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Background: Stress is today a common feature of patients seeking medical care and a growing public health issue in society. A method has been developed to measure biological chronic stress by Hair Cortisol Concentrations (HCC). This biomarker, for chronic stress, captures information about cumulative cortisol levels over the course of several months. Long-term stress might be one of the factors contributing to the onset of cardiovascular conditions and also affecting different risk factors. The aim of this study was to analyse the association between Hair Cortisol Concentrations and previous cardiovascular diseases and cardiovascular risk factors., Methods: The method of measuring chronic stress by Hair Cortisol Concentration was applied in a large Swedish national observational cross-sectional study. A population-based random sample of N = 4,821 Swedish middle-aged men and women was analysed for hair cortisol levels in relation to diagnosed previous cardiovascular diseases and biologically measured cardiovascular risk factors., Results: Long-term stress, measured by hair cortisol, was significantly associated with the classical cardiovascular risk factors hypertension and high cholesterol, but not smoking. Those with elevated HCC levels also had a significantly increased pre-history of myocardial infarction, type 2 diabetes, atrial fibrillation and by-pass surgery, but not regarding stroke, angina pectoris or sleep apnoea. Higher HCC was significantly associated (p < 0.001) with Body mass index and waist circumference, but only for females. HCC was also associated with the risk markers leukocytes, and high-sensitivity CRP, indicating a possible linkage between HCC and inflammation and hypothetically also the bodily immune defense. No association was found between perceived stress and HCC., Conclusions: An overall conclusion of our results is that health care should put more emphasis on patients reporting that they have been exposed to long term stress. Altogether, these analyses of Hair cortisol levels in a large middle-aged population show that chronically elevated cortisol levels represent a relevant and significant factor associated with cardiovascular diseases and classical cardiovascular risk factors., (© 2024. The Author(s).)

Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal (HPA) axis activity, which is related to emotion regulation. We compare hair cortisol concentrations (HCC), in clinically referred children with disruptive mood dysregulation disorder (DMDD) (n = 19), children with other types of psychological disorders (n = 48), and healthy subjects (n = 36). We also investigate the association between HCC and irritability, age, and sex. Our results show that children with DMDD or other types of psychological disorders have higher HCC than healthy subjects, p < .001, η p 2 = .39. No difference between children with DMDD and those with other types of psychological disorders was found, p = .91, nor an association between HCC and irritability in the clinical sample, p = .32. We found a significant negative correlation between HCC and age in those with DMDD, r = -0.54, p < .05, but not in the normative sample, r = -0.20, p = .25. No differences in HCC between girls and boys were found in the normative sample, p = .49. Children in need of psychological treatment, including those with DMDD, seem to have dysregulated HPA-axis activity over time. Excessive accumulated cortisol concentrations in hair could be an indicator of a psychological disorder in children., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ambulance personnel in emergency medical services are exposed to physical demands and stress during work, and an increased prevalence of ill health has been observed in this group. The aim was to compare hair cortisol concentration (HCC) among Swedish ambulance personnel with HCC in a population-based reference sample, to analyse differences between women and men, and differences due to work-related factors. Samples of hair 1 cm closest to the skin (5-10 mg) were collected and analysed for cortisol by radioimmunoassay. Moreover, the participants responded to a questionnaire regarding their work environment. The HCC among the ambulance personnel did not differ from the HCC in the population-based reference sample (median 19.2 vs. 22.2 pg/mg, p = 0.319), nor were there statistically significant differences between women and men. Furthermore, no associations were found between HCC and physical and psychosocial work demands, work stress, or rest and recovery from work. However, occupational balance was positively correlated with HCC (r p  = 0.240; p = 0.044). The association remained statistically significant after adjustment for sex, age, hair bleaching, and corticosteroid treatment in a linear regression model. This study adds knowledge regarding HCC among ambulance personnel, and thus contributes to the overall picture of work environment and health for this group., (© 2023. Springer Nature Limited.)

