Hypothalamic-pituitary-adrenocortical Research Articles

RELATIONSHIP BETWEEN THE HYPOTHALMIC-PITUITARY-ADRENOCORTICAL AXIS ACTIVITY AND THE CHARACTERISTICS OF ALDOSTERONE-PRODUCING ADENOMAS

Objective: Aldosterone production can be regulated by adrenocorticotrophic hormone (ACTH) which normally controls cortisol secretion. Some cases of aldosterone-producing adenoma (APA) display features which may suggest increased sensitivity to the stimulatory effects of ACTH. The objective of this study is to investigate if there is any relationship between the hypothalamic-pituitary-adrenocortical (HPA) axis activity and the characteristics of APAs. Design and method: This is a retrospective review of the HPA axis activity of 41 histologically-confirmed APA cases which were characterised with regards to clinical, biochemical and somatic mutation status. HPA axis activity was assessed from morning plasma cortisol, ACTH and 1 mg overnight dexamethasone (DEX) suppression test. Correlation was analysed by Pearson's correlation coefficient, and the HPA axis activity between APAs with KCNJ5 mutation and those without was compared using Mann Whitney U-test. Results: Twelve out of 41 patients (29.3%) were women, median age was 49 years and 85.4% were overweight/obese. All except 2 had somatic mutations within APA. Fourteen (34.1%) were KCNJ5 mutation. Only one patient (APA not KCNJ5 mutated) had post-DEX cortisol > 50 nmol/L. Upright morning plasma aldosterone concentration (PAC) correlated with tumour size (r = 0.347, P = 0.026), plasma cortisol (r = 0.425, P = 0.006) and plasma ACTH (r = 0.446; P = 0.056). Plasma ACTH and cortisol were positively correlated (r = 0.511, P = 0.025). Higher PAC, cortisol and ACTH concentrations were in turn associated with the need for higher defined-daily-dose (DDD) of anti-hypertensive medications (r = 0.466, P = 0.002 for PAC; r = 0.315, P = 0.045 for cortisol; r = 0.449, P = 0.054 for ACTH). Higher PAC was also predictive of higher BMI (r = 0.348, P = 0.026). Plasma cortisol, ACTH, post-DEX cortisol, BMI and DDD of anti-hypertensives were not significantly different between those with KCNJ5 mutation compared to those without. Conclusions: HPA axis activity correlated with clinico-biochemical characteristics in patients with APAs, but the prevalence of autonomous hypercortisolism was low. The findings suggest a potential role of ACTH in the pathophysiology of APAs. There was no significant difference in HPA axis activity between those with somatic KCNJ5 mutation compared to those without.

Evaluation of Neuroendocrine and Immunological Parameters in Animals Following Chronic Combined Exposure to Xenobiotics

Background: A high prevalence of chromium and benzene compounds in the environment associated with motor vehicle and industrial operations arouses interest in the study of these xenobiotics in a long-term experiment. The objective of this work was to analyze effects of a chronic combined exposure to chromium and benzene on the hypothalamic-pituitary-adrenocortical (HPA) and immune systems of male Wistar rats. Materials and methods: Eighty male Wistar rats were administered potassium dichromate and benzene with drinking water in doses equaling one maximum permissible concentration (MPC) during 135 days. The hypothalamus, pituitary gland, adrenal glands, thymus, and spleen were then studied using morphometric, histological, and electron microscopy methods. The streptavidin-biotin peroxidase method was used to determine the expression of pro-apoptotic protein p53 and anti-apoptotic protein bcl2. We also measured the body, thymus and spleen weights of animals, nucleated cell counts in the thymus, spleen, and bone marrow and evaluated the cellular composition of the spleen and bone marrow as well as spontaneous and concanavalin A-induced secretion of interferon gamma (IFN-γ), IL-4, IL-6, and IL-10 cytokines by splenocytes. Results: We established an adverse effect of the exposure on the HPA function expressed in the activation of its secretory activity, blocking the release of hypothalamic neuropeptides at the level of the neurohypophysis and leading to ultrastructural damage to the neurosecretory cells of the hypothalamus, pituitary adenocytes and adrenal cortical cells, as well as in an increase in the programmed death of thymocytes. We also observed a decrease in the thymus weight and thymocyte counts and a complex of structural and functional changes indicating the status of its accidental involution in the exposed rats. The revealed decrease in the splenocyte count in the experimental group was accompanied by an increase in the size of the white spleen pulp. An increase in the induced production of the main immunoregulatory cytokines IFN-γ and IL-4 by splenocytes was found. Conclusion: Our findings can be used to analyze impairments of the HPA and immune systems in workers with a chronic combined exposure to benzene and chromium compounds in the occupational setting.

