HPA axis and cortisol

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

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

Marital satisfaction, recovery from work, and diurnal cortisol among men and women.

Design: Multilevel modeling was used to model relationships between salivary cortisol, daily diary ratings of work experiences, and Marital Adjustment Test scores (Locke & Wallace, 1959), in a sample of 60 adults who sampled saliva 4 times per day over 3 days. Results: Among women but not men, marital satisfaction was significantly associated with a stronger basal cortisol cycle, with higher morning values and a steeper decline across the day. For women but not men, marital satisfaction moderated the within-subjects association between afternoon and evening cortisol level, such that marital quality appeared to bolster women's physiological recovery from work. For both men and women, evening cortisol was lower than usual on higher-workload days, and marital satisfaction augmented this association among women. Men showed higher evening cortisol after more distressing social experiences at …

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Associations of salivary cortisol with cognitive function in the Baltimore memory study.

Context: The stress responses of the hypothalamic-pituitary-adrenal axis can produce adverse effects on the brain. Previous studies have concluded that an elevated level of cortisol is a risk factor for cognitive dysfunction and decline in aging but have been limited by sex exclusion, restricted cognitive batteries, and small sample sizes. Objective: To examine associations among salivary cortisol metrics and cognitive domain scores in an urban adult population. Design, setting, and participants: A cross-sectional analysis was conducted using data from a longitudinal study involving 1140 Baltimore, Maryland, residents aged 50 to 70 years. Four salivary cortisol samples were obtained from 967 participants across 1 study visit (before, during, and after cognitive testing as well as at the end of the visit) from which 7 cortisol metrics were created. We examined associations of cortisol met…

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A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness.

Context: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes. Objective: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation. Design: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger's test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V. Results: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P …

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Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology-A global perspective.

There is clear evidence that the mother's stress, anxiety, or depression during pregnancy can alter the development of her fetus and her child, with an increased risk for later psychopathology. We are starting to understand some of the underlying mechanisms including the role of the placenta, gene-environment interactions, epigenetics, and specific systems including the hypothalamic-pituitary-adrenal axis and cytokines. In this review we also consider how these effects may be different, and potentially exacerbated, in different parts of the world. There can be many reasons for elevated prenatal stress, as in communities at war. There may be raised pregnancy-specific anxiety with high levels of maternal and infant death. There can be raised interpersonal violence (in Afghanistan 90.2% of women thought that "wife beating" was justified compared with 2.0% in Argentina). There may be interac…

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Reciprocal affiliation among adolescent rats during a mild group stressor predicts mammary tumors and lifespan.

Objective: Although the detrimental physical health effects of social isolation have been known for three decades, the answers to how and why social relationships generally improve health remain elusive. Social relationships are not always beneficial, and we examined a structural dimension that may bring about their salubrious effects: affiliative reciprocity during a stressor. Methods: In a lifespan study, female rats lived with their sisters and were tested for temperament, affiliative reciprocity during an everyday stressor at puberty, corticosterone response to a stressor, mammary tumor development and diagnosis, and death. Results: Rats that affiliated more reciprocally during a mild group stressor survived longer (p = .0005), having exhibited a lower corticosterone peak in response to an acute novel stressor in late adulthood (p = .0015), and longer time to the development of spont…

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Reduced cortisol metabolism during critical illness.

Background: Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. Methods: In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. Results: Total and free circulating cortisol levels were consistently higher in the patients …

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Cortisol reactivity to social stress in adolescents: role of depression severity and child maltreatment.

This study examined the hypothesis that depressed adolescents with a history of childhood maltreatment will show greater cortisol reactivity to psychological stress challenge than those without, and this relation will be moderated by level of depression severity. Seventy-one adolescents were exposed to the Trier Social Stress Test. Salivary cortisol was assessed at baseline, immediately before the challenge, after the challenge, and during an extended recovery period. Childhood maltreatment was assessed with a rigorous contextual interview and rating system. Adolescents with a history of maltreatment produced higher and more prolonged levels of cortisol in response to the challenge than did adolescents with no maltreatment, but only among those with a mild/moderate level of depression severity. Those with moderate/severe depression exhibited a blunted cortisol response regardless of chil…

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Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans.

Background: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between testosterone and aggression remains correlational and inconclusive. Methods: Twelve female participants underwent functional magnetic resonance imaging during three sessions while viewing stimuli differing in social threat value: angry and happy facial expressions. The first session served to establish associations between baseline hormone levels and neural activation. Participants were retested in a second and third session after placebo-controlled sublingual administration of .5 mg testosterone. Results: Findings demonstrate consistent activation to angry versus happy faces in areas known to be invol…

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Daily hassles and eating behaviour: the role of cortisol reactivity status.

Previous research has shown high cortisol reactors to consume a greater amount of snack foods than low reactors following a laboratory stressor. The current study tested whether high cortisol reactors also consume more snacks than low reactors in response to field stressors. Fifty pre-menopausal women completed a laboratory stressor, provided saliva samples to assess cortisol reactor status and then completed daily hassles and snack intake diaries over the next fourteen days. Hierarchical multivariate linear modelling showed a significant association between daily hassles and snack intake within the overall sample, where an increased number of hassles was associated with increased snack intake. This significant positive association between number of hassles and snack intake was only observed within the high cortisol reactors and not within the low cortisol reactors. These findings sugges…

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Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress.

