Hypothalamic-pituitary-adrenal System Activity Research Articles

Childhood trauma: A factor for increased risk of major depression in psoriatic patients

A history of childhood maltreatment (CM) is an important determinant for understanding the development of psychiatric and physical disorders. CM is associated with sensitization of central nervous system (CNS) that leads to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis [1]. Early life stress is a well-known contributor to major depression [2]. The dysregulation of HPA axis and sympathetic nervous system activity also impact skin. Epidermis shows a high vulnerability to such psychological stressors resulting to increase risk for psoriasis [3]. The current study investigates the association between childhood trauma and major depression, childhood trauma and psoriasis, and also severity of major depression in female and male patients with psoriasis. Sixty-four psoriatic patients (female = 34, mean age = 46.87) were evaluated with the Childhood Trauma Questionnaire (CTQ) for the history of CM and with the MINI International Neuropsychiatric Interview for the diagnosis of major depression. CM was associated with major depression, indexed by a higher CTQ in emotional (χ2(3) = 26.002, P < .0005) and physical abuse scores (χ2(3) = 23.764, P < .0005). CM limited to sexual abuse was associated with higher severity of psoriasis (χ2(3) = 9.81, P < .02). There was no indication of a difference between men and women in severity of major depression (U = 444, P = .304). Our findings highlight the importance of recognizing psychiatric comorbidity, in particular major depression, among psoriatic patients. Depressive disorder with the presence of psoriasis may constitute a separate etiology with a greater contribution of early environment.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Hypothalamic-Pituitary-Adrenocortical Dysfunction in Elderly, Male Marathon Runners: Feedback Sensitivity, Stress Response, and Effects on Verbal Memory

Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system at a suprapituitary level, and to impaired mnemonic function. We compared cognitive tests, as well as feedback integrity and stress responsivity of the HPA system, between 11 elderly, male marathon runners - a model of repeated HPA system activation - and 10 sedentary controls. The marathon runners had significantly increased baseline, stress, and post-stress ACTH - but not cortisol - concentrations. Also, suppression of ACTH by 3 mg dexamethasone was impaired in the athletes compared to the control subjects, while the ACTH and cortisol response to additional CRH did not differ between the 2 groups. Finally, long-term verbal memory was impaired in the athletes compared to the controls. Regarding the HPA system, these findings are in accordance with an acquired suprapituitary feedback disturbance in marathon runners; however, the similar glucocorticoid concentrations in the 2 groups may be due to reduced adrenal sensitivity to ACTH. Together with impaired verbal memory, these data support the assumption that repeated episodes of HPA system activity may exert negative effects at the level of the hippocampus.

Hypercortisolemic Depressed Women: Lean but Viscerally Obese?

Background: Activation of the hypothalamic-pituitary-adrenal (HPA) system in depressed patients has been related to visceral adiposity. In contrast, low HPA system activity is associated with increased body fat in the general population. Our study intended to clarify whether HPA system activity is related to body weight and composition in depressed inpatients. Methods: In a cohort of 51 female and 20 male depressed inpatients, we measured saliva cortisol (HPA system activity), body mass index (BMI), waist circumference as well as body composition as reflected by bioimpedance. Results: In female patients, cortisol in saliva was negatively associated with fat-to-muscle ratio and BMI. Conclusion: In depressed inpatients, especially women, there is evidence that activation of the HPA system is related to relatively low body weight and low body fat content.

The relationship between neuroendocrine dysfunction and free-radical oxidation in old age alcoholism

to study the relationship between dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and free-radical oxidation in old age alcoholism. Authors examined 46 men and women, aged 60-80 years, with alcoholism. Contents of cortisol, lipid peroxidation products and the level of an oxidatively modified protein were measured. A decrease in blood cortisol content and correlations between its level and activity of free-radical oxidation were identified. The severity of neuroendocrine dysfunction in old patients was sex-related. It has been suggested that the impairment of HPA system activity may be a cause of oxidative stress and development of alcoholism.

PCLO rs2522833 impacts HPA system activity in healthy young adults

Recent genetic studies showed evidence for a role of the single-nucleotide polymorphism rs2522833 within the PCLO gene in the etiology of major depression, and rs2522833 has been shown to modulate hypothalamic pituitary adrenal (HPA) axis activity during antidepressant treatment. Monoaminergic modulation of the HPA system may be one possible pathomechanism by which PCLO exerts its effect on depression. In the present study, we investigated the effect of rs2522833 on the cortisol awakening response (CAR) in healthy young adults. A total of 66 healthy volunteers from the community (36 men and 30 women) aged 18–25 years without individual or family history of affective disorders and schizophrenia collected saliva cortisol samples at 0, 30, 45 and 60 min after awakening on two consecutive working days. We identified a blunted CAR (AUCinc) in rs2522833 risk-allele (C) carriers, possibly indicating exhausted regulatory mechanisms underlying the HPA system. We also identified higher neuroticism scores in rs2522833 risk-allele carriers but no phenotypic correlation between the CAR (AUCinc) and neuroticism. These findings suggest that the rs2522833 risk variant might increase vulnerability to depression both by physiological and behavioral pathways, which appear, however, not to be substantially overlapped. Replication with larger samples is warranted.