Activation of PPG neurons following acute stressors differentially involves hindbrain serotonin in male rats

Within the hindbrain, serotonin (5-HT) functions as a modulator of the central glucagon-like peptide-1 (GLP-1) system. This interaction between 5-HT and GLP-1 is achieved via 5-HT2C and 5-HT3 receptors and is relevant for GLP-1-mediated feeding behavior. The central GLP-1 system is activated by various stressors, activates the hypothalamic pituitary adrenocortical (HPA) axis, and contributes to stress-related behaviors. Whether 5-HT modulates GLP-1's role in the stress response in unknown. We hypothesized that the serotonergic modulation of GLP-1-producing neurons (i.e., PPG neurons) is stimuli-specific and that stressed-induced PPG activity is one of the modalities in which 5-HT plays a role. In this study, we investigated the roles of 5-HT2C and 5-HT3 receptors in mediating the activation of PPG neurons in the nucleus tractus solitarius (NTS) following exposure to three different acute stressors: lithium chloride (LiCl), noncontingent cocaine (Coc), and novel restraint stress (RES). Results showed that increased c-Fos expression in PPG neurons following LiCl and RES—but not Coc—is dependent on hindbrain 5-HT2C and 5-HT3 receptor signaling. Additionally, stressors that depend on 5-HT signaling to activate PPG neurons (i.e., LiCl and RES) increased c-Fos expression in 5-HT-expressing neurons within the caudal raphe (CR), specifically in the raphe magnus (RMg). Finally, we showed that RMg neurons innervate NTS PPG neurons and that some of these PPG neurons lie in close proximity to 5-HT axons, suggesting RMg 5-HT-expressing neurons are the source of 5-HT input responsible for engaging NTS PPG neurons. Together, these findings identify a direct RMg to NTS pathway responsible for the modulatory effect of 5-HT on the central GLP-1 system—specifically via activation of 5-HT2C and 5-HT3 receptors—in the facilitation of acute stress responses.

Naloxone-induced conditioned place aversion score and extinction period are higher in C57BL/6J morphine-dependent mice than in Swiss: Role of HPA axis

Intense associative memories develop between drug-paired contextual cues and the drug withdrawal associated aversive feeling. They have been suggested to contribute to the high rate of relapse. Our study was aimed to elucidate the involvement of hypothalamic-pituitary-adrenocortical (HPA) axis activity in the expression and extinction of aversive memory in Swiss and C57BL/6J (B6) mice. The animals were rendered dependent on morphine by i.p. injection of increasing doses of morphine (10–60 mg/kg). The negative state associated with naloxone (1 mg/kg s.c.) precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. B6 mice obtained a higher aversion score and took longer to extinguish the aversive memory than Swiss mice. In addition, corticosterone levels were increased after CPA expression. Moreover, corticosterone levels were decreased during CPA extinction in Swiss mice without changes in B6 mice. Pre-treatment with the selective CRF1 receptor antagonist CP-154,526 before naloxone, impaired morphine-withdrawal aversive memory acquisition and decreased the extinction period. CP-154,526 also antagonized the increased levels of corticosterone observed after CPA expression in Swiss mice, without any changes in B6 mice. These results indicate that HPA axis could be a critical factor governing opioid withdrawal memory storage and retrieval, but in a strain or stock-specific manner. The differences observed between Swiss and B6 mice suggest that the treatment of addictive disorders should consider different individual predisposition to associate the aversive learning with the context.

The persistent associations between early institutional care and diurnal cortisol outcomes among children adopted internationally.

Young children in institutional care experience conditions that are incompatible with their needs for attachment relationships. As a result, early institutionalization is expected to have lasting effects on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The current study tested whether early institutionalization has persistent consequences for diurnal HPA axis outcomes among 130 children who had been adopted internationally between the ages of 6 and 48months. Daily cortisol samples were collected from children at two time points: shortly after adoption (average of 5.3months after adoption) and approximately 3years later (average of 39.2months after adoption). Shortly after adoption, children who had experienced a long duration of institutional care had lower morning cortisol levels and more blunted declines in cortisol across the day than children who experienced minimal or no institutional care. Three years later, children who had experienced a long duration of institutionalization continued to exhibit low morning cortisol levels and also exhibited low bedtime cortisol levels. Altogether, these results support the idea that early adversity results in the downregulation of the HPA axis and suggest that the effects of institutionalization on HPA axis functioning may persist several years after children are adopted into highly enriched families.

