HPA axis and aging in depression: systematic review and meta-analysis.: One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We f
HPA axis and cortisol
The hormonal stress response and its measurement.
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المكتبة البحثية897 works heldPeer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.
The HPA axis in bipolar disorder: Systematic review and meta-analysis.: Objectives: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). Methods: Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. Results: Forty-one studies were included in the meta-analyses. BD
Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research.: Objectives: To summarize quantitatively the literature comparing hypothalamic-pituitary-adrenal (HPA) axis function between depressed and nondepressed individuals and to describe the important sources of variability in this literature. These sources include methodological differences between studies, as well as demographic or clinical differences between depressed samples. Methods: The current study used meta-analytic techniques to compare 671 effect sizes (cortisol, adrenocorticotropic hormone,
The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.: According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly traine
Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review.: Background: Although there is substantial evidence of differential hypothalamic-pituitary-adrenal (HPA) axis activity in both generalized and abdominal obesity, consistent trends in obesity-related HPA axis perturbations have yet to be identified. Objectives: To systematically review the existing literature on HPA activity in obesity, identify possible explanations for inconsistencies in the literature, and suggest methodological improvements for future study. Data sources: Included papers used
Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis.: The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol are essential for an adequate response to stress. Considering the role of stress as a risk factor for psychiatric disorders, it is not surprising that cortisol stress reactivity has frequently been investigated in patients versus healthy individuals. However, the large heterogeneity in measures of the cortisol stress response has hampered a systematic evaluation of the evidence. We here report of a systematic literature r
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751 to 775 of 897Fetal growth and the adrenocortical response to psychological stress.
Context: Experimental studies in animals show that adverse prenatal environments lead to lifelong alterations in the activity of the hypothalamic-pituitary-adrenal axis, which mediates the stress response through secretion of glucocorticoid hormones. The extent to which such prenatal hypothalamic-pituitary-adrenal axis adaptations occur in humans is unknown. Objective: The objective of the study was to determine whether smaller but otherwise healthy term babies are more likely to demonstrate increased glucocorticoid responses to psychological stress in childhood. Design and participants: This was a cross-sectional study of 68 boys and 72 girls (aged 7-9 yr) who have been followed up since 12 wk gestation when their mothers took part in a study of healthy children born in Southampton, United Kingdom. Main outcome measure: Salivary cortisol responses to psychological stress were measured. …
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Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial.
Background: Antenatal betamethasone treatment is widely used for the prevention of neonatal respiratory distress syndrome in preterm infants and substantially reduces neonatal mortality and morbidity. Fetal exposure to excess glucocorticoids has been proposed as one of the core mechanisms of the fetal origins of adult disease hypothesis. We assessed whether antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome affects cardiovascular risk factors at 30 years of age. Methods: We followed up at age 30 years 534 individuals whose mothers participated in a double-blind, placebo-controlled, randomised trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Mothers received two doses of betamethasone or placebo given by intramuscular injection 24 h apart. Follow-up assessments included anthropometry; measurement o…
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Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory.
The prefrontal cortex (PFC), a key brain region controlling cognition and emotion, is strongly influenced by stress. While chronic stress often produces detrimental effects on these measures, acute stress has been shown to enhance learning and memory, predominantly through the action of corticosteroid stress hormones. We used a combination of electrophysiological, biochemical, and behavioral approaches in an effort to identify the cellular targets of acute stress. We found that behavioral stressors in vivo cause a long-lasting potentiation of NMDAR- and AMPAR-mediated synaptic currents via glucocorticoid receptors (GRs) selectively in PFC pyramidal neurons. This effect is accompanied by increased surface expression of NMDAR and AMPAR subunits in acutely stressed animals. Furthermore, behavioral tests indicate that working memory, a key function relying on recurrent excitation within netw…
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Role of the primate orbitofrontal cortex in mediating anxious temperament.
