since waking) and cortisol-slope (representing diurnal decline after peak) were calculated using mixed models from samples obtained across 3days. Parents reported chaos in the home by questionnaire and responded to the Children's Eating Behavior Questionnaire, generating subscales Food Responsiveness (FR), Emotional Overeating (EO), Enjoyment of Food (EF), and Satiety Responsiveness (SR). Body mass index was categorized as overweight vs. not. Path analysis evaluated associations among chaos, cortisol patterns, eating behaviors, and weight status. Children living in more chaotic homes had lower morning cortisol levels, consistent with "hypocortisolism" reported among individuals who have experienced significant allostatic load as a result of substantial early life chronic stress. Among girls, the hypocortisolism pattern predicted a higher likelihood of being overweight both directly and mediated through reduced Satiety Responsiveness; in boys, the association of the hypocortisolism pattern with being overweight was mediated entirely through Emotional Overeating. In summary, our results provide support for the conceptual model that psychosocial stress contributes to hypocortisolism, which contributes directly to a higher likelihood of being overweight in girls, and indirectly through reduced Satiety Responsiveness in girls and through increased Emotional Overeating in boys.

Severe hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in a 16 year old African-American male.

Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies (IAb). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African-American adolescent. A 16-yr-old healthy African-American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio-ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia.

The mothers, Omega-3 and mental health study.

BACKGROUND: Major depressive disorder (MDD) during pregnancy and postpartum depression are associated with significant maternal and neonatal morbidity. While antidepressants are readily used in pregnancy, studies have raised concerns regarding neurobehavioral outcomes in exposed infants. Omega-3 fatty acid supplementation, most frequently from fish oil, has emerged as a possible treatment or prevention strategy for MDD in non-pregnant individuals, and may have beneficial effects in pregnant women. Although published observational studies in the psychiatric literature suggest that maternal docosahexaenoic acid (DHA) deficiency may lead to the development of MDD in pregnancy and postpartum, there are more intervention trials suggesting clinical benefit for supplementation with eicosapentaenoic acid (EPA) in MDD. METHODS/DESIGN: The Mothers, Omega-3 and Mental Health study is a double blind, placebo-controlled, randomized controlled trial to assess whether omega-3 fatty acid supplementation may prevent antenatal and postpartum depressive symptoms among pregnant women at risk for depression. We plan to recruit 126 pregnant women at less than 20 weeks gestation from prenatal clinics at two health systems in Ann Arbor, Michigan and the surrounding communities. We will follow them prospectively over the course of their pregnancies and up to 6 weeks postpartum. Enrolled participants will be randomized to one of three groups: a) EPA-rich fish oil supplement (1060 mg EPA plus 274 mg DHA) b) DHA-rich fish oil supplement (900 mg DHA plus 180 mg EPA; or c) a placebo. The primary outcome for this study is the Beck Depression Inventory (BDI) score at 6 weeks postpartum. We will need to randomize 126 women to have 80% power to detect a 50% reduction in participants' mean BDI scores with EPA or DHA supplementation compared with placebo. We will also gather information on secondary outcome measures which will include: omega-3 fatty acid concentrations in maternal plasma and cord blood, pro-inflammatory cytokine levels (IL-1ß, IL-6, and TNF-α) in maternal and cord blood, need for and dosage of antidepressant medications, and obstetrical outcomes. Analyses will be by intent to treat. DISCUSSION: This study compares the relative effectiveness of DHA and EPA at preventing depressive symptoms among pregnant women at risk. CLINICAL TRIAL REGISTRATION NUMBER: NCT00711971.

Adrenocortical response in infants undergoing cardiac surgery with cardiopulmonary bypass and circulatory arrest.

OBJECTIVE: To detail changes in adrenocorticotropic hormone (ACTH), cortisol, and aldosterone levels following cardiac surgery and to test the hypothesis that postcardiotomy infants requiring excessively high-dose vasopressor support will demonstrate adrenal insufficiency which will be proportional to cardiopulmonary bypass (CPB)/circulatory arrest times and vasopressor requirements. DESIGN: Prospective observational pilot study. SETTING: A tertiary care pediatric cardiac intensive care unit. PATIENTS: Prospectively enrolled infants were divided into three subgroups: CPB, CPB with deep hypothermic circulatory arrest (DHCA), and control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A representative patient sample from each surgical group underwent preoperative synthetic ACTH testing. Postoperative serum samples for cortisol, ACTH, and inotrope score (IS) were collected at discrete intervals over 48 hrs along with patient demographics, surgical procedure, and CPB/DHCA times. Fifty-eight patients were classified by subgroup: 31 CPB, 22 DHCA, and 5 controls. Ten patients with DHCA, analyzed separately, received intraoperative steroids. Tested patients demonstrated preoperative adrenal competence. Cortisol peaked within 2 hrs of surgery without differences among groups. ACTH inversely correlated with bypass time in patients with DHCA (p = .03) but not with circulatory arrest time. Peak cortisol level did not correlate with simultaneous IS. Although not noted in any DHCA-steroid patients, nine patients had increased ACTH/cortisol ratios in association with elevated ISs suggesting inadequate adrenal responsiveness to endogenous ACTH. CONCLUSIONS: The majority of infants with congenital heart disease and intact hypothalamic-pituitary-adrenal axes demonstrated an appropriate adrenocortical stress response to cardiac surgery. Peak serum cortisol was unrelated to CPB/DHCA time and did not predict the level of inotrope support. However, a subset of patients with elevated ACTH/cortisol ratios seemed to have a clinical status consistent with adrenal insufficiency and may be a target group for early postoperative steroid therapy.