A comparative study of adrenalin and fluocinolon induced oxidative stress in male wistar rats

Hormone secretion by the hypothalamic-pituitary-adrenocortical (HPA) axis is modulated by multiple factors which include the circadian rhythm, various types of stressors and glucocorticoids. Treatment with synthetic glucocorticoids as e.g. dexamethasone or dermocorticosteroids and repeated immobilization stress, decreases the total body weight gain of animals by disturbing the HPA axis function and accelerating the catabolism of the organism. Synthetic glucocorticoids are widely used as anti-inflammatory and anti-allergic drugs. Neverteheless, their administration may cause side effects in the normal functioning of several organs. Starting from the above findings and from the important physiological roles of the glucocorticoids in the metabolism, we investigated the reactions of the adrenal and thymus, the evolution of the body and organ weight and the level of the free radicals after adrenaline- and fluocinolon stress. In this study, we used electron paramagnetic resonance spectroscopy for the direct detection of free radical content in the organs o f stressed Wistar rats. We followed the changes of the blood glucose level, body weight,structural modification and whole redox state of the rats during adrenaline and Fluocinolon-acetonid N treatment, as endogenous and exogenous sources of elevated glucocoticoid levels. We found a relationship between changes of the redox state and modified homeostasis of the organism, as an effect of elevated glucocorticoid levels. The oxidative stress induced by adrenalin treatment seemed to be an inducer rather than the result of the tissue damage.

Childhood adversity and cortisol habituation to repeated stress in adulthood

BackgroundChildhood adversity is a robust predictor of poor health outcomes in adulthood and hypothalamic-pituitary-adrenocortical (HPA) axis dysfunction may be a key mechanism explaining this association. However, little is known about the influence childhood adversity may exhibit on adult HPA axis habituation (i.e., decreased cortisol output in response to a repeated stressor), where HPA axis dysfunction can be inferred if habituation deviates from normal patterns. MethodsThe current study used data from a larger study that examined the effects of stress management interventions on cortisol habituation to repeated stress. Eighty-three adults reported childhood adversity with the Adverse Childhood Experience scale and completed the Trier Social Stress Test (TSST) twice (48 h apart) scheduled after a 6-wk intervention period. Salivary cortisol was assessed pre-stressor and +25, +35, and +60 mins post-stressor onset during both visits. ResultsResults indicated that childhood adversity was associated with a marginally larger decrease in total cortisol from visit 1 to visit 2 among men (i.e., habituation), but not women (i.e. non-habituation). ConclusionsThese findings suggest that childhood adversity may alter HPA axis habituation to repeated stress later in life, with possible sex differences. Future research should investigate whether HPA axis habituation to repeated stress may be a pathway through which childhood adversity affects adult health, and how it may affect men and women differently.

Validation of an online version of the Trier Social Stress Test in a study of adolescents

IntroductionThe Trier Social Stress Test (TSST) is the most widely used protocol for activating a stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis and other stress-mediating systems. A number of variants of the TSST exist, including ones for children, groups, and virtual reality. All of these versions, though, require in-person assessment. The COVID-19 pandemic has made in-person assessment impossible or extremely difficult and potentially dangerous. The purpose of this study was to validate a completely remote, online, version of the TSST for children. MethodA sample of 68 (27 female) 15- and 16-year old participants were administered the TSST-Online (TSST-OL) during the late afternoon hours (3–6 p.m. start time). The participants, judges (one male, one female), and experimenter (female) all joined the assessment from their own homes via the online platform, ZOOM™. Two sessions were conducted, one to obtain consent, explain procedures, work with the family to arrange the computer and room set-up for the TSST-OL and one within two weeks to conduct the procedure. The participants were trained to take their own saliva samples and a saliva sampling kit was mailed to the home in between the first and second session. The samples were then mailed to the researchers within a day of collection. The participant was observed during saliva collection to determine correct procedures were followed. Salivary cortisol, salivary α-amylase and self-reports of stress were measured multiple times over the second session. ResultsrmANOVAs yielded a significant effect of trials, for cortisol, F(1.37,90.46) = 15.13, p = .001, sAA, F(2.75,146.68) = 6.91, p = .001, and self-rated stress, F(3.43,222.69) = 118.73, p = .001. There were no significant sex by trials interactions for any measure, although females reported more stress than males, F(1,65) = 9.14, p = .004. For cortisol, from baseline to expected peak (30 min after the onset of speech preparation), the Cohen’s effect size was dz = 0.57. Using 1.5 nmol/l (or 0.54 μg/dl) as the criterion for a response (Miller, Plessow, Kirschaum, & Stalder, 2013), 63% of the participants produced a significant increase in cortisol. ConclusionsThe responses to the TSST-OL are consistent with in-person responses among children and adolescents (see recent meta-analysis (Seddon et al., 2020). The protocol is a viable way of assessing reactivity of the HPA axis and other stress systems without needing to bring the participant into the research laboratory. This method will be useful during periods of widespread infection. It should also work to study populations who all live too far from the research laboratory to be assessed in person.