Bullying has been identified as the most common form of aggression and a major source of stress among children and adolescents. The main objective of this study was to analyze the association that school context in general and bullying in particular might have with hair cortisol concentration (HCC), examining the effect of executive function and sex on this association. The study included 659 11-year-old preadolescents from the cohorts of Gipuzkoa and Sabadell of the INMA (INfancia y Medio Ambiente-Children and Environment) project. We gathered information about school-related factors (bullying, school environment, problems with peers and academic performance) and executive function (risky decision-making). Hair samples were collected to measure cortisol concentrations and Structural Equation Modeling was used to examine associations between school-related factors, executive function and HCC. Results showed that being involved as a bully/victim was related to higher HCC and, higher HCC was associated with poorer executive function. This study may contribute to a better understanding of the consequences that chronic exposure to a stressful factors may have on preadolescents' health and developmental outcomes. Besides, our results are relevant for designing programs for prevention and intervention, which could modify individual physiological responses to stress and reduce the effects of stress on the health.

Objective: To determine if preterm birth is associated with adaptation of the hypothalamic-pituitary-adrenal (HPA) axis and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at <28 weeks or very preterm birth at 28-32 weeks gestation)., Design: This study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age., Setting: Infants born at a single Scottish hospital., Participants: 45 term-born, 42 very preterm and 16 extremely preterm infants., Outcomes: Cortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol., Results: Compared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/L, difference in means: -7.3 nmol/L, 95% CI -14.0 to -0.6) and a flattened diurnal slope (difference in geometric means: -72.9%, 95% CI -87.1 to -42.8). In contrast, the cortisol response to vaccination (difference in means -2.7 nmol/L, 95% CI -7.4 to 2.0) and diurnal slope at 4 months (difference in geometric means: -33.6%, 95% CI -62.0 to 16.0) did not differ significantly in infants born very preterm compared with infants born at term., Conclusions: Infants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity and could contribute to later metabolic and neurodevelopmental phenotypes observed in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Hypothalamic-pituitary-adrenal (HPA) axis adaptation is a potential mechanism linking early life exposures with later adverse health. This study tested the hypothesis that preterm birth is associated with adaptation of diurnal cortisol regulation across infancy., Methods: A secondary analysis was conducted of saliva cortisol measured morning, midday and evening, monthly, across infancy, as part of a birth cohort conducted in Linköping, Sweden. Diurnal cortisol regulation of infants born extremely preterm (n=24), very preterm (n=27) and at term (n=130) were compared across infancy through random coefficients regression models., Results: Compared with infants born at term, infants born extremely preterm (-17.2%, 95% CI: -30.7 to -1.2), but not very preterm (1.7%, 95% CI: -14.1 to 20.4), had a flattened diurnal slope across infancy., Conclusions: Extremely preterm birth is associated with a flattened diurnal slope in infancy. This pattern of cortisol regulation could contribute to adverse metabolic and neurodevelopmental phenotypes observed in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The pathogenesis of paediatric appendicitis is still an enigma. In recent years, it has become more evident that our inherent immunological responses affect the trajectory of the disease course. Long-term stress has an impact on our immune system; however, it is practically and ethically challenging to prospectively track blood measurements of cortisol-levels in asymptomatic children should an acute appendicitis episode develop. The aim of this case-control study was therefore to evaluate the effect of increased stress measured as historical imprints in hair (hair cortisol concentrations [HCC]), on the risk of developing appendicitis and complicated appendicitis. 51 children (aged < 15 years) with appendicitis (34 with complicated appendicitis), were compared to 86 healthy controls. HCC reflecting the activity of the HPA-axis 0-3 and 4-6 months prior to sampling was evaluated and compared between groups as well as between the two measurements of each study subject. In the univariate analysis with both cases and controls, an increase in HCC between the measurement timepoints was associated with a substantial increase in risk of appendicitis (OR 7.52 [95% CI 2.49-22.67], p = 0.001). This increased risk remained in the multivariate analysis after adjustment for age, sex and season (aOR OR 10.76 [95%CI 2.50-46.28], p  = 0.001). When comparing the cases of uncomplicated and complicated appendicitis through a multivariate analysis, adjusted for age and sex, the children with an increased HCC prior to appendicitis had a substantial and statistically significant increase in risk of complicated appendicitis (aOR 7.86 [95% CI 1.20-51.63], p = 0.03). Biological stress, measured as an increase in HCC, seems to be associated with an increased risk of paediatric appendicitis and a more complicated disease course., (© 2021. The Author(s).)

