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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126 to 150 of 897Enhanced cortisol response to stress in children in autism.
Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a novel environment; and (3) in response to a blood draw stressor. A significantly higher serum cortisol response was found in the group of children with autism. Analysis showed significantly higher peak cortisol levels and prolonged duration and recovery of cortisol elevation following the blood-stick stressor in children with autism. This study suggests increased reactivity of the HPA axis to stress and novel stimuli in children with autism.
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Timing matters: long term effects of adversities from prenatal period up to adolescence on adolescents' cortisol stress response. The TRAILS study.
Objective: Altered cortisol response is a vulnerability marker for a variety of stress-related diseases and psychiatric disorders. Childhood adversity has been shown to modify this response, but evidence is inconsistent. Effects may differ depending on the timing of exposure, or due to the interplay between pre/postnatal adversity and later adversities. The present study examined the influence of adversity during different timeframes (pre/postnatal, ages 0-5, 6-11, 12-13, 14-15 years), and the interaction between pre/postnatal and later adversity on adolescents' cortisol stress response. Method: Four salivary cortisol samples were collected before and after a social stress test in 471 16-year-old adolescents from the longitudinal study TRAILS. Data on pre/postnatal exposure to adversities were obtained from Preventive Child Healthcare records and parental reports, subsequent adversities …
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Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes.
Context: Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. Objectives: To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Design: Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-d…
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Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?
Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results furth…
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Hypocortisolism as a potential marker of allostatic load in children: associations with family risk and internalizing disorders.
Although the majority of research attention to the hypothalamic-pituitary-adrenal (HPA) axis in stress-related disorders and as a marker of allostatic load has focused on overactivation of this stress system, theory and data clearly indicate that underactivation is also an important type of dysregulation. In the current study we focused on low cortisol, exploring a constellation of risk factors including stress exposure, maternal depression, and attenuated basal and stress reactive cortisol in two samples of children. The first sample was comprised of 110 preschoolers living in high-stress environments. Cortisol was assessed across the day at home and at child care as well as across two stress paradigms. These data were used to classify whether children's HPA axis activity was attenuated. Serious family financial strain, maternal depression, and attenuated cortisol all made unique contri…
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Elevated macrophage migration inhibitory factor (MIF) is associated with depressive symptoms, blunted cortisol reactivity to acute stress, and lowered morning cortisol.
Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine produced by leukocytes and the secretory cells of the HPA axis. Remarkably, glucocorticoids (GC) induce leukocyte MIF secretion, while MIF renders leukocytes insensitive to the anti-inflammatory effects of glucocorticoids. In light of reported associations between dysphoric states, increased inflammatory activity, and reduced GC sensitivity, the current study investigated the association between MIF, loneliness and depressive symptoms. The study further investigated the relation between plasma MIF and markers of HPA function, i.e., diurnal cortisol and the cortisol response to acute stress. Healthy university undergraduates (N=126; 64 women) were invited to participate if their scores on the Beck Depression Inventory or UCLA loneliness scale were in the upper or lower quintile of their peer group. Plasma MIF and s…
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BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions.
Background: A key protein in maintaining neuronal integrity throughout the life span is brain-derived neurotrophic factor (BDNF). The BDNF gene is characterized by a functional polymorphism, which has been associated with stress-related disorders such as anxiety-related syndromes and depression, prompting us to examine individual responses by Genotype and Sex to a standardized social stress paradigm. Gender differences in BDNFxstress responses were posited because estrogen induces synthesis of BDNF in several brain regions. Methods: 97 university students (51 females and 46 males) participated in a social stress procedure (Trier Social Stress Test, TSST). Indices of stress were derived from repeated measurement of cortisol, blood pressure, and heart rate during the TSST. All subjects were genotyped for the Val66Met polymorphism. Results: Tests of within-subject effects showed a significa…
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Gene-environment interactions predict cortisol responses after acute stress: implications for the etiology of depression.