The possible association between COVID-19 and postural tachycardia syndrome

The possible association between COVID-19 and postural tachycardia syndrome

Hair cortisol in captive corral-housed baboons

Hair cortisol concentrations (HCCs) are measures of long-term hypothalamic-pituitary-adrenocortical (HPA) activity and can be used as indicators of chronic stress. However, intrinsic factors such as an animal’s age and sex can also have an impact on resulting HCCs. Although baboons are commonly studied in captivity, little is known about baseline HCC in this population. Here we measured HCC in two same-sex groups of captive olive (Papio hamadryas anubis) baboons and olive/yellow baboon (Papio hamadryas cynocephalus) crosses housed in large outdoor corrals, and we assessed the impact of age and sex on HCC as major variables of interest. Hair was gently shaved from the back of the neck when the animals were sedated for routine physicals. Subjects were divided into three age categories: juvenile (2–4 years), adult (9–12 years), and senior (13–19 years). The “senior” category contained only males. Results confirm an effect of sex and age on HCCs. Females had higher levels of hair cortisol than males, and juveniles had higher levels than adults. There was also a significant sex × age interaction. There were no sex differences in HCCs in juveniles, but there was a greater decline in HCCs in adult males than in adult females. Within males, there was a significant difference in levels of hair cortisol across the three age categories. Juveniles had higher levels than did adults and seniors, but adults and seniors were not significantly different from one another. These results provide baseline measures of hair cortisol in captive baboons and demonstrate effects of sex and age on HCCs.

Biochemical markers and haemodynamic changes of stress response after intubation with direct laryngoscopy versus video laryngoscopy versus fiberoptic intubation: A comparative study

Laryngoscopy and intubation leads to stimulation of pharyngeal and tracheolaryngeal nociceptors resulting in haemodynamic stress response (HDSR). Stress response is regulated by two primary neuroendocrine systems- the hypothalamus pituitary adrenocortical (HPA) and sympathetic adrenomedullary (SAM) system. Salivary alpha-amylase (SAA) level can be used as an index of the SAM activity, and serum cortisol as an index of HPA activity. This study was aimed to compare three different intubation techniques namely Macintosh laryngoscope, Video laryngoscope and Fiberoptic bronchoscope to observe stress response. This prospective, comparative and observational study was carried out at 120 patients undergoing various elective surgeries under general anaesthesia. Patients were allocated after randomization into three study groups- Group D (Direct laryngoscope), Group V (Video laryngoscope) and Group F (Fiberoptic bronchoscope) with 40 patients in each. Saliva and venous blood samples were collected before inducing the patients and 5-minutes after intubation. Blood pressure, heart rate and saturation were monitored at fixed intervals.A significant difference was observed in the post-intubation values (p=0.0001) of salivary alpha amylase levels by direct laryngoscopy and fiberoptic laryngoscopy, while it was insignificant in video laryngoscopy (p=0.919). Post intubation cortisol level was significantly high in all three groups. However, on group comparison of mean differences of serum cortisol levels, a significant mean difference was seen between D vs V group (p=0.0001), and V vs F group (p=0.0001), while it was not significant in D vs F group (0.157). In addition, changes in mean arterial pressure and heart rate, at 1- and 5-min post- intubation were least in group V. Video laryngoscopy is a safe, and reliable technique. Moreover, it causes lesser stress response to patients in comparison to direct laryngoscopy and fiberoptic groups.