Objective: To investigate hair cortisol concentrations (HCC) monthly in pregnant women and to explore the effect of parity., Design: Prospective cohort study from gestational week (GW) 26, at childbirth and postpartum., Setting: An antenatal care clinic in southeast Sweden., Sample: 390 pregnant women., Methods: Cortisol was measured using radioimmunoassay in methanol extracts of ground hair samples., Main Outcome Measures: Hair cortisol concentrations., Results: Both primi- and multiparae exhibited an increase in HCC throughout pregnancy. Primiparae had significantly higher HCC in the latter part of the last trimester compared with multiparae (1 month P = 0.003, 2 months P = 0.038). The use of psychotropic medication in the first trimester correlated to HCC postpartum (P < 0.001). HCC in GW 14-17 was associated with HCC in GW 18-21 (primiparae and multiparae, P < 0.001), GW 22-25 (primiparae P = 0.036, multiparae P = 0.033), and 2 months postpartum (primiparae P = 0.049). HCC in GW 18-21 was associated with GW 22-25 in both primiparae (P < 0.001) and multiparae (P < 0.001) as well as 2 months prior to childbirth among primiparae (<0.037). In general, all estimates of HCC in pregnancy and postpartum showed a significant association between HCC for a specific month and the HCC in the previous month (all P < 0.001), except for the association of HCC among primiparae in GW 22-25 and 3 months prior to childbirth., Conclusions: Increased cortisol concentrations in hair were observed during pregnancy, which decreased 3 months prior to childbirth in multiparae. The results indicate a quicker suppression of the hypothalamic CRH (corticotropin-releasing hormone) production by placenta CRH in multiparous women., Tweetable Abstract: Multiparae have a quicker suppression of hypothalamic CRH production by placenta CRH during pregnancy compared to primiparae., (© 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Long term stress exposure is typical for modern societies and might trigger different diseases. This case-control study reveals that persons who had suffered an acute myocardial infarction (AMI) had elevated cortisol concentrations in the month before the acute event. Middle-aged patients admitted to cardiology clinics with acute myocardial infarction (AMI) (n = 174) were compared to 3156 controls from a population-based cohort in southeast Sweden. The median Hair Cortisol Concentrations (HCC) for those who had suffered an AMI was 53.2 pg/mg compared to 22.2 pg/mg for the control group (p < 0.001). In bivariate analysis, higher levels of HCC were strongly (OR = 5.69) and statistically significantly associated with current AMI status. The discrimination of cases with AMI from controls remained statistically significant (OR = 5.04) even after controlling for established cardiovascular risk factors in a multivariate analysis. Middle-aged persons with acute myocardial infarction had significantly elevated cortisol levels during the month before the cardiac event. This was evident for both men and women. The biomarker cortisol concentration was independently and statistically significantly related to AMI. Chronic stress seems to be a new promising risk factor for AMI.

Aim: To assess mental health outcomes of very low birthweight (VLBW, <1500 g) subjects to adulthood and to examine salivary cortisol and hair cortisol levels and their relation to birth characteristics and mental health., Methods: A Swedish regional cohort of 56 VLBW subjects and 55 full-term controls were assessed at the ages 27-28 with adult self-reported scales and the mean of 2 days diurnal salivary cortisol and hair cortisol. The cohorts had been assessed at 15 years of age with youth self-reported scales., Results: There were no differences between the groups in youth self-reported scales and adult self-reported scores. The 24 participating VLBW girls scored lower on youth self-reported scales externalising and total problem scores than the control girls. In adulthood, the 21 participating VLBW women had significantly higher morning concentrations of salivary cortisol than control women, P = .014. No significant associations were found between cortisol concentrations and adult self-reported scales internalising, externalising and total scores., Conclusion: Self-reported mental health in VLBW subjects was comparable with normal birthweight controls indicating a satisfying transition from adolescence to adulthood. VLBW females had higher morning salivary cortisol concentrations, suggesting a gender difference. We found no correlations between cortisol and mental health., (© 2019 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