Background: Ghrelin plays important roles in glucose metabolism, appetite, and body weight regulation, and recent evidence suggests ghrelin prevents excessive anxiety under conditions of chronic stress. Methods: We used ghrelin knockout (ghr-/-) mice to examine the role of endogenous ghrelin in anxious behavior and hypothalamic-pituitary-adrenal axis (HPA) responses to acute stress. Results: Ghr-/- mice are more anxious after acute restraint stress, compared with wild-type (WT) mice, with three independent behavioral tests. Acute restraint stress exacerbated neuronal activation in the hypothalamic paraventricular nucleus and medial nucleus of the amygdala in ghr-/- mice compared with WT, and exogenous ghrelin reversed this effect. Acute stress increased neuronal activation in the centrally projecting Edinger-Westphal nucleus in WT but not ghr-/- mice. Ghr-/- mice exhibited a lower cortic…

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Adult hippocampal neurogenesis buffers stress responses and depressive behaviour.

Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness. In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis. Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking. Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mi…

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Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus.

Numerous studies have established a link between individuals with affective disorders and a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, most notably characterized by a reduced sensitivity to glucocorticoid negative (-) feedback. Furthermore there is a sex difference in the etiology of mood disorders with incidence in females being two to three times that of males, an association that may be a result of the influence of estradiol (E2) on HPA axis function. In these studies, we have examined the effect of E2 on glucocorticoid-mediated HPA axis (-) feedback during both the diurnal peak and the stress-induced rise in corticosterone (CORT). Young adult female Sprague-Dawley (SD) rats were ovariectomized (OVX) and 1 week later treated subcutaneous (s.c.) with oil or estradiol benzoate (EB) for 4 days. On the 4th day of treatment, animals were injected with a single dose of …

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Psychophysiological Effects of Dance Movement Therapy and Physical Exercise on Older Adults With Mild Dementia: A Randomized Controlled Trial.

Objectives: Dementia interferes with older adults' functioning in cognitive, daily, psychosocial, and neuroendocrine domains. The present study examined the psychophysiological effects of dance movement therapy (DMT) and physical exercise for older adults with dementia. Methods: This randomized controlled trial recruited 204 older adults diagnosed with mild dementia into the DMT, exercise, or waitlist control group. Both DMT and exercise interventions had similar intensity and comprised 24 hr of intervention that spanned over 12 weeks. All participants completed self-report questionnaires on psychosocial well-being, daily functioning, neurocognitive assessments, and salivary cortisol measures at baseline and 3 follow-up measurements more than 1 year. Results: The DMT group showed significant decreases in depression, loneliness, and negative mood (d = 0.33-0.42, p < .05) and improved dail…

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Acceptance and Commitment Therapy Reduces Psychological Stress in Patients With Inflammatory Bowel Diseases.

Background & aims: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD). Methods: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20…

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An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.

Background: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. Methods: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. Results: All participants completed the trial…

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Fostering Resilience among Mothers under Stress: "Authentic Connections Groups" for Medical Professionals.

Background: We report on effects of an intervention to foster resilience among professional women at high risk for stress and burnout: health care providers (physicians, PhD clinicians, physician assistants, and nurse practitioners) who are mothers. Methods: Between February and November 2015, 40 mothers on staff at the Mayo Clinic, Arizona, were assigned randomly to either 1) 12 weekly 1-hour sessions of a structured, relational supportive intervention, the Authentic Connections Groups (n = 21) with protected time to attend sessions or to 2) 12 weekly hours of protected time to be used as desired (controls; n = 19). Participants were assessed at baseline, after the intervention, and 3 months follow-up on multiple psychological measures plus plasma cortisol. Results: Across the 12 weeks of the intervention groups, there were zero dropouts. After the intervention, analyses of covariance s…

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Particulate Matter Exposure and Stress Hormone Levels: A Randomized, Double-Blind, Crossover Trial of Air Purification.

Background: Exposure to ambient particulate matter (PM) is associated with a number of adverse health outcomes, but potential mechanisms are largely unknown. Metabolomics represents a powerful approach to study global metabolic changes in response to environmental exposures. We therefore conducted this study to investigate changes in serum metabolites in response to the reduction of PM exposure among healthy college students. Methods: We conducted a randomized, double-blind crossover trial in 55 healthy college students in Shanghai, China. Real and sham air purifiers were placed in participants' dormitories in random order for 9 days with a 12-day washout period. Serum metabolites were quantified by using gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-mass spectrometry. Between-treatment differences in metabolites were examined using orthogonal parti…

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Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.

The emerging concept of psychobiotics-live microorganisms with a potential mental health benefit-represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxi…

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The impact of a brief gratitude intervention on subjective well-being, biology and sleep.