Ablation of NPFFR2 in Mice Reduces Response to Single Prolonged Stress Model

Mental stress is highly related to many clinical symptoms and disorders, as it activates the hypothalamic-pituitary-adrenocortical (HPA) axis to affect a wide variety of physiological functions. Furthermore, stress leads to the aberrations in HPA axis activity and disruptions of body homeostasis. It was previously shown that neuropeptide FF (NPFF) regulates the HPA axis through the activation of hypothalamus paraventricular nucleus (PVN), and genetic overexpression or pharmacological stimulation of NPFF receptor 2 (NPFFR2) triggers hyperactivity of HPA axis and suppresses behavioral correlates of emotion in mice. In this study, we further examined the role of NPFFR2 in stress response in mice by utilizing a single prolonged stress (SPS). SPS is considered a model of post-traumatic stress disorder (PTSD), and mice undergo physical restraint, forced swimming, and ether anesthesia within a day followed by social isolation for one week. NPFFR2 knockout B6 mice were generated by CRISPR/Cas9 technology and exposed to SPS. The NPFFR2 knockouts showed resistance to stress exposure-induced anxiety-like behaviors and HPA axis hyperactivity. Additionally, the hippocampal mRNA levels of glucocorticoid receptor and mineralocorticoid receptor were reduced in wild-type (WT) mice but not in NPFFR2 knockouts after stress exposure. Our data also suggested that NPFFR2 knockout mice have stronger negative feedback on the HPA axis after exposure to SPS. Mice with intra-PVN Npffr2 shRNA injection displayed trends toward resistance to SPS exposure in both behavioral and molecular assays. Together, our findings suggest that NPFFR2 may be a potential therapeutic target for disorders relating to stress/anxiety and HPA dysregulation.

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings

Polymorphisms of genes involved in the hypothalamic–pituitary–adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6–8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C–rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.

Pubertal recalibration of cortisol reactivity following early life parent-child separation

BackgroundThe hypothalamic–pituitary–adrenocortical (HPA) axis had been proved to calibrate to early-life adversity and puberty may reverse the calibration. This study examines the consequences of prolonged parent-child separation on HPA axis reactivity and the pubertal recalibration hypothesis. MethodsTotally of 144 participants aged 8.75 to 15.25 (mean age 12.50 years, SD: 1.32) were enrolled from rural areas of Chizhou city, Anhui Province of China in 2019. Data on parent-child separation was collected from parents. Self-reported Peterson Pubertal Development Scale was used to assess pubertal maturation and HPA axis stress reactivity was measured using the Trier Social Stress Test for Children. ResultsFor children at early stage of puberty, childhood parent-child separation experiences were associated with blunted HPA axis reactivity (B = -1.888, p = 0.034); while for those at later stage of puberty, HPA axis reactivity was similar between children experienced early childhood separation and those without separation (AUCi: B = -0.426, p = 0.878). In contrast, for children experienced persistent parent-child separation, blunted HPA axis reactivity was observed (all p < 0.05). LimitationsDue to the cross-sectional nature of this study, conclusions about causality remain speculative. ConclusionsThe effect of parent-child separation on dysregulation of HPA axis acts in a time-dependent manner. This finding provides support for the pubertal recalibration hypothesis suggesting that a focus of improving environment in adolescence would help those individuals reared initially in non-supportive conditions.

The condition of neuro-endocrine systems in acute experimental myocardial infarction against the background of various reactivity of the organism