Background: Excessive behavioral inhibition during childhood marks anxious temperament and is a risk factor for the development of anxiety and affective disorders. Studies in nonhuman primates can provide important information related to the expression of this risk factor, since threat-induced freezing in rhesus monkeys is a trait-like characteristic analogous to human behavioral inhibition. The orbitofrontal cortex (OFC) and amygdala are part of a circuit involved in the processing of emotions and associated physiological responses. Earlier work demonstrated involvement of the primate central nucleus of the amygdala (CeA) in mediating anxious temperament. This study assessed the role of the primate OFC in mediating anxious temperament and its involvement in fear responses. Methods: Twelve adolescent rhesus monkeys were studied (six lesion and six control monkeys). Lesions were targeted …
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Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain.
Rats repeatedly exposed to restraint show a reduced hypothalamic-pituitary-adrenal axis response upon restraint re-exposure. This hypothalamic-pituitary-adrenal axis response habituation to restraint does not generalize to other novel stressors and is associated with a decrease in stress-induced c-fos expression in a number of stress-reactive brain regions. We examined whether habituation to repeated restraint is also associated with adaptation of immediate early gene expression in brain regions that process and relay primary sensory information. These brain regions may not be expected to show gene expression adaptation to repeated restraint because of their necessary role in experience discrimination. Rats were divided into a repeated restraint group (five 1-hour daily restraint sessions) and an unstressed group (restraint naïve). On the sixth day rats from each group were either killed…
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Adrenal Aging and Its Implications on Stress Responsiveness in Humans.
Normal aging results in subtle changes both in ACTH and cortisol secretion. Most notable is the general increase in mean daily serum cortisol levels in the elderly, without a noteworthy alteration in the normal circadian rhythm pattern. Glucocorticoid excess seen in the elderly population can have serious consequences in both the structural and functional integrity of various key areas in the brain, including the hippocampus, amygdala, prefrontal cortex, with consequent impairment in normal memory, cognitive function, and sleep cycles. The chronically elevated glucocorticoid levels also impinge on the normal stress response in the elderly, leading to an impaired ability to recover from stressful stimuli. In addition to the effects on the brain, glucocorticoid excess is associated with other age-related changes, including loss of muscle mass, hypertension, osteopenia, visceral obesity, an…
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Stress Biomarkers in Biological Fluids and Their Point-of-Use Detection.
Hormones produced by glands in the endocrine system and neurotransmitters produced by the nervous system control many bodily functions. The concentrations of these molecules in the body are an indication of its state, hence the use of the term biomarker. Excess concentrations of biomarkers, such as cortisol, serotonin, epinephrine, and dopamine, are released by the body in response to a variety of conditions, for example, emotional state (euphoria, stress) and disease. The development of simple, low-cost modalities for point-of-use (PoU) measurements of biomarkers levels in various bodily fluids (blood, urine, sweat, saliva) as opposed to conventional hospital or lab settings is receiving increasing attention. This paper starts with a review of the basic properties of 12 primary stress-induced biomarkers: origin in the body (i.e., if they are produced as hormones, neurotransmitters, or b…
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Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer's disease.
Various environmental and genetic factors influence the onset and progression of Alzheimer's disease (AD). Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which controls circulating levels of glucocorticoid hormones, occurs early in AD, resulting in increased cortisol levels. Disturbances of the HPA axis have been associated with memory impairments and may contribute to the cognitive decline that occurs in AD, although it is unknown whether such effects involve modulation of the amyloid beta-peptide (Abeta) and tau. Using in vitro and in vivo experiments, we report that stress-level glucocorticoid administration increases Abeta formation by increasing steady-state levels of amyloid precursor protein (APP) and beta-APP cleaving enzyme. Additionally, glucocorticoids augment tau accumulation, indicating that this hormone also accelerates the development of neurofibrillary ta…
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Microbiota regulate social behaviour via stress response neurons in the brain.
Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut-brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in …
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Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress.
Epigenetic signatures in germ cells, capable of both responding to the parental environment and shaping offspring neurodevelopment, are uniquely positioned to mediate transgenerational outcomes. However, molecular mechanisms by which these marks may communicate experience-dependent information across generations are currently unknown. In our model of chronic paternal stress, we previously identified nine microRNAs (miRs) that were increased in the sperm of stressed sires and associated with reduced hypothalamic-pituitary-adrenal (HPA) stress axis reactivity in offspring. In the current study, we rigorously examine the hypothesis that these sperm miRs function postfertilization to alter offspring stress responsivity and, using zygote microinjection of the nine specific miRs, demonstrated a remarkable recapitulation of the offspring stress dysregulation phenotype. Further, we associated lo…
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Nonapeptide modulation of looming-induced responses in male Betta splendens.