Background: Growing evidence suggests that the serotonin transporter polymorphism (5-HTTLPR) interacts with adverse environmental influences to produce an increased risk for the development of depression while the underlying mechanisms of this association remain largely unexplored. As one potential intermediate phenotype, we investigated alterations of hypothalamic-pituitary-adrenal (HPA) axis responses to stress in individuals with no history of psychopathology depending on both 5-HTTLPR and stressful life events. Methods: Healthy male adults (N=100) were genotyped and completed a questionnaire on severe stressful life events (Life Events Checklist). To test for gene-by-environment interactions on endocrine stress reactivity, subjects were exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol levels were obtained at 6 time points prior to the stressor and d…
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Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome.
Background & aims: A history of early adverse life events (EALs) is associated with a poorer outcome and higher levels of distress in adult patients with functional gastrointestinal disorders. An EAL is thought to predispose individuals to develop a range of chronic illnesses by inducing persistent changes in the central stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. We sought to determine if EALs affect the HPA axis response to a visceral stressor in irritable bowel syndrome (IBS) patients and healthy controls, and to determine if this is affected by sex or related to symptoms or quality of life. Methods: Forty-four IBS patients (25 women, 19 men) and 39 healthy controls (21 women, 18 men) were assessed for gastrointestinal and psychological symptoms and EALs by validated questionnaires and interview. All subjects underwent a visceral stressor (sigmoid…
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Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome.
Enhanced stress responsiveness has been implicated as a potential mechanism contributing to the pathophysiology of irritable bowel syndrome (IBS), and should be reflected in altered function of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Both of these systems can modulate mucosal immune function. The aims of this study were: (i) to characterize the basal circadian rhythm of adrenocorticotropin hormone (ACTH) and cortisol in IBS vs healthy controls; (ii) to compare stimulated ACTH, cortisol and noradrenaline responses to a pelvic visceral stressor (sigmoidoscopy) in IBS and controls; and (iii) to correlate neuroendocrine responses with colonic mucosal cytokine expression and symptoms in IBS. Two separate studies were conducted in women. In Study 1, basal cortisol levels were analysed in 41 IBS and 25 controls using 24-h collections of plasma ACTH and …
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Exercise and circulating cortisol levels: the intensity threshold effect.
This study examined the influence of exercise intensity upon the cortisol response of the hypothalamic-pituitary-adrenal (HPA) axis. Specifically, we examined exercise at intensities of 40, 60, and 80% maximal oxygen uptake (VO2max) in an attempt to determine the intensity necessary to provoke an increase in circulating cortisol. Twelve active moderately trained men performed 30 min of exercise at intensities of 40, 60, and 80% of their VO2max, as well as a 30-min resting-control session involving no exercise on separate days. Confounding factors such as time of day--circadian rhythms, prior diet--activity patterns, psychological stress, and levels of exercise training were controlled. Cortisol and ACTH were assessed in blood collected immediately before (pre-) and after (post-) each experimental session. Statistical analysis involved repeated measures analysis of variance and Tukey post…
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Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor.
The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-indu…
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Rejection sensitivity relates to hypocortisolism and depressed mood state in young women.
Rejection sensitivity and the associated fear of negative social evaluation (FNSE) trait are characteristics of hypocortisolemic syndromes such as atypical depression. However, a meta-analysis showed that acute FNSE evokes strong cortisol responses in humans. This is consistent with suggestions that hypocortisolism reflects a protective adaptation to a history of high cortisol responses. This leads us to hypothesize that measures of trait FNSE relate to hypocortisolism. Moreover, because FNSE relates positively to depressed mood state, but negatively to cortisol, we expect that the positive relationship between depressed mood state and cortisol will show up most clearly when controlling for the confounding effect of FNSE on this relationship. In the present study we measured salivary cortisol awakening response and psychological variables in 194 community women aged 18-30 years. The resu…
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Chronic stress exacerbates tau pathology, neurodegeneration, and cognitive performance through a corticotropin-releasing factor receptor-dependent mechanism in a transgenic mouse model of tauopathy.
Because overactivation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in Alzheimer's disease (AD), dysregulation of stress neuromediators may play a mechanistic role in the pathophysiology of AD. However, the effects of stress on tau phosphorylation are poorly understood, and the relationship between corticosterone and corticotropin-releasing factor (CRF) on both β-amyloid (Aβ) and tau pathology remain unclear. Therefore, we first established a model of chronic stress, which exacerbates Aβ accumulation in Tg2576 mice and then extended this stress paradigm to a tau transgenic mouse model with the P301S mutation (PS19) that displays tau hyperphosphorylation, insoluble tau inclusions and neurodegeneration. We show for the first time that both Tg2576 and PS19 mice demonstrate a heightened HPA stress profile in the unstressed state. In Tg2576 mice, 1 month of restraint/isolation (RI)…
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[Cytokines in psychoneuroendocrine immunological context of nonspecific musculoskeletal pain].