Restless legs syndrome: Evidence for nocturnal hypothalamic‐pituitary‐adrenal system activation

Epidemiological studies consistently point to a relationship between restless legs syndrome (RLS) and cardiovascular disease. The mechanism underlying this association is unclear. Activation of the hypothalamic-pituitary-adrenal (HPA) system has been shown to contribute to the metabolic syndrome and an enhanced cardiovascular risk. We investigated cortisol levels as an indicator of HPA system activity in RLS during the nighttime, when RLS symptoms are at their maximum. We assessed nocturnal urinary cortisol excretion in 73 patients with RLS and 34 healthy controls, controlling for age and gender. Urine sampling was paralleled by polysomnographic recordings. We found significantly enhanced nocturnal cortisol excretion in RLS, demonstrating nocturnal HPA system overactivity in RLS. HPA system overactivity is a possible mechanism contributing to the enhanced load of cardiovascular disease in RLS patients. Nocturnal cortisol release showed weak correlations with some polysomnographic parameters of disturbed sleep, making a potential contribution of RLS-induced sleep disruption to HPA system activation conceivable.

Noninvasive approach to the assessment of activity of the hypothalamic-pituitary adrenal system of the Amur tigers

The state of animals in natural populations can be often assessed only by noninvasive methods. The use of EIA antibodies against corticosterone makes it pos� sible to reveal an increase in the concentration of immunoreactive compounds that bind to antibodies against corticosterone in faeces of tigers both after artificial stimulation of adrenal glands by injection of adrenocorticotropic hormone and after stress (trans� portation of animals). This confirms the possibility of using antibodies against corticosterone for noninva� sive monitoring of the state of the hypothalamicpitu� itaryadrenal system (HPAS) in Amur tigers. The Amur tiger ( Panthera tigris altaica) is a subspe� cies inhabiting the periphery of the species range under conditions that are suboptimal for this species. In this case, exposure to adverse factors with a higher probability may cause an increase in the activity of the hypothalamicpituitaryadrenal system (HPAS), which may suppress breeding and even result in ani� mal's death. Rehabilitation of tigers withdrawn from nature and their subsequent return to natural environ� ment becomes a relevant method to conserve this spe� cies. However, these operations are associated with transportation of animals, which is a strong stressor. With allowance for the fact that the abundance of the Amur tiger is very low (approximately 500 animals (1)), establishing the factors that endanger this species and determination of the effect of transportation on the stress level of animals are very important for con� servation of Amur tigers and development of rehabili� tation programs for these animals. The welfare of animals is estimated primarily by the HPAS activity, because adverse factors stimulate it and cause an increase in the level of glucocorticoids in blood plasma. Changes in the concentration of gluco� corticoids (first of all, cortisol and corticosterone) in blood plasma compared to their baseline level can serve as a reliable indicator of animal's state. At the same time, this method has serious limitations: stress procedures, such as capture, handling, and immobili� zation of animals as such often drastically increase the level of glucocorticoids in blood plasma of animals and leads to a bias in results, because in this case only the response to manipulations is recorded (2).

82. Application of repeated social stress to pregnant gilts during early or late gestation differentially affects HPA axis and immune system activity of the piglets

Early life stress (ELS) affects facial emotion recognition (FER), as well as the underlying brain network. However, there is considerable inter-individual variability in these ELS-caused alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is assumed to mediate neural and behavioural sequelae of ELS, the genetic disposition towards HPA axis reactivity might explain differential vulnerabilities.An additive genetic profile score (GPS) of HPA axis reactivity was built from 6 SNPs in 3 HPA axis-related genes (FKBP5, CRHR1, NR3C1). We studied two independent samples. As a proof of concept, GPS was tested as a predictor of cortisol increase to a psychosocial challenge (MIST) in a healthy community sample of n = 40. For the main study, a sample of n = 170 completed a video-based FER task and retrospectively reported ELS experiences in the Childhood Trauma Questionnaire (CTQ).GPS positively predicted cortisol increase in the stress challenge over and above covariates. CTQ and genetic profile scores interacted to predict facial emotion recognition, such that ELS had a detrimental effect on emotion processing only in individuals with higher GPS. Post-hoc moderation analyses revealed that, while a less stress-responsive genetic profile was protective against ELS effects, individuals carrying a moderate to high GPS were affected by ELS in their ability to infer emotion from facial expressions.These results suggest that a biologically informed genetic profile score can capture the genetic disposition to HPA axis reactivity and moderates the influence of early environmental factors on facial emotion recognition. Further research should investigate the neural mechanisms underlying this moderation. The GPS used here might prove a powerful tool for studying inter-individual differences in vulnerability to early life stress.

Dysfunktion des Hypothalamus-Hypophysen-Nebennierenrinden-Systems - Hintergrundvariable relevanter kardiovaskulärer Risikofaktoren?