The aim of this study was to analyse the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between women operated with robotic and abdominal hysterectomy in treating early-stage endometrial cancer. At a Swedish university hospital fifty women with early-stage low-risk endometrial cancer were allocated to robotic or abdominal hysterectomy in a randomiszed controlled trial. Blood samples reflecting inflammatory responses (high sensitivity CRP, white blood cells (WBC), thrombocytes, IL-6, cortisol) and tissue damage (creatine kinase (CK), high-mobility group box 1 protein (HMGB1)) were collected one week preoperatively, just before surgery, postoperatively at two, 24 and 48 hours, and one and six weeks postoperatively. High sensitivity CRP (p = 0.03), WBC (p < 0.01), IL-6 (p = 0.03) and CK (p = 0.03) were significantly lower in the robotic group, but fast transitory. Cortisol returned to baseline two hours after robotic hysterectomy but remained elevated in the abdominal group comparable to the preoperative high levels for both groups just before surgery (p < 0.0001). Thrombocytes and HMGB1 were not affected by the mode of surgery. Postoperative inflammatory response and tissue damage were lower after robotic hysterectomy compared to abdominal hysterectomy. A significant remaining cortisol elevation two hours after surgery may reflect a higher stress response in the abdominal group.

Objective: Satisfactory anabolic reactions, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis, are essential following severe traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH). Many factors may influence this activation. This study aimed to investigate whether individuals who reported chronic diseases, psychosocial afflictions, or stressful events before a severe brain injury display a different pattern regarding cortisol levels retrospectively and up to three months compared with those who did not report stressful experiences., Materials and Methods: Fifty-five patients aged 16-68 years who were admitted to the neurointensive care unit (NICU) were included. Hair cortisol measurements offer a unique opportunity to monitor cortisol levels retrospectively and after the trauma. Hair strands were collected as soon as possible after admission to the NICU and every month until three months after the injury/insult. The participants/relatives were asked about stressful events, psychosocial afflictions and recent and chronic diseases., Results: The group who reported chronic diseases and/or stressful events before the brain injury had more than twice as high median hair cortisol levels before the brain injury compared with those who did not report stress, but the difference was not statistically significant (P = .12). Those who reported stress before the brain injury had statistically significantly lower hair cortisol values after the brain injury and they remained until three months after the injury., Conclusions: Stressful events and/or chronic disease before brain injury might affect mobilization of adequate stress reactions following the trauma. However, the large variability in cortisol levels in these patients does not allow firm conclusions and more studies are needed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life., Methods: This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire., Results: A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02)., Conclusions: Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

Objective: Stress is an important component in the pathophysiology of irritable bowel syndrome (IBS). Long term Hypothalamus Pituitary Adrenal (HPA)-axis activity can be studied by measuring hair cortisol concentrations (HCC). Some previous studies have indicated a dysregulated HPA-axis in IBS patients, but cortisol levels in hair have not yet been studied. We investigated whether HCC and self-reported stress differentiate IBS patients from controls., Methods: In a cross-sectional study within 10 Swedish Primary Health Care Centers we compared patients in working age with active IBS to patients without GI complaints. The participants donated hair samples and completed questionnaires including a scale of self-reported perceived stress (PSS). 169 Rome III-fulfilling IBS patients and 316 non-IBS patients were available for final analyses., Results: IBS patients had significantly lower HCC, median=16.3pg/mg, IQR=26.9pg/mg, compared to non-IBS patients, median=22.8pg/mg, IQR=29.1pg/mg. There was also a difference in the distribution of HCC quintiles between the two groups, with 30.2% IBS patients and 14.2% of non-IBS patients in the lowest quintile of HCC. PSS was higher among IBS patients with a mean (SD) total score of 25.3 (8.0) compared to controls 21.4, (7.5). Quintiles of HCC and PSS stayed significantly but very weakly related to IBS (B=-0.332, Std error=0.146, p<0.005) in multivariable analyses., Conclusion: This study suggests a possible suppression of the HPA-axis activity in a considerable portion of IBS patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

It is challenging to measure long-term endocrine stress responses in animals. We investigated whether cortisol extracted from dog hair reflected the levels of activity and stress long-term, during weeks and months. Hair samples from in total 59 German shepherds were analysed. Samples for measuring cortisol concentrations were collected at three occasions and we complemented the data with individual scores from the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). Generalised linear mixed model (GLMM) results showed that hair cortisol varied with season and lifestyle: competition dogs had higher levels than companion, and professional working dogs, and levels were higher in January than in May and September. In addition, a positive correlation was found between the cortisol levels and the C-BARQ score for stranger-directed aggression (r = 0.31, P = 0.036). Interestingly, the factor "playing often with the dog" (r = -0.34, P = 0.019) and "reward with a treat/toy when the dog behaves correctly" (r = -0.37, P = 0.010) correlated negatively with cortisol levels, suggesting that positive human interactions reduce stress. In conclusion, hair cortisol is a promising method for revealing the activity of the HPA-axis over a longer period of time, and human interactions influence the cortisol level in dogs.