This randomised controlled experiment tested whether a brief subjective well-being intervention would have favourable effects on cardiovascular and neuroendocrine function and on sleep. We compared 2 weeks of a gratitude intervention with an active control (everyday events reporting) and no treatment conditions in 119 young women. The treatment elicited increases in hedonic well-being, optimism and sleep quality along with decreases in diastolic blood pressure. Improvements in subjective well-being were correlated with increased sleep quality and reductions in blood pressure, but there were no relationships with cortisol. This brief intervention suggests that subjective well-being may contribute towards lower morbidity and mortality through healthier biological function and restorative health behaviours.

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The effects of a multi-component dyadic intervention on the psychological distress of family caregivers providing care to people with dementia: a randomized controlled trial.

Background: Earlier research showed that multi-component dyadic interventions - including a combination of intervention strategies and addressing both the person with dementia and caregiver - have a beneficial impact on the mental and physical health of people with dementia and their family caregivers. A randomized controlled trial (RCT) of a multi-component dyadic intervention, which is a translated and adapted version of an intervention that has been shown to be effective in the US by Teri et al. (2003), was performed. The effects on caregivers' mood (primary outcome), burden, general health, and salivary cortisol levels (secondary outcomes) were studied. Methods: Community-dwelling people with dementia and their family caregivers (N = 111 dyads) were randomly assigned. The experimental group received eight home visits during three months, combining physical exercise and support (psych…

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Mindfulness-based cancer recovery and supportive-expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors.

Background: Group psychosocial interventions including mindfulness-based cancer recovery (MBCR) and supportive-expressive group therapy (SET) can help breast cancer survivors decrease distress and influence cortisol levels. Although telomere length (TL) has been associated with breast cancer prognosis, the impact of these two interventions on TL has not been studied to date. Methods: The objective of the current study was to compare the effects of MBCR and SET with a minimal intervention control condition (a 1-day stress management seminar) on TL in distressed breast cancer survivors in a randomized controlled trial. MBCR focused on training in mindfulness meditation and gentle Hatha yoga whereas SET focused on emotional expression and group support. The primary outcome measure was relative TL, the telomere/single-copy gene ratio, assessed before and after each intervention. Secondary ou…

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Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: Randomized trial showing improved treatment retention and outcome.

Background: Prolonged exposure (PE) therapy for post-traumatic stress disorder (PTSD) in military veterans has established efficacy, but is ineffective for a substantial number of patients. PE is also associated with high dropout rates. We hypothesized that hydrocortisone augmentation would enhance symptom improvement and reduce drop-out rates by diminishing the distressing effects of traumatic memories retrieved during imaginal exposure. We also hypothesized that in responders, hydrocortisone augmentation would be more effective in reversing glucocorticoid indices associated with PTSD than placebo augmentation. Method: Twenty-four veterans were randomized to receive either 30 mg oral hydrocortisone or placebo prior to PE sessions 3-10 in a double-blind protocol. Glucocorticoid receptor sensitivity was assessed in cultured peripheral blood mononuclear cells (PBMC) using the in vitro lyso…

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Effects of antenatal yoga on maternal anxiety and depression: a randomized controlled trial.

Background: Antenatal depression and anxiety are associated with adverse obstetric and mental health outcomes, yet practicable nonpharmacological therapies, particularly for the latter, are lacking. Yoga incorporates relaxation and breathing techniques with postures that can be customized for pregnant women. This study tested the efficacy of yoga as an intervention for reducing maternal anxiety during pregnancy. Methods: Fifty-nine primiparous, low-risk pregnant women completed questionnaires assessing state (State Trait Anxiety Inventory; STAI-State), trait (STAI-Trait), and pregnancy-specific anxiety (Wijma Delivery Expectancy Questionnaire; WDEQ) and depression (Edinburgh Postnatal Depression Scale; EPDS) before randomization (baseline) to either an 8-week course of antenatal yoga or treatment-as-usual (TAU); both groups repeated the questionnaires at follow-up. The yoga group also co…

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Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.

Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life stress. We carried out an experimental comparison of 140 men and women aged 50-75 y with type 2 diabetes and 280 nondiabetic individuals matched on age, sex, and income. We monitored blood pressure (BP) and heart rate, salivary cortisol, plasma interleukin (IL)-6, and total cholesterol in response to standardized mental stress, and assessed salivary cortisol over the day. People with type 2 diabetes…

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Personality trait predictors of placebo analgesia and neurobiological correlates.

Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here, we assessed psychological traits in 50 healthy controls as to their capacity to predict placebo analgesic effects, placebo-induced activation of μ-opioid neurotransmission and changes in cortisol plasma levels during a sustained experimental pain challenge (hypertonic saline infused in the masseter muscle) with and without placebo administration. Statistical analyses showed that an aggregate of scores from Ego-Resiliency, NEO Altruism, NEO Straightforwardness (positive predictors) and NEO Angry Hostility (negative predictor) scales accounted for 25% of the variance in placebo analgesic responses. Molecular imaging showed that subjects scoring above the median in a composite of those …

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