Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months

Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; <or =28 weeks), very low gestational age (VLGA; 29-32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit.

Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

In animal models, variations in early maternal care are associated with differences in hypothalamic-pituitary-adrenal(HPA) stress response in the offspring, mediated via changes in the epigenetic regulation of glucocorticoid receptor (GR) gene (Nr3c1) expression.

Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age

Objective

To examine whether early inflammation is related to cortisol levels at 18 months corrected age (CA) in children born very preterm.

Study Design

Infants born ≤ 32 weeks gestational age were recruited in the NICU, and placental histopathology, MRI, and chart review were obtained. At 18 months CA developmental assessment and collection of 3 salivary cortisol samples were carried out. Generalized least squares was used to analyze data from 85 infants providing 222 cortisol samples.

Results

Infants exposed to chorioamnionitis with funisitis had a significantly different pattern of cortisol across the samples compared to infants with chorioamnionitis alone or no prenatal inflammation (F[4,139] = 7.3996, P <.0001). Postnatal infections, necrotizing enterocolitis and chronic lung disease were not significantly associated with the cortisol pattern at 18 months CA.

Conclusion

In children born very preterm, prenatal inflammatory stress may contribute to altered programming of the HPA axis.

Keywords: preterm, chorioamnionitis, funisitis, premature infants, hypothalamic-pituitary-adrenal axis, infection, cortisol, stress

Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age

Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm =32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-?B, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm. © 2013 Grunau et al.

Plasma cortisol levels and illness appraisal in deficit syndrome schizophrenia

Research investigating the association between negative symptoms and plasma cortisol levels in individuals with schizophrenia has produced inconsistent findings. This study investigated whether deficit syndrome schizophrenia (characterized by high levels of primary negative symptoms) is associated with comparatively high morning plasma cortisol levels, more negative appraisals about illness and higher levels of depression. Participants were 85 individuals diagnosed with schizophrenia and 85 individuals with no history of contact with psychiatric services matched for age and gender. All participants provided fasting 9.00 a.m. plasma cortisol samples. There were no significant differences between the schizophrenia and control participants in plasma cortisol levels. The Proximal Deficit Syndrome method was used to identify individuals with deficit syndrome schizophrenia. Contrary to what had been hypothesized, participants with deficit syndrome schizophrenia had significantly lower plasma cortisol levels than both non-deficit syndrome participants and control participants. Participants with the deficit syndrome reported significantly less negative appraisals about illness (assessed by PBIQ) and lower levels of depression (assessed by BDI-II). Differences in cortisol levels continued to trend toward significance when levels of depression were controlled for. The patterns of illness-related appraisals and plasma cortisol levels raise the possibility that the deficit syndrome could be a form of adaptation syndrome.

Patterns of cortisol and DHEA secretion and relationships with attachment style and psychosocial variables in female adolescents: a developmental psychopathology approach

