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

The effects of stress and coping on surgical performance during simulations.

Objective: This study investigates the effects of surgeons' stress levels and coping strategies on surgical performance during simulated operations. Methods: Thirty surgeons carried out each a non-crisis and a crisis scenario of a simulated operation. Surgeons' stress levels were assessed by several measures: self-assessments and observer ratings of stress, heart rate, heart rate variability, and salivary cortisol. Coping strategies were explored qualitatively and quantified to a coping score. Experience in surgery was included as an additional predictor. Outcome measures consisted of technical surgical skills using Objective Structured Assessment of Technical Skill (OSATS), nontechnical surgical skills using Observational Teamwork Assessment for Surgery (OTAS), and the quality of the operative end product using End Product Assessment (EPA). Uni- and multivariate linear regression were u…

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Depression and anxiety: Associations with biological and perceived stress reactivity to a psychological stress protocol in a middle-aged population.

Background: Depression and anxiety have been linked to higher as well as lower reactivity to stressful circumstances. Large, population-based studies investigating the association between depression and anxiety, perceived and physiological stress responses are lacking. Methods: We studied 725 men and women, aged 55-60 years, from a population-based cohort, who filled out the Hospital Anxiety and Depression Scale (HADS). We performed a standardized interview on medical history and lifestyle. We measured continuous blood pressure (BP) and heart rate (HR) reactivity, saliva cortisol reactivity and perceived stress during a psychological stress protocol. Results: Albeit not statistically significant in all groups, systolic BP (SBP), diastolic BP (DBP), HR and cortisol reactivity to the psychological stress protocol were lower in those with mild-to-severe depression or anxiety symptoms and th…

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Dynamics of telomerase activity in response to acute psychological stress.

Telomerase activity plays an essential role in cell survival, by lengthening telomeres and promoting cell growth and longevity. It is now possible to quantify the low levels of telomerase activity in human leukocytes. Low basal telomerase activity has been related to chronic stress in people and to chronic glucocorticoid exposure in vitro. Here we test whether leukocyte telomerase activity changes under acute psychological stress. We exposed 44 elderly women, including 22 high stress dementia caregivers and 22 matched low stress controls, to a brief laboratory psychological stressor, while examining changes in telomerase activity of peripheral blood mononuclear cells (PBMCs). At baseline, caregivers had lower telomerase activity levels than controls, but during stress telomerase activity increased similarly in both groups. Across the entire sample, subsequent telomerase activity increase…

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Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD.

Rationale: Early Life Stress (ELS) increases risk for both adult traumatization and posttraumatic stress disorder (PTSD). Adult PTSD may also reflect a continuation of a response to an earlier exposure to adversity. Given similarities between neuroendocrine aspects of PTSD and ELS, such as in reduced cortisol signaling and glucocorticoid receptor (GR) responsiveness, some aspects of the biology of PTSD may reflect biological correlates of risk. Objectives: This paper will examine how empirical findings regarding the biological basis of ELS can inform our understanding of the neuroendocrinology of PTSD. This paper will also propose a hypothetical model to guide future research that integrates genetic, epigenetic, neuroendocrine, and psychological observations to understand the contribution of ELS neurobiology to PTSD. Results: Recent genetic findings demonstrate heritable aspects of at le…

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Neuroendocrine and psychometric evaluation of a placebo version of the 'Trier Social Stress Test'.

The "Trier Social Stress Test" (TSST) is one of the most prominent laboratory stress paradigms. It is often used to investigate the effects of stress on cognitive or affective parameters. Such studies need a non-stress control condition. However, control conditions currently employed are often rather ill defined and do not parallel important modulating variables, e.g., physical or cognitive load of the TSST. We here introduce a placebo version of the TSST, which contains a free speech and a simple mental arithmetic task without uncontrollability and social-evaluative threat. In two studies, this control condition was evaluated using salivary markers of stress reactivity (cortisol and alpha-amylase) and a questionnaire for anticipatory cognitive stress appraisal (PASA). In experiment 1 participants who were treated with the placebo condition showed no cortisol response and a small, but si…

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Rumination, distraction and mindful self-focus: effects on mood, dysfunctional attitudes and cortisol stress response.

Background: Although aggravating effects of rumination on dysfunctional cognitions and endocrine stress responses have been proposed, experimental studies testing these assumptions are lacking. In parallel, mindfulness theory suggests beneficial effects of mindfulness on dysfunctional cognitions. This study aimed to investigate the effects of induced rumination, distraction and mindful self-focus on mood and dysfunctional attitudes and to assess the possible impact of induced rumination on participants' cortisol responses. Method: Sixty university students were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction or mindful self-focus condition. The latter included statements focusing on self-acceptance and awareness of the breath. Four saliva cortisol samples were selected during the session. Results: Compared to induced rumination, distra…

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Stress pathways to spontaneous preterm birth: the role of stressors, psychological distress, and stress hormones.