The adequacy of recovery processes in myocardial infarction (MI) significantly depends on the state of reactivity of the organism, which, in turn, is determined by the adequacy of neuro-endocrine regulation, in particular, hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-thyroid (HPT) system system.Purpose of the study. To investigate the condition of HPA and HPT in acute experimental MI against the background of different reactivity of the organism.Material and methods. The study was performed on 20 outbred adult dogs weighing 8-12 kg, in which MI was simulated by ligation of the anterior interventricular artery. Animals were divided into three groups (n =5 in each group). The condition of hyperreactivity was caused by the introduction of pyrogenal (group 2), the state of hyporeactivity - the introduction of azothioprine (group 3), in group 1 drugs were not used (state of normoreactivity). In the control group used 5 falsely operated dogs with thoracopericardiotomy. In animals before surgery, on 1, 4, 7, 11 and 15 days in the blood was determined by the content of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) , cortisol (Cr), aldosterone (Ald), thyroxine and triiodothyronine. Statistical processing was performed using license packages Statistica 5.5 (Stat Soft Rus), Statistica Neural Networks (Statsoft Inc.).Results. Normoreactive course of myocardial infarction was characterized by primary activation of HPA, which was most pronounced for Cortisol, followed by restoration of ACTH and Aldosterone levels and duration of activation of the central link up to 4 days, peripheral - up to 7-11 days; reciprocal in relation to HPA inhibition of the functional activity of the HPT, most pronounced on the 4th day and lasting up to 15 days. Such changes caused the healing of myocardial infarction through the formation of a full-fledged post-infarction scar. The hyperreactive course of myocardial infarction was characterized by hypersecretion of ACTH with hypercorticism and hyperaldosteronism and less pronounced suppression of HPT with the restoration of its functional activity on the 7th day. The hyporeactive course of myocardial infarction was characterized by a minimally pronounced and delayed up to 4 days activation of HPA with Aldosterone hyposecretion on the 15th day; deep hypothyroidism of both central and peripheral genesis. Impaired reactivity was accompanied by an increase in the area of necrosis and a decrease in the thickness of the heart wall with the formation of postinfarction aneurysm.Conclusions. Desynchronization of necrotic and reparative processes with a change in reactivity leads to a disruption in the relationship between necrosis and repair with the formation of postinfarction aneurysm, which is accompanied by different activities of the HPA and HPT.

Corroborative evidence for an association between initial hypothalamic-pituitary-adrenocortical axis reactivity and subsequent habituation in humans

BackgroundThe extant literature predicts that initial hypothalamic-pituitary-adrenocortical (HPA) axis response magnitude and subsequent habituation are associated with health, such that both heightened stress reactivity and non-habituation to repeated stressors are associated with disease. Yet, despite evidence for an association between initial HPA axis reactivity and subsequent habituation, the extant literature often considers health implications of these stress response patterns independently or make interpretations based on an initial response alone. This may be because past tests of the association between reactivity and habituation were subject to statistical bias (e.g., regression to the mean), and no prior work has examined the association between initial cortisol reactivity and subsequent habituation using analytic strategies capable of estimating the unbiased relationship between initial value (i.e., reactivity) and subsequent change (i.e., habituation). Accordingly, the present investigation drew from two previously published studies to test the association between initial HPA axis reactivity and subsequent habituation using analytic strategies capable of estimating the relationship between initial reactivity and subsequent habituation with minimal bias. MethodsWe examined salivary cortisol and plasma ACTH responses to three repeated social-evaluative stressors (Study 1) and salivary cortisol responses to two repeated social-evaluative stressors (Study 2). ResultsAs predicted, results indicated a negative relationship (Pearson’s r ranging from -0.27 to -0.91) where initial HPA axis reactivity was associated with subsequent habituation across both studies, even when using estimation procedures capable of producing an unbiased estimate of this relationship. ConclusionsResults support the claim that initial HPA axis reactivity to acute stress is associated with subsequent habituation, such that initially high reactors are likely to habituate, whereas initially blunted reactors are likely to sensitize. In view of these results, hypothesized long-term health implications of acute cortisol reactivity and habituation patterns should be considered in tandem.

Prenatal maternal stress and child hair cortisol four years later: Evidence from a low-income sample

BackgroundMaternal stress during pregnancy can influence the trajectory of fetal development, shaping offspring physiology and health in enduring ways. Some research implicates fetal programming of the hypothalamic-pituitary-adrenocortical (HPA) axis as a mediator of these effects. The present study is the first to examine child hair cortisol concentration (HCC) and maternal stress during pregnancy in a diverse, low-income sample. MethodsThe sample consisted of 77 healthy, low-income (M annual income: $13,321), mother-children pairs (M child age = 3.81 years, SD = 0.43). The children were 57 % girls, 43 % boys. Mothers were 65 % Latina/Hispanic, 28 % Non-Hispanic White, 7% Black/African American. Maternal prenatal stress was measured with the Perceived Stress Scale administered by interview in the second and third trimesters, and again approximately four years later when child hair samples for assaying HCC were collected. ResultsOn average maternal perceived stress increased significantly across pregnancy, then returned to lower levels 4 years after birth. Regression analysis revealed that child HCC was not significantly predicted by maternal perceived stress at either single prenatal time point. Exploratory analysis revealed evidence of a relation between increases in maternal prenatal stress from second to third trimester and child HCC four years later (r = .37, p = .04). ConclusionsThese results suggest that measures of prenatal maternal stress at any one time point may not be predictive of offspring long-term HPA output in low-income child samples, but that increases in stress levels across pregnancy may provide important information undetected by individual time point measures.