The looming stimulus is a widely used paradigm for investigating defensive behaviours in prey-predator contexts, as it simulates an approaching threat through the rapid expansion of a dark disk. Such stimuli typically evoke fight, flight, or freeze responses. In the present study, the role of the nonapeptides oxytocin and vasotocin, both known for their roles in social behaviour and stress regulation, in the behavioural and endocrine response to a looming stimulus in the Siamese fighting fish Betta splendens was assessed. Fish displayed pronounced freezing behaviour and the expression of conspicuous body stripes in response to a 10-min looming stimulus. Despite the marked behavioural reaction, no concomitant changes in plasma cortisol levels were recorded. The oxytocin receptor antagonist (L-368,899) did not affect the behavioural response, whereas treatment with the vasotocin receptor a…
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Behavioural variability, physical activity, rumination time, and milk characteristics of dairy cattle in response to regrouping.
In the commercial dairy industry worldwide, it is common practice to periodically regroup cows as part of their management strategy within housed systems. While this animal husbandry practice is intended to improve management efficiency, cows may experience social stress as a result of the social environment changes, which may have an impact on their behavioural patterns, performance, and welfare. We investigated whether regrouping altered dairy cows' behaviour and impacted their cortisol concentration (a physiological marker of stress), oxytocin, milk yield, and quality in a robotic milking system. Fifty-two lactating cows (17 primiparous; 35 multiparous) were moved in groups of 3-5 individuals into established pens of approximately 100 cows. Behaviour of the regrouped cows was directly observed continuously for 4 h/day across 4-time blocks (day-prior (d-1), day-of regrouping (d0), day-…
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Biopsychosocial Correlates and Individual Differences for Eliciting Moral Elevation in Veterans With PTSD: An Experimental Case Series.
A promising approach to enhancing trauma-focused treatment is moral elevation-feeling inspired by witnessing a virtuous act. This study explored potential links between eliciting elevation and relevant outcomes in a series of case examples. Veterans with probable posttraumatic stress disorder completed experimental tasks including a written trauma narrative exercise and watching elevation-eliciting videos. Participants also completed baseline assessments, repeated measures of trauma-related cognitions, emotions, elevation, and saliva sample collection. Four cases were identified and reviewed: two positive responders (high elevation after videos) and two nonresponders (restricted elevation response). Positive responder cases reported decreased cognitions, emotions, and moral injury distress from after the trauma narrative to after elevation exercises, whereas nonresponders reported minima…
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The loneliness factor in eating disorders: Implications for psychopathology and biological signatures.
Objectives: Eating disorders (ED) are severe psychiatric conditions. While the biological consequences of EDs are well established, including an increase in inflammatory biomarkers, the influence of psychological factors, such as loneliness, has only recently gained attention in research. Loneliness has been associated with more severe psychopathology in ED patients, while its association with inflammatory biomarkers has only been explored in the general population. For these reasons, we aimed to investigate any possible associations between psychological features, trauma, and inflammatory biomarkers with loneliness in people with ED. Methods: This study examined the interaction between loneliness, eating psychopathology, and biological markers in people with EDs. A group of 97 female patients with various diagnoses of ED was assessed for loneliness, general and eating psychopathology, t…
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Effects of nature-adapted lighting solutions ("Virtual Sky") on subjective and objective correlates of sleepiness, well-being, visual and cognitive performance at the workplace.
