Prenatal maternal emotional complaints are associated with cortisol responses in toddler and preschool aged girls

Associations between prenatal maternal emotional complaints and child behavioral and cognitive problems have been reported, with different relations for boys and girls. Fetal programming hypotheses underline these associations and state that the early development of the HPA‐axis of the children may have been affected. In the present study, differences in cortisol responses of prenatally exposed and nonexposed children are examined for both sexes separately. Cortisol response patterns of a group preschool aged children that were prenatally exposed to high levels of maternal emotional complaints (N = 51) were compared to a nonexposed group (N = 52). Child saliva was collected at the start of a home visit (T1), 22 min after a mother–child interaction episode (T2), and 22 min after a potentially frustrating task (T3). Repeated measures analyses showed that prenatally exposed girls showed higher cortisol levels across the three episodes compared to nonexposed girls. No differences were found in boys. Maternal prenatal emotional complaints might be related to child HPA‐axis functioning differently for boys and girls. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 553–563, 2009.     

Prenatal cortisol exposure predicts infant cortisol response to acute stress

Experimental animal findings suggest that early stress and glucocorticoid exposure may program the function of the hypothalamic–pituitary–adrenal (HPA) axis in the offspring. The extension of these findings to human development is not yet clear. A prospective longitudinal study was conducted on 125 mothers and their normally developing children. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infant behavior and cortisol response to a separation–reunion stress was assessed at 17 months. Amniotic fluid cortisol predicted infant cortisol response to separation–reunion stress: infants who were exposed to higher levels of cortisol in utero showed higher pre‐stress cortisol values and blunted response to stress exposure. The association was independent of prenatal, obstetric, and socioeconomic factors and child–parent attachment. The findings provide some of the strongest data in humans that HPA axis functioning in the child may be predicted from prenatal cortisol exposure. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 145–155, 2013     

Dampening of the cortisol response to handling at 3 months in human infants and its relation to sleep,circadian cortisol activity,and behavioral distress

The decrease in responsiveness of the hypothalamic–pituitary–adrenocortical (HPA) system is marked over the first months of life. Seventy-eight healthy infants (44 girls), 7 to 15 weeks old, were given a laboratory mock physical examination. Salivary cortisol samples were collected pre- and postexamination and at home. Behavioral state during the examination and home sleep/wake activity were measured. Subjects younger than 11 weeks showed an increase in pre- to postexamination cortisol, while older subjects did not. Further, there was no decrease in behavioral distress to the examination with age. Infants who showed an early-morning peak (EMP) in home cortisol levels were significantly older and were likely to be those who slept through the night. However, the presence of an EMP was not associated with a lack of cortisol response to the examination. The decrease in cortisol responsiveness witnessed around the age of 3 months is presumably due to other processes associated with age, and not with the expression of the day–night rhythm in basal cortisol. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 33: 327–337, 1998     

The association between prenatal exposure to cigarettes and cortisol reactivity and regulation in 7-month-old infants

We examined the association between prenatal exposure to cigarettes and adrenocortical responses to stress in 7-month-old infants. Cortisol levels were assessed twice prior to and twice following affect-eliciting procedures in 111 (59 exposed and 52 nonexposed) infants. Cortisol reactivity was defined as the difference between the peak poststressor cortisol level and the pretask cortisol level. Higher values indicated higher cortisol reactivity. Exposed infants had higher peak cortisol reactivity than nonexposed infants. There were no differences in pretask cortisol levels. Maternal hostility mediated the association between cigarette exposure and peak cortisol reactivity. Furthermore, infant gender moderated this association such that exposed boys had significantly higher peak cortisol reactivity than nonexposed infants or exposed girls. These findings provide additional evidence that prenatal cigarette exposure is associated with dysregulation during infancy and that early adverse, nonsocial experiences may have relatively long-lasting effects on cortisol reactivity in infants.     

Timing of fetal exposure to stress hormones: effects on newborn physical and neuromuscular maturation

The purpose of the study was to determine the specific periods during pregnancy in which human fetal exposure to stress hormones affects newborn physical and neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and 31 weeks' gestation. Levels of placental corticotropin-releasing hormone (CRH) and maternal cortisol were determined from plasma. Newborns were evaluated with the New Ballard Maturation Score. Results indicated that increases in maternal cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were significantly associated with decreases in infant maturation among males (even after controlling for length of gestation). Results also suggested that increases in maternal cortisol at 31 weeks were associated with increases in infant maturation among females, although these results were not significant after controlling for length of gestation. Findings suggest that stress hormones have effects on human fetal neurodevelopment that are independent of birth outcome.     