Developmental programming: Prenatal bisphenol A treatment disrupts mediators of placental function in sheep.

Gestational Bisphenol A (BPA) exposure is associated with low birth weight. We hypothesized that the low birth weight is the consequence of reduced placental efficiency and a function of BPA-induced inflammatory, oxidative, lipotoxic, angiogenic, steroidal and fibrotic changes involving epigenetic alterations. Placentomes were collected during early (day 65) and mid (day 90) gestation (term ∼147 days) from control and BPA (gestational day 30-90)-treated pregnant sheep. BPA treatment: reduced placental efficiency and fetal weight; increased interleukin 8, lipid peroxidation marker, antioxidants, aromatase, 17 alpha-hydroxylase, estrogen receptor 2, insulin like growth factor (IGF) 2 receptor and IGF binding proteins (IGFBP), and histone deacetylase 1 and 2; reduced tumor necrosis factor alpha and IGF1 receptor at early gestation (Day 65). Gestational BPA-induced mid-gestational changes include: reduced angiogenic factor hypoxia inducible factor 1 alpha; increased IL1beta, oxidative stress markers, triglyceride, 17alpha hydroxylase, IGFBP 1, DNA methyltransferase 3 A and histone deacetylase 1. These findings indicate that gestational BPA, either acting directly or by altering steroidal input, produces early/mid-gestational-specific epigenetic changes culminating in placental disruptions at several levels, in keeping with time-specific/time-lagged pregnancy-associated changes in placental efficiency and fetal weight. The reduced early-gestational placental efficiency may be a function of increased inflammation/oxidative stress and reduced IGF bioavailability with the mid-gestational restoration of placental efficiency likely driven by improved IGF bioavailability and the time-lagged response to antioxidant increase. This compensation, the result of time-lagged response to increases in negative mediators of placental function must have failed with pregnancy advancement to explain the low birthweight outcome.

Early developmental changes in sleep in infants: the impact of maternal depression.

OBJECTIVES: This study evaluated whether sleep over the first 6 months of life was more disturbed in infants born to mothers who were depressed compared with infants from nondepressed mothers. DESIGN: Actigraphy was recorded for 7 consecutive days starting at 2 weeks postpartum and monthly thereafter until 6 months of age. Mothers completed daily sleep/wake diaries. Sleep data at 2 weeks and 6 months postpartum are presented here. SETTING: The home environment. PARTICIPANTS: Eighteen healthy, full-term infants, 9 males and 9 females. Seven infants were born to women with no personal or family history of depression; 11 infants were born to women diagnosed with depression or with elevated levels of depression symptoms. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Total sleep time, sleep latency, sleep efficiency, and number and duration of sleep episodes were computed for nocturnal and daytime sleep in each 24-hour block. Data were coded for risk group (1 = low risk, 2 = high risk), and repeated-measures multivariate analysis of variance contrasted changes in sleep measures at Week 2 and Week 24, between risk groups. The high-risk infants took longer to fall asleep, had lower sleep efficiencies, and had more sleep bouts in the nocturnal sleep period than did low-risk infants. These effects persisted at 6 months postpartum. CONCLUSIONS: Maternal depression is associated with significant sleep disturbance in infancy at 2 weeks postpartum that continues through 24 weeks. It remains to be determined if sleep disturbance in infancy confers a greater risk of developing early-onset depression in childhood.

Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation.

Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. We report a patient with permanent neonatal diabetes mellitus and severe exocrine pancreatic insufficiency. Ultrasound examination revealed pancreatic agenesis with a suggestion of a small amount of tissue in the head of the pancreas. Genetic testing revealed that the neonate had a homozygous Pro63fsX60 IPF-1 mutation. This is the second reported case of neonatal diabetes mellitus secondary to a homozygous mutation in the IPF-1 gene and supports the previously proposed biological role of IPF-1 in the pancreatic development in human.

Individual differences in cortisol responses to fear and frustration during middle childhood.