Social Integration and Diurnal Cortisol Decline: The Role of Psychosocial and Behavioral Pathways.

A growing number of studies have associated various measures of social integration, the diversity of social roles in which one participates, with alterations in hypothalamic-pituitary-adrenocortical (HPA) functioning. The pathways through which social integration may be linked to HPA functioning, however, are as yet unknown. The present study examined whether daily social interactions, affective responses, health behaviors, and personality help explain the association between social integration and diurnal cortisol slope. A sample of 456 healthy, employed adults (53.9% female, 82.0% white, 72.2% bachelor's degree or greater, mean age of 42.86 years) completed a 4-day ecological momentary assessment protocol that measured cortisol, social interactions, affect, sleep, and physical activity at frequent intervals throughout the day. Social integration was measured at baseline. Regression results controlling for age, sex, race, and education indicated that more socially integrated individuals showed steeper cortisol slopes (B = -0.00253, p = .006). Exploratory analyses suggested that the consistency (i.e., reduced variability) in nightly sleep midpoint partially explained this association (B = -0.00042, 95% confidence interval = -0.00095 to -0.00001). Personality, mood, social interaction patterns, and nonsleep health behavior differences did not account for the association between social integration and HPA activity. This study replicates previous findings linking social integration and HPA functioning, and it examines patterns of nightly sleep as possible pathways through which the association may operate. Results have implications for understanding mechanisms for health risk and for development of future interventions.

A Moderate Increase in Ambient Temperature Influences The Structure and Hormonal Secretion of Adrenal Glands in Rats.

Objective As a consequence of global warming, the increase in the average annual temperature is observed, while the living organisms actively adapt to these changes. High environmental temperature initiates numerous physiological, autonomic, and behavioral responses, and activates the stress response. Thus, the aim of the study was to investigate effect of a moderate increase in ambient temperature on the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis by determining histological changes in adrenal glands and hormonal levels in adult male rats. Material and Methods: In this experimental study, the morpho-functional state of adrenal glands was estimated by stereological evaluation of parameters, including the adrenal volume, adrenocortical cell/nuclear size and number, and the volume density of vascular tissues after four days of exposure to a moderate increase in ambient temperature of 35 ± 1˚C. Novelli histochemical and vascular endothelial growth factor (VEGF) immunohistochemical staining provided insight into the adrenal gland vascular network. Additionally, the adrenal levels of aldosterone, corticosterone, and pituitary adrenocorticotropic hormone (ACTH) were determined as crucial indicators of the hypothalamic-pituitary- adrenocortical (HPA) axis activity. Results Prolonged exposure to a moderate increase in ambient temperature for four days resulted in a significant increase in ACTH level up to 24%, which altered adrenal glands both structurally and functionally. The adrenocortical volume and number of cells in all cortical zones were markedly increased (P<0.05). A statistically significant increase was shown in the level of aldosterone (16%) and corticosterone (25%) in serum levels of individuals. ConclusionIncreased activity of the HPA axis reflects the response to a moderate increase in ambient temperature during four days, showing the capacity of the HPA axis to adapt the organism to daily temperature changes.

Working Memory Predicts Hypothalamus-Pituitary-Adrenal Axis Response to Psychosocial Stress in Males.

The hypothalamic-pituitary-adrenocortical (HPA) function is crucial for adaptation to stress and recovery of homeostasis. Physiological alteration in the HPA axis has been shown to play a pivotal role in the generation of stress-related disorders. A growing number of studies have begun to identify which variables are possible to predict individual HPA response and associated stress vulnerability. The current study investigated the relationship between working memory and the subsequent magnitude of HPA response to psychosocial stress in a non-clinical population. Working memory was assessed utilizing an n-back task (2/3-back) in thirty-nine healthy young men, whose electroencephalograms were recorded. The HPA response was measured using the percentage increase in cortisol to an acute psychosocial stress protocol called the Trier Social Stress Test (TSST). Our results show that longer reaction time and smaller amplitude of P2 predict a relatively lower HPA response to stress. Our study provides new insights into how neurocognitive factors can be used to predict HPA response to acute stress.