Subjective insomnia symptoms and sleep duration are not related to hypothalamic–pituitary–adrenal axis activity in older adults

Insomnia symptoms are highly prevalent in depressed older adults. This study investigates the association between hypothalamic–pituitary–adrenal (HPA) axis activity and symptoms of insomnia, respectively, sleep duration among 294 depressed and 123 non‐depressed older adults of the Netherlands Study of Depression in Older people (NESDO) study. Insomnia symptoms were defined as clinically relevant when having a score ≥ 10 points on the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Sleep duration was categorized in short (≤ 6 h per night), normal (7–8 h per night) and long (≥ 9 h per night) duration. Salivary cortisol levels were used to assess the following cortisol parameters for HPA axis activity: area under the curve with respect to the increase (AUCi) and to the ground (AUCg), diurnal slope, evening cortisol level and dexamethasone suppression ratio. Clinically relevant insomnia symptoms were present in 46% of the participants. Thirty‐two per cent of the participants were short sleepers, whereas 16% were long sleepers. However, univariate analyses showed no differences in any of the HPA axis parameters between people with and without insomnia symptoms or between the three groups with different sleep duration. In addition, no significant interaction was found between a diagnosis of depression or the severity of depressive symptoms and any of the cortisol parameters in relation to insomnia symptoms or sleep duration.     

Flow cytometric determination of glucocorticoid receptor (GCR) expression in lymphocyte subpopulations: lower quantity of GCR in patients with post-traumatic stress disorder (PTSD)

Assessment of the intracellular glucocorticoid receptor (GCR) level may be useful in monitoring functional disturbances of the hypothalamic-pituitary-adrenocortical axis or effects of prolonged steroid therapy. Cytosolic ligand binding assays have recently been supplemented by flow cytometric determination of receptor expression in individual cells. A method based on multiparametric analysis of whole blood by simultaneous labelling of intracellular GCRs and surface markers of lymphocyte subsets is described. We examined 25 healthy male volunteers and 35 age- and sex-matched post-traumatic stress disorder (PTSD) patients within 8 years from traumatic event. PTSD patients had a lower relative quantity of GCR in all lymphocyte populations tested as compared with healthy volunteers. NK cells of both groups showed higher expression of GCR than other lymphocyte subsets. In PTSD patients, the expression of GCR in B lymphocytes was also higher than in T cell. Although serum cortisol level was lower in PTSD patients, there was no correlation between cortisol level and GCR expression. Multiparameter flow cytometric determination of GCR expression in lymphocyte subpopulations may provide a useful tool for monitoring immunoregulatory action of glucocorticoids.     

Salivary alpha-amylase response to acute psychosocial stress: the impact of age

The impact of stress on health varies across the different stages of human life. Aging is associated with psychobiological changes that could limit our ability to cope with stressors. Therefore, it is crucial to clarify the physiological mechanisms that underlie the stress response and the changes that occur in them as we age. Our aim was to investigate age differences in the salivary alpha amylase (sAA) response to stress, and its relationship with other typical stress biomarkers such as cortisol and heart rate (HR). Sixty-two participants divided into two age groups (younger group: N = 31, age range: 18-35 years; older group: N = 31, age range: 54-71 years) were exposed to the Trier Social Stress Test and a control condition in a crossover design. No age differences were found in the sAA or HR responses to stress. However, the sAA global output was higher in older than younger adults. Additionally, in the stress condition, the total amount of cortisol released was positively related to the total sAA released, while the HR increase was positively related to the sAA increase. Our results do not support the existence of an attenuated autonomic nervous system response to stress in older adults, but rather a heightened sympathetic tone. Furthermore, we found further evidence of the coordination between the hypothalamus-pituitary-adrenal system and the autonomic nervous system in their response to acute psychosocial stress.     

Medial prefrontal cortex activity can disrupt the expression of stress response habituation

Recent findings suggest that the expression of hypothalamic–pituitary–adrenal (HPA) axis stress response adaptation in rats depends on top–down neural control. We therefore examined whether the medial prefrontal cortex (mPFC) modulates expression of stress response habituation. We transiently suppressed (muscimol microinfusion) or stimulated (picrotoxin microinfusion) mPFC neural activity in rats and studied the consequence on the first time response to psychological stress (restraint) or separately on the development and expression of habituation to repeated restraint. We monitored both the hormonal (corticosterone) and neural (forebrain c-fos mRNA) response to stress. Inactivation of the mPFC had no effect on the HPA-axis response to first time restraint, however increased mPFC activity attenuated stress-induced HPA-axis activity. In a three day repeated restraint stress regimen, inactivation of the mPFC on days 1 and 2, but not day 3, prevented the expression of HPA-axis hormone response habituation. In these same rats, the mPFC activity on day 3 interfered with the expression of c-fos mRNA habituation selectively within the mPFC, lateral septum and hypothalamic paraventricular nucleus. In contrast, inactivation of the mPFC only on day 3, or on all 3 days did not interfere with the expression of habituation. We conclude that the mPFC can permit or disrupt expression of HPA-axis stress response habituation, and this control depends on alteration of neural activity within select brain regions. A possible implication of these findings is that the dysregulation of PFC activity associated with depression and post-traumatic stress disorder may contribute to impaired expression of stress-response adaptation and consequently exacerbation of those disorders.     