Exposure to natural daylight benefits human well-being, alertness, circadian rhythms and sleep. Many workplaces have limited or no access to daylight. Thus, we implemented a light-panel ("Virtual Sky"), which reproduced nature-adapted light scenarios. In a laboratory office environment, three lighting scenarios were presented during the day: two lighting conditions with nature-adapted spectral light distributions, one with static and one with dynamic clouds, and a standard office lighting condition. We compared the impact of the three lighting scenarios on subjective and objective measures of alertness, cognitive performance, wellbeing, visual comfort, contrast sensitivity, and cortisol levels in 18 healthy young male volunteers in a within-participant cross-over study design. We found no evidence that an 8-h lighting scenario with static or dynamic clouds during the waking day (9am-5pm)…
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Is paternal oxytocin an oxymoron? Oxytocin, vasopressin, testosterone, oestradiol and cortisol in emerging fatherhood.
How do hormonal levels in men change from pregnancy to after the birth of their firstborn child, and what is the role of oxytocin, alone or in interplay with other hormones, in explaining variance in their parenting quality? We explored in 73 first-time fathers the development of five hormones that have been suggested to play a role in parenting: oxytocin (OT), vasopressin (AVP), testosterone (T), oestradiol (E2) and cortisol (Cort). In an extended group of fathers (N = 152) we examined associations with fathers' behaviour with their 2-month-old infants. OT and E2 showed stability from the prenatal to the postnatal assessments, whereas AVP and T decreased significantly, and Cort decreased marginally. OT on its own or in interplay with other hormones was not related to paternal sensitivity. Using an exploratory approach, the interaction between T and E2 emerged as relevant for fathers' se…
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Impact of a Mindfulness-Based Stress Reduction Program on Psychological Well-Being, Cortisol, and Inflammation in Women Veterans.
Background: Women veterans experience higher levels of stress-related symptoms than their civilian counterparts. Psychological stress is associated with greater inflammation and may increase risk for cardiovascular disease (CVD). Mindfulness-based stress reduction (MBSR) has been found to improve psychological well-being in other populations but no randomized controlled trials (RCT) have been conducted examining the impact of MBSR on well-being and inflammation in women veterans at risk for CVD. Objective: Determine the effectiveness of MBSR in improving psychological well-being, cortisol, and inflammation associated with CVD in women veterans. Design: The design is a RCT comparing MBSR to an active control condition (ACC) consisting of a health education program. Participants: Women veterans (N=164) with risk factors for CVD from the Chicagoland area participated in the study. Intervent…
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Touch-Based Stressless Cortisol Sensing.
Tracking fluctuations of the cortisol level is important in understanding the body's endocrine response to stress stimuli. Traditional cortisol sensing relies on centralized laboratory settings, while wearable cortisol sensors are limited to slow and complex assays. Here, a touch-based non-invasive molecularly imprinted polymer (MIP) electrochemical sensor for rapid, simple, and reliable stress-free detection of sweat cortisol is described. The sensor readily measures fingertip sweat cortisol via highly selective binding to the cortisol-imprinted electropolymerized polypyrrole coating. The MIP network is embedded with Prussian blue redox probes that offer direct electrical signaling of the binding event to realize sensitive label-free amperometric detection. Using a highly permeable sweat-wicking porous hydrogel, instantaneously secreted fingertip sweat can be conveniently and rapidly co…
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Intravenous Infusion of Cortisol, Adrenaline, or Noradrenaline Alters Porcine Immune Cell Numbers and Promotes Innate over Adaptive Immune Functionality.
Despite the importance of pigs (Sus scrofa domestica) in livestock production and their increasing role as a model organism for human physiology, knowledge about the porcine immune system under the influence of stress hormones is fragmentary. Exceptionally little is known about the effects of catecholamines. Therefore, the aim of this study was to examine the in vivo effects of adrenaline, noradrenaline, and cortisol on number and functionality of porcine blood immune cells. Castrated male pigs (n = 34) were treated with physiological doses of either adrenaline, noradrenaline, or cortisol via i.v. infusion for 48 h. Blood samples were collected before treatment (-24 h, -22 h, 0 h), during treatment (+2 h, +24 h, +48 h), and at 72 h postinfusion. Immune cell numbers and phagocytic activity were evaluated by flow cytometry and lymphocyte proliferation by 3H-thymidine incorporation. Total I…
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Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat.
Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threa…
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Allostatic Load as a Biological Substrate to Intrinsic Capacity: A Secondary Analysis of CRELES.
Objectives: Intrinsic capacity (IC) is one of the latest views of positive aging. In its current status lacks a biological substrate amenable to be intervened. The aim of this study was to determine the association of allostatic load (AL) with IC. Design: We present a cross-sectional analysis of the Costa Rican Longevity and Healthy Aging Study. Setting: This report is from a representative sample of Costa Rican older adults; one of the countries that integrate the Central America region. Participants: 2,827, 60-year or older community-dwelling individuals. Methods: An IC index was gathered and validated, including different domains: cognitive, psychological, sensory, vitality and locomotion. AL was integrated with: blood pressure, abdominal obesity, body mass index, HDL-cholesterol, glycosylated hemoglobin, DHEAS, cortisol, epinephrine and norepinephrine. AL was grouped in three categor…
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Voluntary exercise reduces plasma cortisol levels and improves transitory memory impairment in young and aged Octodon degus.
Sleep deprivation (SD) has been reported to induce transient cognitive impairment in functional domains commonly affected in dementia, including memory. Indeed, sleep disturbance has been proposed as an early marker for Alzheimer's disease (AD). SD emulates many aging-related modifications, including important memory dysfunctions possibly caused by triggers of stress such as cortisol. Although exercise is widely assumed to be beneficial for overall health, only recently has the research community focused its attention on its possible effects on brain functions such as cognition. Octodon degus (O. degus) is a recent rodent model considered suitable for the study of neurodegenerative diseases, since it spontaneously develops several histopathological hallmarks observed in AD. We aimed to uncover the interaction between stress, exercise, age and transient memory impairments after SD insult.…
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Heart Rate Variability, Cortisol and Attention Focus During Shamatha Quiescence Meditation.
Cardiac vagal tone can be seen as a stable marker for the ability to sustain attention and regulate emotion, two factors associated with the quality of meditation. In this study, heart rate variability (HRV) has been monitored in different forms of Shamatha quiescence meditation: three breath meditations, Settling the Mind in its natural state, Awareness of Awareness, Loving-kindness and Tonglen. Establish and test a practical means of monitoring neurobiological effects of meditation. Over 6 weeks, two experimental groups practiced Shamatha meditation on a daily basis (n = 20). HRV patterns and cortisol tests were monitored at three measuring points during these weeks, and an attention focus test was performed at the start and after 6 weeks. Six weeks of regular practice in Shamatha meditation were associated with HRV indices suggesting improvements in the homeostatic regulation of the a…
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Association between internet gaming addiction and leukocyte telomere length in Korean male adolescents.
Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth. In particular, the potential association between IGA and leukocyte telomere length (LTL) has yet to be examined. In this study we compared LTL in Korean male adolescents with and without IGA and examined the association between LTL and autonomic functions. Specifically, plasma catecholamine, serum cortisol, and psychological stress levels were measured as autonomic functions. Data were collected using participant blood samples analyzed for LTL, catecholamine, and cortisol levels and a set of questionnaires to assess IGA and psychological stress levels of the participants. The LTL measurements were made using a qPCR-based technique, and the relative LTL was calculated as the telomere/single copy (T/S) ratio. T/S ratio was significantly shorter in the IGA group than in the non-IGA …
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Acute cortisol response to a psychosocial stressor is associated with heartbeat perception.
The aim of the present study was to examine the effect of an acute increase in cortisol in response to a psychosocial stressor on heartbeat perception, in a laboratory environment. Thirty-six participants (20 women, 16 men, mean age = 21.7 years, standard deviation = 1.7 years) completed a heartbeat counting task (Schandry paradigm) before and after exposure to an acute psychosocial stressor (Trier Social Stress Test; TSST). Heartbeat counting performance was compared between participants who exhibited strong cortisol responses (>15.5% increase in cortisol from baseline; responders) and those who did not (non-responders). Responders showed increased heartbeat counting accuracy following the TSST, which was not observed in non-responders. The two groups did not differ in their responsivity to subjective anxiety ratings or heart rate. These results indicated that acutely elevated cortisol …
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