Cytokines are coordinators of immune homeostasis. Evidence for the participation of cytokines in neurogenic inflammation, peripheral and central sensitization and hyperalgesia as well as for induction of inflammatory immune responses by pain-related catastrophizing is well documented. A disproportion of proinflammatory and anti-inflammatory cytokines is known to be a contributory cause of pain and pain behavior. Embedded into psychoneuroendocrine immunological feedback control systems cytokines are able to perpetuate a virtuous circle between local inflammation and systemic pain behavior (pain/sickness behavior) thus contributing to chronification of nonspecific musculoskeletal pain. In this model avoidance and pain-related nonrecognition as key components of systemic pain behavior lead to maintenance of the virtuous circle by generating of a local inflammation with local and systemic co…
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Depression gets old fast: do stress and depression accelerate cell aging?
Depression has been likened to a state of "accelerated aging," and depressed individuals have a higher incidence of various diseases of aging, such as cardiovascular and cerebrovascular diseases, metabolic syndrome, and dementia. Chronic exposure to certain interlinked biochemical pathways that mediate stress-related depression may contribute to "accelerated aging," cell damage, and certain comorbid medical illnesses. Biochemical mediators explored in this theoretical review include the hypothalamic-pituitary-adrenal axis (e.g., hyper- or hypoactivation of glucocorticoid receptors), neurosteroids, such as dehydroepiandrosterone and allopregnanolone, brain-derived neurotrophic factor, excitotoxicity, oxidative and inflammatory stress, and disturbances of the telomere/telomerase maintenance system. A better appreciation of the role of these mediators in depressive illness could lead to ref…
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Resilience: research evidence and conceptual considerations for posttraumatic stress disorder.
The growing recognition and occurrence of traumatic exposure in the general population has given increased salience to the need to understand the concept of resilience. More than just the "flip side" of a risk factor, the notion of resilience encompasses psychological and biological characteristics, intrinsic to an individual, that might be modifiable and that confer protection against the development of psychopathology in the face of stress. In this review, we provide some perspective on the concept of "resilience" by examining early use of the term in research on "children at risk" and discuss the relationship between risk and resilience factors. We then review psychological and biological factors that may confer resilience to the development of posttraumatic stress disorder (PTSD) following trauma, examine how resilience has been assessed and measured, and discuss issues to be address…
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Stress, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, and aggression.
This comprehensive review explores the intricate relationship between the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and aggression. It provides a detailed overview of the physiology and functioning of these axes, as well as the implications for aggressive behavior. The HPA axis, responsible for the stress response, is activated in response to various stressors and can influence aggressive behavior. Glucocorticoids, such as cortisol, play a crucial role in stress-induced activation of the HPA axis and have been implicated in aggressive tendencies. Chronic stress can dysregulate the HPA axis, leading to alterations in cortisol levels and potentially contributing to aggressive behavior. The HPG axis, particularly the androgen hormone testosterone, is also closely linked to aggression. Animal and human studies have consistently shown a positive…
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Assisting couples to develop healthy relationships: effects of couples relationship education on cortisol.
Introduction: Couple conflict in unhappy marriages is suggested to impair individual health via chronic psychophysiological stress reactions in couples' everyday lives. As a consequence, we hypothesized that standard couples relationship education (CRE) would decrease psychophysiological stress, namely salivary cortisol levels, during couple conflict in the laboratory as compared to a standard psychological stress paradigm. We considered cortisol to be of particular interest in this context, as it mediates endocrine and immune responses to stress, and thus might influence couples' health. Methods: Salivary cortisol was repeatedly investigated in 61 couples during (a) a standard psychological stress test with no relevance for the couples, and (b) a standard couple conflict discussion in the laboratory before and after CRE. In addition, increases in self-evaluated relationship quality were…
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Effect of service dogs on salivary cortisol secretion in autistic children.