The authors investigated a large number of stressors and measures of psychological distress in a multicenter, prospective cohort study of spontaneous preterm birth among 5,337 Montreal (Canada)-area women who delivered from October 1999 to April 2004. In addition, a nested case-control analysis (207 cases, 444 controls) was used to explore potential biologic pathways by analyzing maternal plasma corticotrophin-releasing hormone (CRH), placental histopathology, and (in a subset) maternal hair cortisol. Among the large number of stress and distress measures studied, only pregnancy-related anxiety was consistently and independently associated with spontaneous preterm birth (for values above the median, adjusted odds ratio = 1.8 (95% confidence interval: 1.3, 2.4)), with a dose-response relation across quartiles. The maternal plasma CRH concentration was significantly higher in cases than in…

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Cortisol response to stress in female youths exposed to childhood maltreatment: results of the youth mood project.

Background: Few studies have examined stress reactivity and its relationship to major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) among maltreated youth. We examined differences between maltreated and control participants in heart rate and cortisol resting and reactivity levels in response to a psychosocial stressor. Methods: We recruited 67 female youths aged 12 to 16 with no prior history of depression from child protection agencies and a control group of 25 youths matched on age and postal code. Child maltreatment was measured with two self-report instruments. Psychiatric status was assessed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Results: Piecewise multilevel growth curve analysis was used to model group differences in resting and reactivity cortisol levels and heart rate in response to the Trier Social Stress Test…

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Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals.

Chronic alcohol abuse is associated with changes in stress and reward pathways that could alter vulnerability to emotional stress and alcohol craving. This study examines whether chronic alcohol abuse is associated with altered stress and alcohol craving responses. Treatment-engaged, 28-day abstinent alcohol-dependent individuals (ADs; 6F/22M), and social drinkers (SDs; 10F/18M) were exposed to a brief guided imagery of a personalized stressful, alcohol-related and neutral-relaxing situation, one imagery condition per session, presented in random order across 3 days. Alcohol craving, anxiety and emotion ratings, behavioral distress responses, heart rate, blood pressure, and salivary cortisol measures were assessed. Alcohol patients showed significantly elevated basal heart rate and salivary cortisol levels. Stress and alcohol cue exposure each produced a significantly enhanced and persis…

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Abnormal insulin sensitivity persists up to three years in pediatric patients post-burn.

Context: The acute hypermetabolic response post-burn is associated with insulin resistance and hyperglycemia, significantly contributing to adverse outcome of these patients. Objective: The aim of the study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree of insulin resistance in severely burned children for up to 3 yr after the burn injury. Design, setting and patients: A total of 194 severely burned pediatric patients, admitted to our institute between 2002 and 2007, were enrolled in this prospective study and compared to a cohort of 95 nonburned, noninjured children. Main outcome measures: Urinary cortisol, epinephrine, and norepinephrine, serum cytokines, and resting energy requirements were determined at admission and 1, 2, 6, 9, 12, 18, 24, and 36 months post-burn. A 75-g oral glucose tolerance test was performed …

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Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex.

Background: Acute psychological stress impairs higher-order cognitive function such as working memory (WM). Similar impairments are seen in various psychiatric disorders that are associated with higher susceptibility to stress and with prefrontal cortical dysfunctions, suggesting that acute stress may play a potential role in such dysfunctions. However, it remains unknown whether acute stress has immediate effects on WM-related prefrontal activity. Methods: Using functional magnetic resonance imaging (fMRI), we investigated neural activity of 27 healthy female participants during a blocked WM task (numerical N-back) while moderate psychological stress was induced by viewing strongly aversive (vs. neutral) movie material together with a self-referencing instruction. To assess stress manipulation, autonomic and endocrine, as well as subjective, measurements were acquired throughout the exp…

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Mother-adolescent physiological synchrony in naturalistic settings: within-family cortisol associations and moderators.