Background: Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life., Methods: 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist., Results: A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life., Conclusions: Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

Background: Early psychosocial exposures are increasingly recognized as being crucial to health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity. The objective was to investigate whether early-life adverse psychosocial circumstances influence infant cortisol levels in hair and health outcomes in children prospectively until age 10., Methods: A cohort study in the general community using a questionnaire covering 11 psychosocial items in the family during pregnancy and the cumulative incidence of diagnoses until age 10 years in 1876 children. Cortisol levels in hair were measured by using a radioimmunoassay in those with sufficient hair samples at age 1, yielding a subsample of n = 209., Results: Children with added psychosocial exposures had higher infant cortisol levels in hair (B = 0.40, P < .0001, adjusted for gender and size for gestational age) in a cumulative manner and were significantly more often affected by 12 of the 14 most common childhood diseases, with a general pattern of increasing odds ratios., Conclusions: The findings support the model of physiologic dysregulation as a plausible mechanism by which the duration and number of early detrimental psychosocial exposures determine health outcomes. The model indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance., (Copyright © 2015 by the American Academy of Pediatrics.)

Aim: To evaluate the effects of almost continuous skin-to-skin contact (SSC) on salivary cortisol, parental stress, parental depression, and breastfeeding., Study Design: This is a randomised study engaging families of late preterm infants (32-35 weeks gestation). Salivary cortisol reactivity was measured in infants during a nappy change at one month corrected age, and in infants and mothers during still-face at four month corrected age. Both parents completed the Swedish Parenthood Stress Questionnaire (SPSQ) at one month and the Edinburgh Postnatal Depression Scale (EPDS) at one and four months. Ainsworth's sensitivity scale was used to control for parental sensitivity., Subjects: Thirty-seven families from two different neonatal care units in Sweden, randomised to either almost continuous SSC or standard care (SC)., Results: Infants randomised to SSC had a lower salivary cortisol reactivity at one month (p=0.01). There was a correlation between the mothers' and the preterm infants' salivary cortisol levels at four months in the SSC group (ρ=0.65, p=0.005), but not in the SC group (ρ=0.14, p=0.63). Fathers in SSC scored lower on the SPSQ sub-scale spouse relationship problems compared to fathers in SC (p<0.05)., Conclusions: Almost continuous SSC decreases infants' cortisol reactivity in response to handling, improves the concordance between mothers' and infants' salivary cortisol levels, and decreases fathers' experiences of spouse relationship problems., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate cortisol concentrations in hair as biomarker of prolonged stress in young children and their mothers and the relation to perinatal and sociodemographic factors., Methods: Prospective cohort study of 100 All Babies In Southeast Sweden study participants with repeated measures at 1, 3, 5, and 8 years and their mothers during pregnancy. Prolonged stress levels were assessed through cortisol in hair. A questionnaire covered perinatal and sociodemographic factors during the child's first year of life., Results: Maternal hair cortisol during the second and third trimester and child hair cortisol at year 1 and 3 correlated. Child cortisol in hair levels decreased over time and correlated to each succeeding age, between years 1 and 3 (r = 0.30, P = .002), 3 and 5 (r = 0.39, P < .001), and 5 and 8 (r = 0.44, P < .001). Repeated measures gave a significant linear association over time (P < .001). There was an association between high levels of hair cortisol and birth weight (β = .224, P = .020), nonappropriate size for gestational age (β = .231, P = .017), and living in an apartment compared with a house (β = .200, P = .049). In addition, we found high levels of cortisol in hair related to other factors associated with psychosocial stress exposure., Conclusions: Correlation between hair cortisol levels in mothers and their children suggests a heritable trait or maternal calibration of the child's hypothalamic-pituitary-adrenocortical axis. Cortisol output gradually stabilizes and seems to have a stable trait. Cortisol concentration in hair has the potential to become a biomarker of prolonged stress, especially applicable as a noninvasive method when studying how stress influences children's health.