This programme of research used a developmental psychopathology approach to investigate females across the adolescent period. A two-sided story is presented; first, a study of neuroendocrine and psychosocial parameters in a group of healthy female adolescents (N = 63), followed by a parallel study of female adolescents with anorexia nervosa (AN) (N = 8). A biopsychosocial, multi-method measurement approach was taken, which utilised self-report, interview and hypothalamic-pituitary-adrenocortical (HPA) axis measures. Saliva samples for the measurement of cortisol and DHEA were collected using the best-recommended methodology: multiple samples over the day, strict reference to time of awakening, and two consecutive sampling weekdays. The research was adolescent-orientated: specifically, by using creative and ageappropriate strategies to ensure participant adherence to protocol, as well as more generally by adopting various procedures to facilitate engagement with the research process. In the healthy females mean (± SD) age 13.9 (± 2.7) years, cortisol and DHEA secretion exhibited typical adult-like diurnal patterns. Developmental markers of chronological age, menarche status and body mass index (BMI) had differential associations with cortisol and DHEA secretory activity. The pattern of the cortisol awakening response (CAR) was sensitive to whether participants had experienced first menses, but not to chronological age or BMI. Those who were post-menarche generally reached their peak point of cortisol secretion at 45 minutes post-awakening, in contrast to the pre-menarche group who were more evenly spread. Subsequent daytime cortisol levels were also higher in post-menarche females, and this effect was also noted for increasing age and BMI. Both morning and evening DHEA were positively associated with developmental markers. None of the situational or self-report psychosocial variables that were measured modulated any of the key findings regarding cortisol and DHEA secretion. The healthy group of girls were within age-appropriate norms for all the self-report measures used, however just under half of this group were insecurely attached (as assessed by interview). Only attachment style was associated with neuroendocrine parameters. In particular, those with an anxious insecure style exhibited a higher awakening sample (levels were 7.16 nmol/l, 10.40 nmol/l and 7.93 nmol/l for secure, anxious and avoidant groups, respectively) and a flatter CAR (mean increases over the awakening period were 6.38 nmol/l, 2.32 nmol/l and 8.61 nmol/l for secure, anxious and avoidant groups, respectively). The afore-mentioned pattern is similar to that consistently associated with psychological disorder in adults, and so this may be a pre-clinical vulnerability factor for subsequent mental health problems. A group of females with AN, mean (± SD) age 15.1 (± 1.6) years, were recruited from a specialist residential clinic and compared to the above group of healthy control (HC) female adolescents. A general picture of cortisol and DHEA hypersecretion was revealed in those with AN. The mean (± SD) change exhibited in cortisol levels over the 30 minute post-awakening period was 7.05 nmol/l (± 5.99) and 8.33 nmol/l (± 6.41) for HC and AN groups, respectively. The mean (± SD) evening cortisol level for the HC girls was 1.95 nmol/l (± 2.11), in comparison to 6.42 nmol/l (± 11.10) for the AN group. Mean (± SD) morning DHEA concentrations were 1.47 nmol/l (± 0.85) and 2.25 nmol/l (± 0.88) for HC and AN groups, respectively. The HC group’s mean (± SD) concentration of 12 hour DHEA was 0.55 nmol/l (± 0.46) and the AN group’s mean level was 0.89 nmol/l (± 0.90). This adrenal steroid hypersecretion evidenced by the AN group was not associated with BMI or eating disorder symptomatology. Insecure attachment characterised by fearfulness and anger was most apparent; a style which was unparalleled in the healthy group of female adolescents. The causal directions of the AN group findings remain unclear. Examining some of the participants with AN as case studies one year post-discharge from the clinic illustrated that for one participant who was recovered, in terms of returning to ordinary school life and no longer exhibiting clinical levels of eating disorder symptomatology, her CARs were no longer inconsistent over sampling days and her DHEA levels were also now generally comparable to the healthy control group. For another participant who had not recovered from her AN one year later, the profile of her CAR continued to be inconsistent over sampling days and her DHEA concentrations over the diurnal period were significantly higher in comparison to the healthy control group. In its entirety, this work’s unique contribution lies in its consideration of methodological and developmental issues specifically pertaining to adolescents. Findings also contribute to knowledge of AN and understanding of vulnerability factors, and how these may be used to develop interventions dedicated to improving adolescent health.

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

Indices of post awakening cortisol secretion (PACS), include the rise in cortisol(cortisol awakening response: CAR) and overall cortisol concentrations (e.g. area under the curve with reference to ground: AUCg) in the first 30—45 min. Both are commonly investigated in relation to psychosocial variables. Although sampling within the domestic setting is ecologically valid, participant non-adherence to the required timing protocol results in erroneous measurement of PACS and this may explain discrepancies in the literature linking these measures to trait well-being (TWB). We have previously shown that delays of little over 5 min(between awakening and the start of sampling) to result in erroneous CAR estimates. In this study, we report for the first time on the negative impact of sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to detect significant relationships between PACS and TWB when measured in the domestic setting.Healthy females (N = 49, 20.5 ± 2.8 years) selected for differences in TWB collected saliva samples (S1—4) on 4 days at 0, 15, 30, 45 min post awakening, to determine PACS. Adherence to the sampling protocol was objectively monitored using a combination of electronic estimates of awakening (actigraphy) and sampling times (track caps).Relationships between PACS and TWB were found to depend on sample timing accuracy. Lower TWB was associated with higher post awakening cortisol AUCg in proportion to the mean sample timing accuracy (p < .005). There was no association between TWB and the CAR even taking into account sample timing accuracy. These results highlight the importance of careful electronic monitoring of participant adherence for measurement of PACS in the domestic setting. Mean sample timing inaccuracy, mainly associated with delays of >5 min between awakening and collection of sample 1 (median = 8 min delay), negatively impacts on the sensitivity of analysis to detect associations between PACS and TWB.

