Disturbances in early parenting of depressed mothers and cortisol secretion in offspring: A preliminary study

Background: Disturbances in cortisol secretion are associated with risk for psychiatric disorder, including depression. Animal research indicates that early care experiences influence hypothalamic-pituitary-adrenal (HPA) axis functioning in offspring. Similar effects are suggested in human development, but evidence of longitudinal associations between observed early parenting and offspring cortisol secretion is extremely limited. We studied associations between parenting disturbances occurring in the context of maternal postnatal depression (PND), and elevations in morning cortisol secretion in the adolescent offspring of PND mothers. Methods: We observed maternal parenting behaviour on four occasions through the first year and at five-year follow up in postnatally depressed (n = 29) and well (n = 20) mothers. Observations were coded for maternal sensitivity and withdrawal. Basal offspring salivary cortisol secretion was measured at 13-years, using collections over 10-days. Results: Postnatal, but not five-year, maternal withdrawal predicted elevated mean and maximum morning cortisol secretion in 13-year-old offspring. There were no significant associations between maternal sensitivity and offspring cortisol secretion. Limitations: The sample size was relatively small, and effects tended to be reduced to trend level when covariates were considered. The correlational nature of the study (albeit longitudinal) limits conclusions regarding causality. Conclusions: Individual differences in early maternal parenting behaviour may influence offspring cortisol secretion, and thereby risk for depression. Parenting interventions that facilitate active maternal engagement with the infant may be indicated for high risk populations.

Cortisol levels in response to starting school in children at increased risk for social phobia

Background: Research on depression has identified hyperactivity of the HPA axis as a potential contributory factor to the intergenerational transmission of affective symptoms. However, this has not yet been examined in the context of social phobia. The current study compared HPA axis activity in response to a universal social stressor (starting school) in children of 2 groups of women: one with social phobia and one with no history of anxiety (comparison group). To determine specificity of effects of maternal social phobia, a third group of children were also examined whose mothers had generalised anxiety disorder (GAD). Method: Children provided salivary cortisol samples in the morning, afternoon and at bedtime across 3 time-blocks surrounding the school start: a month before starting school (baseline), the first week at school (stress response), and the end of the first school term (stress recovery). Child behavioural inhibition at 14 months was also assessed to explore the influence of early temperament on later stress responses. Results: All children displayed an elevation in morning and afternoon cortisol from baseline during the first week at school, which remained elevated until the end of the first term. Children in the social phobia group, however, also displayed an equivalent elevation in bedtime cortisol, which was not observed for comparison children or for children of mothers with GAD. Children in the social phobia group who were classified as 'inhibited' at 14 months displayed significantly higher afternoon cortisol levels overall. Summary: A persistent stress response to school in the morning and afternoon is typical for all children, but children of mothers with social phobia also display atypical elevations in evening cortisol levels when at school - signalling long-term disruption of the circadian rhythm in HPA axis activity. This is the first study to report HPA axis disruption in children at risk of developing social phobia, and future research should aim to determine whether this represents a pathway for symptom development, taking early temperament into account.

Sustained striatal activity predicts eudaimonic well-being and cortisol output

Eudaimonic well-being—a sense of purpose, meaning, and engagement with life—is protective against psychopathology and predicts physical health, including lower levels of the stress hormone cortisol. Although it has been suggested that the ability to engage the neural circuitry of reward may promote well-being and mediate the relationship between well-being and health, this hypothesis has remained untested. To test this hypothesis, we had participants view positive, neutral, and negative images while fMRI data were collected. Individuals with sustained activity in the striatum and dorsolateral prefrontal cortex to positive stimuli over the course of the scan session reported greater well-being and had lower cortisol output. This suggests that sustained engagement of reward circuitry in response to positive events underlies well-being and adaptive regulation of the hypothalamic-pituitary-adrenal axis.