The worldwide financial crisis during recent years has raised concerns of negative public health effects. This is notably evident in southern Europe. In Greece, where the financial austerity has been especially pronounced, the prevalence of mental health problems including depression and suicide has increased, and outbreaks of infectious diseases have risen. The main objective in this study was to investigate whether different indicators of health and stress levels measured by a new biomarker based on cortisol in human hair were different amongst comparable Greek and Swedish young adults, considering that Sweden has been much less affected by the recent economic crises. In this cross-sectional comparative study, young adults from the city of Athens in Greece (n = 124) and from the city of Linkoping in Sweden (n = 112) participated. The data collection comprised answering a questionnaire with different health indicators and hair samples being analyzed for the stress hormone cortisol, a biomarker with the ability to retrospectively measure long-term cortisol exposure. The Greek young adults reported significantly higher perceived stress (p<0.0001), had experienced more serious life events (p = 0.002), had lower hope for the future (p<0.0001), and had significantly more widespread symptoms of depression (p<0.0001) and anxiety (p<0.0001) than the Swedes. But, the Greeks were found to have significantly lower cortisol levels (p<0.0001) than the Swedes, and this difference was still significant in a multivariate regression (p<0.0001), after adjustments for potential intervening variables. A variety of factors related to differences in the physical or socio-cultural environment between the two sites, might possibly explain this finding. However, a potential biological mechanism is that long-term stress exposure could lead to a lowering of the cortisol levels. This study points out a possible hypothesis that the cortisol levels of the Greek young adults might have been suppressed and their HPA-axis down-regulated after living in a stressful environment with economic and social pressure.

Stress and/or anxiety during pregnancy affect maternal and fetal well-being and can cause premature delivery and postnatal pathology in the child. Women suffering from phobias related to blood and injections are prone to high levels of stress, including anxiety and sometimes panic attacks, during pregnancy. Cortisol is amongst the mediators through which the neurohormonal expressions of maternal psychological factors may be transduced to the fetus. The aim of this study was to investigate whether pregnant women suffering from blood and injection phobia have raised cortisol levels or are characterized by unusual diurnal salivary cortisol profiles compared with healthy controls. The sample consisted of 110 pregnant women with blood and injection phobia and 110 pregnant healthy controls. Both groups provided morning and evening saliva samples in weeks 25 and 36 for the assay of cortisol. In gestational week 25, when blood was drawn for the mandatory blood testing, extra blood was taken to analyze corticotrophin-releasing factor, adrenocorticotropic hormone, and cortisol in serum. The diurnal decline in salivary cortisol as well as increased cortisol levels were observed during pregnancy. Pregnant women suffering from blood and injection phobia had a higher output of cortisol compared with women without the phobia (F = 6.25, df = 1, p = 0.014), but no marked difference in the diurnal cortisol rhythm was found between groups. Our findings indicate that untreated blood and injection phobia during pregnancy increases cortisol concentrations. Blood and injection phobia is treatable, and cognitive behavioral therapy can be used. Women with blood and injection phobia during pregnancy therefore need to be recognized and offered treatment without delay in early pregnancy.

The aims of the present study were to investigate (1) whether the salivary cortisol response could be dampened during a routine three-month immunization if the infant received sweet-tasting solution in combination with a pacifier and (2) stress experienced by parents during immunization of the infant. Ninety-eight infants were included into one of four intervention groups: 'glucose and pacifier', 'water and pacifier', 'glucose', or 'water'. Saliva was collected before and 30 min after the immunization. Infants' crying-time and parents' self-reported stress (VAS) were measured before and after immunization. Infants in the 'pacifier and glucose' group had a significantly smaller change in salivary cortisol than infants in the other groups (F(3,72)=3.1, p<0.05). In the 'glucose and pacifier' group the median salivary cortisol levels decreased 33% after the immunization. In the 'water and pacifier', 'glucose', and 'water' group median cortisol increased with 50%, 42%, and 8%, respectively. No significant differences in crying-time were observed between the intervention groups. If the infant cried before the immunization, the crying-time during the immunization was longer (p<0.01) and cortisol increased more (p<0.05). Median cortisol levels for parents decreased after the immunization (p<0.01). Median VAS increased 50% (p<0.0001) after immunization. First time parents rated higher stress on VAS before immunization (p<0.01). Parents' change in cortisol and VAS were significantly related to infants' crying time. In conclusion, the combination of oral glucose and pacifier dampen infants' salivary cortisol in response to the three-month immunization.