Relationship between post-awakening salivary cortisol and melatonin secretion in healthy participants

We report the relationship between patterns of post-awakening salivary melatonin and cortisol secretion in healthy participants (n=51; mean age 21.6 ±5.0 years). Saliva samples were collected within the domestic setting, at 0-, 15-, 30-, and 45-min post-awakening on 2 consecutive typical weekdays. Analyses were undertaken on data with electronically verified sample timing accuracy (55-min delay between awakening and the start of saliva sampling). Melatonin secretion declined linearly by an average of 29% within the first 45-min post-awakening. In contrast, there was a marked 112% surge in cortisol, characteristic of the cortisol awakening response. No day differences in melatonin or cortisol secretion were observed but melatonin concentrations were lower with later awakening. Despite contrasting post-awakening changes in these hormones, there was a lack of relationship between overall levels or patterns of melatonin and cortisol during this period.

Estudo preliminar da variação dos níveis de cortisol em doentes da espécie Canis familiaris sujeitos a mastectomia por doença oncológica da mama

Dissertação de Mestrado Integrado em Medicina Veterinária

Salivary testosterone and cortisol : role of athletic setting, game outcome, and game location /

Many studies investigating the relationship between hormones and competition have focused on athletic competition. The athletic setting enables r researchers to investigate the hormone-behaviour relationship in a relatively controlled environment. However, research to date has been based on observations made from single status contests and/or weekend tournaments and as such, does not provide a clear picture of an individual's average hormonal responses to both victory and defeat. In appreciation of this limitation, the current study tracked elite hockey players throughout a hockey season, measuring pre- and post-game salivary testosterone and Cortisol as well as psychological measures. I was interested in determining whether status outcome (win vs. loss) would influence an individual's testosterone and Cortisol responses to competition. Furthermore, I was also interested in assessing whether testosterone and Cortisol responses were specific to the competitive environment or whether similar hormonal responses would occur during non-competitive practice sessions. Last, I was interested in whether there were any differences in pre-game hormonal and psychological states depending on where the status contest was held: home versus away. The results indicated that game outcome moderated the testosterone responses to competition. That is, testosterone increased significantly more after a victory compared to a defeat. Furthermore, a loss of status produced significantly hreports, the players did not show an anticipatory rise in either Cortisol or testosterone prior to competition. In addition to the effects of status outcome on hormonal levels, it was also found that these hormonal responses were specific to competition. The athletes in the current study did not demonstrate any hormonal responses to the practice sessions. Last, there were significant differences in pre-game testosterone as well as in selfconfidence, cognitive, and somatic anxiety levels depending on the location at which the status contest took place. Pre-game testosterone and self-confidence levels were significantly higher prior to games played in the home venue. In contrast, pre-game somatic and cognitive anxiety levels were significantly higher prior to games played in the away venue. The current findings add to the developing literature on the relationship between hormones and competition. This was the first study to detect a moderating effect of status outcome on testosterone responses in a team sport. Furthermore, this was also the first study in humans to demonstrate that post-contest Cortisol levels were significantly higher after a loss of status. Last, the current study also adds to the sport psychology literature by demonstrating that pre-game psychological variables differ depending on where the status contest is being held: higher self-confidence at home and higher somatic and cognitive anxiety away. Taken together, the results from the current thesis may have important practical relevance to coaches, trainers and sport psychologists who are always trying to find ways to maximize performance. post-game Cortisol levels than did an increase in status. In contrast to previous

The Effects of a Social-Evaluative Body Image Threat on Shame, Social Physique Anxiety, Body Dissatisfaction and Cortisol Responses in University Men

Men struggle with body image concerns particularly related to the desire to be muscular. In women, social-evaluative body image threats have been linked to increased shame and cortisol responses, consistent with social self-preservation theory (SSPT), but no research has investigated these responses in men. Men (n = 66) were randomly assigned to either a social-evaluative threat (SET) or non-social-evaluative threat (N-SET) condition. Participants provided saliva samples and completed body shame, body dissatisfaction and social physique anxiety measures prior to and following their condition, during which anthropometric and strength measures were assessed. Results indicated men in the SET condition had higher body shame, social physique anxiety, and body dissatisfaction and had higher levels of cortisol than men in the N-SET condition post-social-evaluative threat. These findings, consistent with SSPT, suggest that social-evaluative body image threats may lead to increased body shame and social physique anxiety, greater body dissatisfaction and higher cortisol levels.