The purpose of this study was to examine individual differences in the activation and regulation of the hypothalamic-pituitary-adrenal (HPA) axis in prepubertal children after exposure to two different stress modalities and to evaluate the utility of an individual differences approach to the examination of HPA axis functioning. After a 30-min controlled baseline period, 73 7-year-olds (40 boys and 33 girls) were randomly assigned to a validity check condition or one of two experimental tasks designed to elicit fear or frustration. This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples were collected, including 12 poststress samples at 5-min intervals. There was a significant stress modality effect, with children exposed to the fear condition reaching peak cortisol levels at 25min poststress and those exposed to the frustration condition reaching peak levels at 45min poststress. There was no difference in peak cortisol levels between the stress modalities. Individual variability across conditions was significant, with participants reaching peak levels as early as 10min poststress and as late as 60min poststress. Our data suggest that analysis of individual curves prior to making group-level comparisons may improve the explanatory power of HPA axis behavior models.

Transcriptional profiling of the developing rat brain reveals that the most dramatic regional differentiation in gene expression occurs postpartum.

Neural development involves the expression of ensembles of regulatory genes that control the coordinate and region-specific expression of a host of other genes, resulting in the unique structure, connectivity, and function of each brain region. Although the role of some specific genes in neural development has been studied in detail, we have no global view of the orchestration of spatial and temporal aspects of gene expression across multiple regions of the developing brain. To this end, we used transcriptional profiling to examine expression levels of 9955 genes in the hypothalamus, hippocampus, and frontal cortex across seven stages of postnatal development and up to four stages of prenatal development in individual male rats (six per group). The results reveal dramatic changes across development in >97% of the neurally expressed genes. They also uncover a surprising degree of regional differentiation occurring after birth and through the first 2 weeks of life. Cluster analysis identifies 20 clusters of transcripts enriched in genes related to particular functions, such as DNA metabolism, nuclear function, synaptic vesicle transport, myelination, and neuropeptide hormone activity. Thus, groups of genes with related functions change in the brain at specific times, possibly marking critical periods for each function. These findings can broadly serve as a backdrop for studying the role of individual genes in neural development. They also underscore the importance of early postnatal life in the rat, which corresponds to late gestation in the human, as a critical late phase of neural organization and differentiation, even in subcortical regions.

Associations between stress biology indicators and overweight across toddlerhood.

Biological stress responses are proposed as a pathway through which stress exposure can "get under the skin" and lead to health problems, specifically obesity. Yet, it is not clear when such associations may emerge or whether they are bidirectional. Cortisol and salivary alpha amylase (sAA) were considered indicators of the biological stress response. We tested the longitudinal association between cortisol and sAA and weight in 215 low-income children at ages 21, 27, and 33 months (52% male; 46% non-Hispanic white). sAA and cortisol intercept and slope (representing morning level and rate of change across the day) were calculated for each age point using random effect models. Children were weighed and length measured and categorized as overweight versus normal weight (overweight defined as weight-for-length z-score ≥85th percentile for age and sex). Cross-lagged models stratified by sex and controlling for birthweight z-score tested the concurrent and cross-lagged associations between each of 4 indices of stress biology individually (cortisol and sAA intercept and slope) and overweight. Overweight status was correlated across time. Cortisol and sAA were correlated across occasions of measurement, though somewhat less strongly in boys. There were no concurrent associations between stress indicators and overweight. sAA at 27 months predicted greater risk of overweight at 33 months in girls, such that both lower sAA intercept and more rapidly increasing sAA at 27 months predicted greater risk of overweight at 33 months (ß=-0.64, p<0.05 and ß=1.09, p<0.05, respectively). For boys only, overweight at 21 months predicted lower sAA intercept at 27 months (ß=-0.35, p<0.05). Findings suggest that longitudinal associations of stress biology and weight status may be present only on a limited basis very early in the lifespan.

Saliva cortisol and response to dexamethasone in children of depressed parents.

BACKGROUND: Major depression (MDD) is heritable, and children of depressed parents are at higher risk for the development of depression. However, depression in a parent might also act as a stressor leading to increased activation of neuroendocrine stress circuits. To address this question we examined saliva cortisol in children whose parents have a history of MDD. METHODS: We recruited 15 families with one parent with MDD (26 prepubertal children) and 16 control families without history of parental MDD (32 prepubertal children). All parents and children underwent Structured Clinical Interview for DSM-IV and Kiddie Schedule For Affective Disorders And Schizophrenia interviews, respectively. Families were asked to collect morning, afternoon, and bedtime saliva samples for 4 days for 2 weeks. At bedtime of the 3rd day, dexamethasone was administered. Two doses, standard and low, were used in each family. RESULTS: The majority of children demonstrated no psychiatric diagnosis. Children with MDD parents showed higher cortisol basally and higher cortisol after both 25 mg and 5 mg dexamethasone. However, this effect occurred predominantly in children whose parents were currently depressed. There were strong correlations for cortisol between parents and children (r = 52 in depressed; r = 499 in control). CONCLUSIONS: Elevated cortisol and impaired feedback seemed to reflect an environmental effect of MDD in a parent.