The present project is based on findings showing that important risk factors for the development of coronary heart disease are frequently associated with a dysregulation in stress-responsive systems. Accordingly, the observed dysfunction in these systems might represent a background variable with a significant effect on the development and course of coronary heart disease. Examining a random population sample we aim at testing the hypothesis whether cardiac risk factors such as arterial hypertension, type 2 diabetes, visceral obesity and depression might be associated with a dysfunction in a major stress-responsive system, namely the hypothalamic-pituitary-adrenal (HPA) system. Assessment of the functional status of this system will be carried out by measuring cortisol concentrations in saliva at four set measurement times throughout a normal day while subjects continue to carry out their usual activities. This methodology enables us to characterize HPA system activity with regard to basal tone, reactivity to a specific stressor, circadian rhythm and overall activity. Our study population includes 1250 subjects aged 50 to 70 years taken from a representative sample of the general public of the city of Augsburg, Germany (KORA F3). Through close cooperation within the framework of the present project we will be able to examine neuroendocrine issues in association with detailed demographic and clinical data of a representative population sample.

Anna-Monika-Prize paper. The hypothalamic-pituitary-adrenal system in depression.

Patients with depression frequently have symptom clusters which point strongly to involvement of the hypothalamic-pituitary-adrenal (HPA) system as a relay station between neurocircuitries in the brain and peripheral hormone and autonomic nervous function. It has been proposed that this increased, state-dependent hyperactivity of the HPA-system in depression is probably initiated and/or maintained by the combination of enhanced central production of CRH and desensitization of the binary, glucocorticoid receptor binding system in the hippocampus, which is the central regulator of HPA system activity. In a first series of studies a refined neuroendocrine test to probe the integrity of HPA system status--the combined dexamethasone suppression/CRH challenge (DEX/CRH) test--was developed and the differential effects of aging and depressed psychopathology on DEX/CRH test outcome were described. In a second set of studies, the chronological relationship between improvement of psychopathology in depressed patients treated with antidepressants and normalization of the disturbed HPA system function in these patients was further elucidated. Given the evidence from animal studies, we conclude that antidepressants induce an up-regulation of hippocampal glucocorticoid receptor mRNA concentration, thus amplifying the negative feedback effect of glucocorticoids. This then results in the normalization of DEX/CRH test results observed in the depressed patients in our study. We further conclude that dampening of HPA system hyperactivity in depression by means of antidepressants is a conditio sine qua non for successful improvement of psychopathology.

Release of Vasopressin within the Rat Paraventricular Nucleus in Response to Emotional Stress: A Novel Mechanism of Regulating Adrenocorticotropic Hormone Secretion?

The effects of emotional stressors on the release of arginine vasopressin (AVP) and oxytocin (OXT) within the rat hypothalamus and the origin and physiological significance of AVP released within the hypothalamic paraventricular nucleus (PVN) were investigated. First, adult male Wistar rats with a microdialysis probe aimed at the PVN or the supraoptic nucleus were exposed to either a dominant male rat (social defeat) or a novel cage. Release of AVP within the PVN was significantly increased in response to social defeat but not to novelty. In contrast to an activation of the hypothalamic-pituitary-adrenal (HPA) system, neither stressor stimulated the hypothalamic-neurohypophysial system (unchanged plasma AVP and OXT and unchanged release within the supraoptic nucleus [AVP] and the PVN [OXT]). Next, we demonstrated by simultaneous microdialysis of the suprachiasmatic nucleus and the PVN that AVP measured in PVN dialysates during social defeat was probably of intranuclear origin. Finally, a mixture of a V1 AVP and the alpha-helical corticotropin-releasing hormone (CRH) receptor antagonists administered via inverse microdialysis into the PVN caused a significant increase in the plasma adrenocorticotropic hormone (ACTH) concentration compared with vehicle-treated controls both under basal conditions and during social defeat, indicating inhibitory effects of intra-PVN-released AVP and/or CRH on HPA system activity. The antagonists failed to affect anxiety-related behavior of the animals as assessed with the elevated plus-maze. Taken together, our results show for the first time that AVP is released within the PVN in response to an emotional stressor. We hypothesize that this intranuclear release provides a negative tonus on ACTH secretion.

Maternal factors regulate stress responsiveness in the neonatal rat

Experiment 1 compared (basal and stress-induced) adrenocortical secretion in infants individually isolated for a 24-h period with infants deprived of their mothers but in contact with their littermates. Maternal deprivation resulted in the activation of the pups’ hypothalamic-pituitaryadrenal (HPA) system, independent of the social contact with the littermates. Results from Experiment 2 showed that nonnutritional contact with a thelectomized (nipple-removed) dam was only partially effective in suppressing the HPA system activity, and this effect was age dependent. Experiment 3 explored the possibility that glucocorticoids transported through the milk might be involved in the inhibition of the HPA system. Infants that remained with an adrenalectomized dam for 24 h prior to testing did not differ from their nondeprived counterparts on Day 8 but did differ on Day 12, suggesting that, at the older ages, the nutritional demands were greater and that the effects observed were probably due to undernutrition.