Children with Autism Syndrome Disorders (ASDs) exhibit social, communicative, and behavioral deficits. We know that human interaction with dogs, which is thought to serve as a social catalyst, results in a decrease of cortisol levels in healthy adults. Introducing service dogs to children with ASD is an attractive idea that has received growing attention in recent decades. However, no study has measured the physiological impact of service dogs on these children. Therefore, the goal of our study was to assess the effects of service dogs on the basal salivary cortisol secretion of children with ASD. We measured the salivary cortisol levels of 42 children with ASD in three experimental conditions; prior to and during the introduction of a service dog to their family, and after a short period during which the dog was removed from their family. We compared average cortisol levels and Cortisol…
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Glucocorticoids enhance in vivo exposure-based therapy of spider phobia.
Background: Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes. In particular, it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights. Here, we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia. Methods: In a double blind, block-randomized, placebo-controlled, between-subject study design, 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy. Cortisol (20 mg) or placebo was orally administered 1 hr before each therapy session. Patients returned for a follow-up assessment one month after therapy. Results: Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire (FSQ) from pre…
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Maternal plasma levels of oxytocin during breastfeeding-A systematic review.
Introduction: Oxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available. Materials and methods: Systematic literature searches on breastfeeding induced oxytocin levels were conducted 2017 and 2019 in PubMed, Scopus, CINAHL, and PsycINFO. Data on oxytocin linked effects and effects of medical interventions were included if available. Results: We found 29 articles that met the inclusion criteria. All studies had an exploratory design and included 601 women. Data were extracted from the articles and summarised in tables. Breastfeeding induced an immediate and short lasting (20 minutes) release of oxytocin. The release was pulsatile early postpartum (5 pulses/10 minutes) and coalesced into a more protracted rise as lactation proceeded. Oxytocin levels were higher in multiparous versus primiparous women. The number of o…
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Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder.
Treatment studies have suggested that omega-3 fatty acids (omega-3 FAs) as monotherapy or adjunctive treatment have therapeutic effects in depression. The authors recently reported a study in which fluoxetine and eicosapentaenoic acid (EPA), which is an omega-3 fatty acid, appeared to be equally effective in controlling depressive symptoms and their combination was superior to either of them alone. Regulation of hypothalamus-pituitary-adrenal (HPA) axis activity and reduction of inflammatory cytokines are among several biological mechanisms which potentially explain the impact of omega-3 FAs on depression. In the present study, plasma cortisol and serum interleukin-1beta (IL-1 beta) and interleukin-6 (Il-6) were measured in patients with a diagnosis of major depressive disorder (MDD) participating in aforementioned trial to determine the effects of 8 weeks of treatment of depression with…
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Cultures under stress: A cross-national meta-analysis of cortisol responses to the Trier Social Stress Test and their association with anxiety-related value orientations and internalizing mental disorders.
Acute cortisol changes are physiological indicators (i.e., biomarkers) of psychosocial stress that have been repeatedly assessed using standardized laboratory protocols like the Trier Social Stress Test (TSST). Despite this methodological standardization, however, cortisol stress responses vary considerably across different studies. Based on multilevel meta-analyses of 237 TSST studies (n = 8487 individuals), we demonstrate that ∼25% of this variability is actually attributable to systematic differences between countries. Particularly North American and European studies show a remarkable effect disparity (d = 0.45 vs. d = 0.73, respectively). Specifically, in-depth analyses suggested that the cultural orientation towards anxiety-related values in English-speaking countries (incl. the UK and Ireland) was associated with decreased cortisol stress responses. This finding was further support…
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Salivary alpha amylase-cortisol asymmetry in maltreated youth.
Background: Maltreatment represents a major stressor in the lives of many youth. Given the known effects of stress exposure on subsequent functioning of biological stress response systems, researchers have been interested in the effects of maltreatment on the functioning of these systems. Experimental studies reveal that previous exposure to stress affects the symmetry between components of the physiological stress response to subsequent stress. The present study examined asymmetry between salivary alpha amylase (sAA), a sympathetic indicator, and cortisol reactivity to a social stressor among maltreated and comparison youth age 9 to 14 years. Consistent with earlier studies suggesting that stress leads to asymmetry between hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity, we expected that maltreated youth would exhibit greater sAA-cortisol asymmetry than would…
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