Prenatal immobilization stress and postnatal maternal separation cause differential neuroendocrine responses to fasting stress in adult male rats

Prenatal immobilization stress (PNS) and postnatal maternal separation (MS180) are two widely used rodent models of early-life stress (ELS) that affect the hypothalamus–pituitary–adrenal (HPA) axis, cause behavioral alterations, and affect glucose tolerance in adults. We compared anxiety-like behavior, coping strategies, and HPA axis activity in PNS and MS180 adult (4-month-old) male rats and assessed their glucose tolerance and HPA axis response after mild fasting stress. Both PNS and MS180 induced a passive coping strategy in the forced swimming test, without affecting anxiety-like behavior in the elevated plus-maze. Moreover, both PNS and MS180 increased the hypothalamic corticotropin-releasing hormone expression; however, only MS180 increased the circulating corticosterone levels. Both early life stressors increased fasting glucose levels and this effect was significantly higher in PNS rats. MS180 rats showed impaired glucose tolerance 120 min after intravenous glucose administration, whereas PNS rats displayed an efficient homeostatic response. Moreover, MS180 rats showed higher circulating corticosteroid levels in response to fasting stress (overnight fasting, 12 hr), which were restored after glucose administration. In conclusion, early exposure to postnatal MS180, unlike PNS, increases the HPA axis response to moderate fasting stress, indicating a differential perception of fasting as a stressor in these two ELS models.     

Interoceptive accuracy is related to long‐term stress via self‐regulation

Interoception describes the ability to perceive internal bodily signals. Previous research found a relationship between interoceptive accuracy (IAcc) and cardiovascular outcomes during or after acute stress. So far, the association between IAcc and long‐term stress has not been investigated, although this would be important to identify a starting point to prevent long‐term stress. To address this idea in the current study, we examined the relationship between IAcc and long‐term stress, which was assessed with different questionnaires and biological markers, including cortisol and dehydroepiandrosterone (DHEA). Furthermore, we investigated self‐regulation as a mechanism linking IAcc to long‐term stress. The sample consisted of 98 participants. To measure IAcc, participants completed the heartbeat perception task. Perceived long‐term stress and self‐regulation were assessed via an online questionnaire. Moreover, hair samples were taken from 65 participants to determine long‐term stress with cortisol and DHEA as well as the ratio of both. Results showed that IAcc was positively related to DHEA and weakly negatively related to the other indicators of long‐term stress, except for the nonsignificant relationships to the indicators cortisol and stress experiences due to negative events. Furthermore, these relationships were mediated by participants' enhanced self‐regulation. Thus, our results suggest that enhanced self‐regulation could be a mechanism explaining why IAcc is associated with long‐term stress.     

Mechanisms of the primary response of the adrenal cortex to pain stress in dogs

A sharp decrease in the glucocorticoid content accompanied by an increase in the free cholesterol and a decrease in the content of esterified cholesterol were observed in the adrenal cortex of dogs 10–15 sec after nociceptive stimulation. The blood concentrations of the hormones were increased, mainly due to the proteinbound hydrocortisone fraction. The next phase of the response (30–60 sec after stimulation) was marked by activation of synthetic processes, leading to considerable accumulation of hormones in the gland. The blood glucocorticoid level was doubled, the original ratio of hydrocortisone to corticosterone was restored, and the transcortin depot was replenished. The role of the adrenal and transcortin deports of glucocorticoids in the feedback mechanism during stress is discussed.Department of Pathological Physiology, Rostov Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. K. Kulagin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 18–20, July, 1979.     

Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full-term children at 18 months corrected age

Cortisol levels were compared in children born preterm at extremely low gestational age (ELGA; 24-28 weeks), very low gestational age (VGLA; 29-32 weeks), and full-term in response to cognitive assessment at 18 months corrected age (CA). Further, we investigated the relationship between maternal interactive behaviors and child internalizing behaviors (rated by the mother) in relation to child cortisol levels. EGLA children had higher "pretest" cortisol levels and a different pattern of cortisol response to cognitive assessment compared to VGLA and full-terms. Higher cortisol levels in ELGA, but not full-term, children were associated with less optimal mother interactive behavior. Moreover, the pattern of cortisol change was related to internalizing behaviors among ELGA, and to a lesser degree VLGA children. In conclusion, our findings suggest altered programming of the hypothalamic-pituitary-adrenal (HPA) axis in preterm children, as well as their greater sensitivity to environmental context such as maternal interactive behavior.