The aims of the present study were to investigate whether the cotton-tipped applicators (cotton buds) used to collect saliva in infants can be stored un-centrifuged prior to cortisol analysis, and to test whether there is any difference in results between wooden and plastic-shafted sticks. Saliva was collected from 10 healthy adults using 6 cotton buds, i.e. 3 with wooden sticks and 3 with plastic sticks. The samples were then centrifuged at three different time-points: immediately after collection, after 24 h and after 48 h. Using cotton buds with wooden sticks, median salivary cortisol was significantly lower after 24 h (40 %) (p<0.001) and after 48 h (49 %) (p<0.001) of storage than it was of the samples centrifuged immediately. There was no significant difference between the samples centrifuged immediately and those centrifuged after 24 h and 48 h when saliva was collected using the cotton buds with plastic sticks. It is concluded that cotton buds with wooden sticks should not be used in studies of salivary cortisol unless it is possible to centrifuge the saliva immediately. Moreover, it is inadvisable to alternate between cotton buds with wooden and plastic sticks in the same study when collecting saliva for analysis of cortisol.

Objectives: Mother-infant separation after birth is a well-known source of stress. Parents and preterm infants in neonatal intensive care are separated immediately after birth. Skin-to-skin care is 1 possible method to reduce the separation-dependent stress. The aim of the present study was to investigate how skin-to-skin care influences stress for the mother and the infant in neonatal intensive care., Methods: Seventeen mother-infant pairs were included at their first and fourth skin-to-skin care. The infants were 25 to 33 weeks' gestational age, with birth weights ranging from 495 to 2590 g. In mothers, salivary cortisol, heart rate, mood scale, and stress measured on a visual analog scale (VAS) were analyzed. In infants, salivary cortisol and heart rate were analyzed, and because pain is one facet of stress, 2 different pain scales were used., Results: In mothers, the skin-to-skin care decreased salivary cortisol (32%), heart rate (7%), and VAS (89%), whereas mood increased (6%). Before the fourth skin-to-skin care, mothers rated less stress on VAS, and salivary cortisol and heart rate improved faster. The infants' cortisol either increased or decreased. Their heart rates and pain scores decreased during skin-to-skin care., Conclusions: Our results lend additional support to the value of skin-to-skin care in neonatal intensive care. Variable stress responses in preterm infants favor the need for individualized care. The mothers' need for support seem to be more pronounced in the first skin-to-skin session as our results show a higher degree of stress as compared with later skin-to-skin care.

Newborn infants are subject to repetitive painful and stressful events during neonatal intensive care. When the baby attempts to cope with a stressful situation the hypothalamus-pituitary-adrenal axis is activated, releasing cortisol. The free cortisol response is optimally measured in saliva and saliva samples can be taken easily and without pain. However, saliva is very scarce in infants and saliva stimulants can interfere with analytical methods. Nowadays, sweet solutions are frequently administered to neonates prior to a disturbing procedure in order to reduce pain. The possible interference of sweet solutions with the measurement of salivary cortisol has not yet been documented. The aims of the present study were to further improve the detection limit of the radioimmunoassay used for cortisol analysis and to determine the degree of interference of high concentrations of glucose with the analytical method. By decreasing incubation temperature and prolonging the incubation time it was possible to improve the detection limit of the radio immunoassay (RIA) to 0.5 nmol/L at the same time as the sample volume was decreased to 10 microL saliva. Saliva was collected from full-term and preterm babies and was sufficient for analysis in 113 out of 116 (97%) samples. Glucose in the concentrations and amounts commonly used for pain relief did not interfere with the RIA method. In conclusion, it is feasible to collect microlitre volumes of saliva and analyse even very low concentrations of cortisol in newborns. It is also possible to offer the baby oral glucose prior to a painful procedure and still reliably measure salivary cortisol.

Measuring cortisol in saliva offers important advantages compared to measurement in plasma or serum. However, the sampling procedure and also the detection limit cause problems, especially in paediatric and neonatal care. We describe a simple and efficient sampling procedure, together with a modification of a radioimmunoassay, which enables analysis of low (down to 1 nmol/L) concentrations of salivary cortisol (10 times lower detection limit than in the original procedure). This setting was used in studying salivary cortisol concentrations before and after heelstick on healthy newborn infants. A significant rise (median 81%; p<0.01) in salivary cortisol as response to this invasive stressor was noted.