The impact of maternal cortisol concentrations on child arterial elasticity

Epidemiological studies suggest that glucocorticoid excess in the fetus may contribute to the pathophysiology of cardiovascular diseases in adulthood. However, the impact of maternal glucocorticoid on the cardiovascular system of the offspring has not been much explored in studies involving humans, especially in childhood. The objective of this study was to assess the influence of maternal cortisol concentrations on child arterial elasticity. One hundred and thirty pregnant women followed from 1997 to 2000, and respective children 5-7 years of age followed from 2004 to 2006 were included in the study. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of nine samples of saliva. Arterial elasticity was assessed by the large artery elasticity index (LAEI; the capacitive elasticity of large arteries) by recording radial artery pulse wave, utilizing the equipment HDI/PulseWave CR-2000 Cardiovascular Profiling System (R). The nutritional status of the children was determined by the body mass index (BMI). Insulin concentration was assessed by chemiluminescence, and insulin resistance by the homeostasis model assessment. Blood glucose, total cholesterol and fractions (LDL-c and HDL-c) and triglyceride concentrations were determined by automated enzymatic methods. The association between maternal cortisol and child arterial elasticity was assessed by multivariate linear regression analysis. There was a statistically significant association between maternal cortisol and LAEI (P=0.02), controlling for birth weight, age, BMI and HDL-c of the children. This study suggests that exposure to higher glucocorticoid concentrations in the prenatal period is associated to lower arterial elasticity in childhood, an earlier cardiovascular risk marker.

Reactivity of Nellore steers in two feedlot housing systems and its relationship with plasmatic cortisol

To evaluate reactivity to assess the temperament of Nellore steers in two feedlot housing systems (group pen or individual pen) and its relationship with plasmatic cortisol, 36 experimental units were observed five times at 28-day intervals of weight management during a 112-day feedlot confinement. A reactivity score scale ranging from 1 to 5 was applied when an animal was in the chute system. To the calmest animal, a reactivity score of 1 was ascribed and to the most agitated, 5. Blood samples were collected for cortisol analysis. No differences were found in reactivity and feedlot system. There was a relationship noted between reactivity and feedlot time in both housing systems (P < 0.01). There was a relation between reactivity and cortisol levels for group animals (P = 0.0616) and for individual ones (P < 0.01). Cortisol levels varied among housing systems (P < 0.01). Feedlot time influenced the cortisol levels (P < 0.09 individual; P < 0.01 group) and when variable time was included, these levels changed, decreasing in the group pen and increasing in individual pens. The continuous handling reduces reactivity and plasmatic cortisol, and group pen system seems to be less stressfully than individual pens. (C) 2010 Elsevier B.V. All rights reserved.

Stress, cortisol and reproduction in female pigs

Two key hypotheses emerge in the literature regarding the impact of stress on reproduction in females of any species. First, prolonged stress impairs reproduction in females. Secondly, acute stress impairs reproduction, if it occurs at a critical time during the precisely timed series of endocrine events that induce oestrus and ovulation. We reviewed studies conducted in female pigs to find support or opposition for these hypotheses in female pigs. We also considered the role of cortisol. We found confirmation that prolonged stress or the prolonged elevation of cortisol can impair reproductive processes in female pigs, but also found that there appear to be some female pigs in which reproduction is resistant to such treatments. Reproduction in female pigs appears to be resistant to acute or repeated acute stress or elevation of cortisol, even if these occur during the series of precisely timed endocrine events that induce oestrus and ovulation. Thus, we propose modified versions of the above hypotheses that are specific to female pigs. Furthermore, while cortisol may mediate the effects of prolonged stress on reproduction in female pigs, there is evidence that, in female pigs, ACTH may require the presence of the adrenal glands to impair reproduction rather than having direct effects.

A sex difference in the cortisol response to tail docking and ACTH develops between 1 and 8 weeks of age in lambs

It is important to understand factors that may influence responses to stress, as these factors may also influence vulnerability to pathologies that can develop when stress responses are excessive or prolonged. It is clear that, in adults, the sex of an individual can influence the cortisol response to stress in a stressor specific manner. Nevertheless, the stage of development at which these sex differences emerge is unknown. We tested the hypothesis that there are sex differences in the cortisol response to tail docking and ACTH in lambs of 1 and 8 weeks of age. We also established cortisol responses in males when tail docking was imposed alone and in combination with castration at these ages. In experiment 1, 1 and 8 week old male and female lambs were subjected to sham handling, tail docking or, in males, a combination of tail docking and castration. In experiment 2, we administered ACTH (1.0 IU/kg) to male and female lambs at 1 and 8 weeks of age. There were significant cortisol responses to all treatments at both ages. Sex differences in the cortisol responses to tail docking and ACTH developed between 1 and 8 weeks of age, with females having greater responses than males. The data suggest that the mechanism for the sex difference in response to tail docking may involve the adrenal glands. At both ages, in males, the cortisol response to the combined treatment of tail docking and castration was significantly greater than that for tail docking alone.