Cortisol is one of the primary mediators of the stress response, in the main having immunosuppressive effects. An important component of the host response in periodontal inflammation is gingival crevicular fluid (GCF), with constituents mainly derived from serum. Cortisol, like many other steroids, is present in saliva but its occurrence in GCF does not seem to be documented. Unstimulated whole saliva was collected and GCF was sampled on filter disks. The samples were analysed by a modified RIA method for serum in such a way that small volumes and low concentrations could be measured. Our findings suggest that the total concentration of cortisol in GCF might be estimated to levels below 1/10 of that in serum. However, what appears as a distinctive feature is the considerable variation of the cortisol concentrations for individual teeth. To our knowledge, this is the first time cortisol has been measured in gingival crevicular fluid, and this opens the prospects for further in vivo research.

Objective: To investigate hair cortisol concentrations (HCC) monthly in pregnant women and to explore the effect of parity. Design: Prospective cohort study from gestational week (GW) 26, at childbirth and postpartum. Setting: An antenatal care clinic in southeast Sweden. Sample: 390 pregnant women. Methods: Cortisol was measured using radioimmunoassay in methanol extracts of ground hair samples. Main outcome measures: Hair cortisol concentrations. Results: Both primi‐ and multiparae exhibited an increase in HCC throughout pregnancy. Primiparae had significantly higher HCC in the latter part of the last trimester compared with multiparae (1 month P = 0.003, 2 months P = 0.038). The use of psychotropic medication in the first trimester correlated to HCC postpartum (P < 0.001). HCC in GW 14–17 was associated with HCC in GW 18–21 (primiparae and multiparae, P < 0.001), GW 22–25 (primiparae P = 0.036, multiparae P = 0.033), and 2 months postpartum (primiparae P = 0.049). HCC in GW 18–21 was associated with GW 22–25 in both primiparae (P < 0.001) and multiparae (P < 0.001) as well as 2 months prior to childbirth among primiparae (<0.037). In general, all estimates of HCC in pregnancy and postpartum showed a significant association between HCC for a specific month and the HCC in the previous month (all P < 0.001), except for the association of HCC among primiparae in GW 22–25 and 3 months prior to childbirth. Conclusions: Increased cortisol concentrations in hair were observed during pregnancy, which decreased 3 months prior to childbirth in multiparae. The results indicate a quicker suppression of the hypothalamic CRH (corticotropin‐releasing hormone) production by placenta CRH in multiparous women. Multiparae have a quicker suppression of hypothalamic CRH production by placenta CRH during pregnancy compared to primiparae. Multiparae have a quicker suppression of hypothalamic CRH production by placenta CRH during pregnancy compared with primiparae. [ABSTRACT FROM AUTHOR]

Various mediators of pruritus have been suggested that might be responsible for the mechanism of pruritus in psoriasis. To study the expression levels of members of the tachykinin family, substance P and neurokinin (NK) A and their receptors, NK-1 and NK-2, in psoriasis and to correlate their expression with the intensity of pruritus. A possible correlation with chronic stress and depression was also evaluated. Biopsies were obtained from 28 patients with chronic plaque psoriasis; the majority had pruritus. The samples were taken from lesional and nonlesional areas on the back and also from 10 healthy controls, for immunohistochemistry staining, and from lesional skin for radioimmunoassay. Prior to biopsy, the clinical severity of the psoriasis of each patient was assessed by the Psoriasis Area and Severity Index (PASI) and the intensity of pruritus was measured by using a visual analogue scale (VAS). Levels of depression and stress were measured using Beck's Depression Inventory (BDI) and the salivary cortisol test, respectively. Substance P-, NKA- and NK-2 receptor-immunoreactive nerves, and non-neuronal inflammatory cells positive for substance P and NKA and their respective receptors, NK-1 and NK-2, were numerous in psoriasis compared with healthy controls. The numbers of substance P-positive nerves and NK-2 receptor-positive cells in lesional skin were significantly correlated to pruritus intensity. The cortisol ratio was inversely correlated with the number of NK-1 receptor-immunoreactive inflammatory cells in lesional and nonlesional psoriasis skin. There was also a positive correlation between the BDI score and the number of substance P-positive cells in nonlesional skin and with NK-1 receptor-positive cells in lesional and nonlesional skin. Tachykinins may play a role in psoriasis per se, in addition to pruritus in this disease. Targeting the combined NK-1 and NK-2 receptors might be a possible treatment. [ABSTRACT FROM AUTHOR]