Sex difference in the suppressive effect of cortisol on pulsatile secretion of luteinizing hormone in sheep

We tested the hypothesis that there are sex differences in the inhibitory effect of cortisol on pulsatile LH secretion and pituitary responsiveness to GnRH in gonadectomized sheep. In experiment 1, pulsatile LH secretion was examined in gonadectomized ewes and rams infused with either saline, a low (250 µg/kg·h) or a high (500 µg/kg·h) dose of cortisol for 30 h. In experiment 2, direct pituitary actions of cortisol were assessed by monitoring LH pulse amplitude in response to exogenous GnRH in hypothalamo-pituitary disconnected ewes and rams infused with the low dose of cortisol. In experiment 1, the mean (±SEM) plasma LH concentration was (P < 0.05) reduced significantly during cortisol infusion in both sexes, but the effect was greater in rams. In ewes, LH pulse amplitude and frequency were reduced (P < 0.05) at the high, but not the low, cortisol dose, whereas total LH output (LH pulse amplitude multiplied by frequency) was reduced (P < 0.05) at both doses. In rams, LH pulse frequency and amplitude and total LH output were (P < 0.05) reduced significantly at both cortisol doses. In experiment 2, plasma LH concentration and pulse amplitude in response to exogenous GnRH were not affected by infusion of cortisol in either sex. We conclude that gonadectomized rams are more sensitive than gonadectomized ewes to the effects of cortisol to inhibit LH secretion and that sex differences exist in the specific actions of cortisol on LH pulses. The results of experiment 2 suggest that intact hypothalamic input to the pituitary is necessary for cortisol to inhibit pituitary responsiveness to GnRH.

Cortisol disrupts the ability of estradiol-17β to induce the LH surge in ovariectomized ewes

Stress disrupts the preovulatory luteinizing hormone (LH) surge in females, but the mechanisms are unknown. We tested the hypothesis that cortisol compromises the ability of estrogen to induce a preovulatory-like LH surge in ovariectomized ewes in both the breeding and nonbreeding season. Luteinizing hormone surges were induced in ovariectomized ewes by treatment with progesterone followed by a surge-inducing estradiol-17β (E2) stimulus using a crossover design. The experiment was replicated in the breeding and nonbreeding seasons. Cortisol reduced the incidence of LH surges irrespective of season. Cortisol increased the latency from E2 stimulus to the onset of the surge in the breeding season only and suppressed the LH surge amplitude during both seasons (P < 0.01). We conclude that cortisol can interfere with the LH surge in several ways: delay, blunt, and in extreme cases prevent the E2-induced LH surge. Furthermore, the effect of cortisol to delay the E2-induced LH surge is more pronounced in the breeding season. These results show that cortisol disrupts the positive feedback effect of E2 to trigger an LH surge and suggest the involvement of multiple mechanisms.

Cortisol interferes with the estradiol-induced surge of lutenizing hormone in the ewe

Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was ∼1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

Estradiol enables cortisol to act directly upon the pituitary to suppress pituitary responsiveness to GnRH in sheep

We have shown that cortisol infusion reduced the luteinizing hormone (LH) response to fixed hourly GnRH injections in ovariectomized ewes treated with estradiol during the non-breeding season (pituitary-clamp model). In contrast, cortisol did not affect the response to 2 hourly invariant GnRH injections in hypothalamo-pituitary disconnected ovariectomized ewes during the breeding season. To understand the differing results in these animal models and to determine if cortisol can act directly at the pituitary to suppress responsiveness to GnRH, we investigated the importance of the frequency of GnRH stimulus, the presence of estradiol and stage of the circannual breeding season. In experiment 1, during the non-breeding season, ovariectomized ewes were treated with estradiol, and pulsatile LH secretion was restored with i.v. GnRH injections either hourly or 2 hourly in the presence or absence of exogenous cortisol. Experiments 2 and 3 were conducted in hypothalamo-pituitary disconnected ovariectomized ewes in which GnRH was injected i.v. every 2 h. Experiment 2 was conducted during the non-breeding season and saline or cortisol was infused for 30 h in a cross-over design. Experiment 3 was conducted during the non-breeding and breeding seasons and saline or cortisol was infused for 30 h in the absence and presence of estradiol using a cross-over design. Samples were taken from all animals to measure plasma LH. LH pulse amplitude was reduced by cortisol in the pituitary clamp model with no difference between the hourly and 2-hourly GnRH pulse mode. In the absence of estradiol, there was no effect of cortisol on LH pulse amplitude in GnRH-replaced ovariectomized hypothalamo-pituitary disconnected ewes in either season. The LH pulse amplitude was reduced in both seasons in experiment 3 when cortisol was infused during estradiol treatment. We conclude that the ability of cortisol to reduce LH secretion does not depend upon the frequency of GnRH stimulus and that estradiol enables cortisol to act directly on the pituitary of ovariectomized hypothalamo-pituitary disconnected ewes to suppress the responsiveness to GnRH; this effect occurs in the breeding and non-breeding seasons.

Sex difference in the effect of cortisol on the LH response of the pituitary to exogenous GnRH in hypothalamo-pituitary disconnected gonadectomised sheep

We have used the hypothalamo-pituitary disconnected (HPD) sheep model to investigate direct pituitary actions of cortisol to suppress LH secretion in response to exogenous GnRH. We previously observed that, during the non-breeding season, treatment with cortisol did not suppress the LH response to GnRH in HPD gonadectomised rams or ewes.1 In the present experiment, we tested the effect of cortisol on the LH response to exogenous GnRH in gonadectomised HPD sheep during the breeding season. Using a cross-over design, HPD gonadectomised Romney Marsh rams (n = 6) and ewes (n = 5) received a saline or cortisol (250 μg/kg/h) infusion for 30 h on each of two days, one week apart. All animals were treated with 125 ng i.v. injections of GnRH every 2 h during a 6 h control period preceding the infusion and during the infusion. Jugular blood samples were taken during the control period and the first 6 h and last 6 h of the infusion (over 3 LH pulses). Mean plasma concentrations of LH and LH pulse amplitudes, driven by programmed GnRH injections, were similar in gonadectomised rams and ewes and there were no significant effects of saline infusion between the control periods or the saline infusion in either sex. The amplitude of LH pulses was significantly (P < 0.05) reduced in rams during the first 6 h of the cortisol infusion compared to the control period, but there were no effects of the cortisol infusion in ewes. These data show that, in the absence of sex steroids, there is a sex difference in the mechanism by which cortisol acts at the pituitary to reduce LH secretion in response to exogenous GnRH in HPD gonadectomized sheep during the breeding season. We conclude that the effect of cortisol to reduce secretion of LH involves an action on the pituitary, at least in gonadectomised rams.

Susceptibility of reproduction in female pigs to impairment by stress or elevation of cortisol

It is generally agreed that stress can impair reproduction. Furthermore, it is often thought that cortisol, which is secreted during stress as a result of activation of the hypothalamo-pituitary adrenal axis, is associated with this stress-induced impairment of reproduction. It has been hypothesized that reproduction in females is particularly susceptible to disruption by acute stress during the series of endocrine events that induce estrus and ovulation. Nevertheless, we found no support for this conjecture when we subjected female pigs to repeated acute stress or repeated acute elevation of cortisol during the period leading up to estrus and ovulation. Conversely, studies have demonstrated that prolonged stress and sustained elevation of cortisol can disrupt reproductive processes in female pigs. Nevertheless, in each study that demonstrated this effect, there were some animals subjected to the prolonged stressor or the sustained elevation of cortisol in which the reproductive parameters that were measured were not affected by the treatment. We propose that reproduction in female pigs is resistant to the effects of acute or repeated acute stress or acute or repeated acute elevation of cortisol even if these occur during the series of endocrine events that induce estrus and ovulation. Furthermore, while reproductive processes in some individuals are compromised, reproduction in a proportion of female pigs appears to be resistant to the effects of prolonged stress or sustained elevation of cortisol.