In this study, the authors examined parent-adolescent cortisol associations in 45 families with adolescent children (24 girls; M age = 15.78 years, SD = 1.44 years). Family members' salivary cortisol levels were measured seven times a day on 2 typical weekdays. Family members provided reports of demographic and health variables, and adolescents rated parent-child relationship characteristics. After accounting for the effects of time of day and relevant demographic and health control variables on cortisol levels, hierarchical linear models indicated the presence of significant covariation over time in mother-adolescent cortisol (i.e., physiological synchrony). Furthermore, moderating tests revealed that mother-adolescent cortisol synchrony was strengthened among dyads characterized by mothers and adolescents spending more time together, and in families rated higher on levels of parent-you…

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The level of physical activity affects adrenal and cardiovascular reactivity to psychosocial stress.

Physical activity plays a key role in the control of neuroendocrine, autonomic, and behavioral responses to physical and psychosocial stress. However, little is known about how the level of physical activity modulates stress responsiveness. Here, we test whether different levels of physical activity are associated with different adrenal, cardiovascular, and psychological responses to psychosocial stress. In addition, competitiveness is assessed as a personality trait that possibly modulates the relationship between physical activity and stress reactivity. Eighteen elite sportsmen, 50 amateur sportsmen, and 24 untrained men were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Repeated measures of salivary free cortisol, heart rate, and psychological responses to psychosocial stress were compared among the 3 study groups. Elite sportsmen exhibited sig…

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Stress and emotional memory retrieval: effects of sex and cortisol response.

In some situations, memory is enhanced by stressful experience, while in others, it is impaired. The specific components of the stress-response that may result in these differing effects remain unclear, and the current study sought to address this knowledge gap. Forty healthy participants (20 women, 20 men) were exposed to emotionally arousing and neutral pictures. Twenty-four hours later, 20 participants underwent a social stressor (speech and math tests), and 20 underwent a control reading task, both followed by a delayed free recall task. Cortisol responders to the stress condition (5 men and 1 woman) showed reduced memory retrieval for both neutral and emotionally arousing pictures. Men and women in the stress condition who did not produce a cortisol response showed increased retrieval of unpleasant pictures compared to controls. The results provide further evidence that cortisol is …

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Multiple aspects of the stress response under social evaluative threat: an electrophysiological investigation.

Affective traits and states may be important moderators of stress reactivity, providing insight into stress-related consequences on cognitive functioning. This study assessed cognitive control processes using response-related brain electrical activities-the error-related negativity (ERN) and error positivity (Pe)-that are sensitive to trait and state affect. To assess the role of cognitive control in affective and cortisol reactivity to social evaluative threat, 55 undergraduates first completed a standard task designed to elicit the ERN in order to index 'baseline' error monitoring. Participants then performed a difficult mathematical task designed to elicit the ERN under conditions of exposed failure and social evaluation. Baseline ERN amplitude predicted future cortisol reactivity to social evaluative threat in highly punishment-sensitive individuals (high self-reported Behavioral Inh…

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Development of the corticosteroid stress axis and receptor expression in zebrafish.

Using zebrafish embryos and larvae, we examined the temporal patterns of cortisol and expression of genes involved in corticosteroid synthesis and signaling. Embryonic cortisol levels decreased approximately 70% from 1.5 h postfertilization (hpf) to hatch (approximately 42 hpf) and then increased 27-fold by 146 hpf. The mRNA abundances of steroidogenic acute regulatory protein, 11beta-hydroxylase and 11beta-hydroxysteroid dehydrogenase type 2, increased severalfold after hatch and preceded the rise of cortisol levels. In contrast to other teleosts that possess two glucocorticoid receptors (GRs) and one mineralocorticoid receptor (MR), only one GR and MR were identified in zebrafish, which were cloned and sequenced. GR mRNA abundance decreased from 1.5 to 25 hpf, rebounded, and then was stable from 49 to 146 hpf. MR transcripts increased continuously from 1.5 hpf and were 52-fold higher b…

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Homeless street children in Nepal: use of allostatic load to assess the burden of childhood adversity.

As challenges to child well-being through economic disadvantage, family disruption, and migration or displacement escalate world wide, the need for cross-culturally robust understanding of childhood adversity proportionately increases. Toward this end, developmental risk was assessed in four contrasting groups of 107 Nepali children ages 10-14 years that represent distinctive, common conditions in which contemporary children grow up. Relative cumulative burden (allostatic load) indexed by multiple dimensions of physical and psychosocial stress was ascertained among homeless street boys and three family-based groups, from poor urban squatter settlements, urban middle class, and a remote rural village. Biomarkers of stress and vulnerability to stress included growth status, salivary cortisol, antibodies to Epstein-Barr virus, acute phase inflammatory responses (alpha1-antichymotrypsin), an…

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Effects of pre-learning stress on memory for neutral, positive and negative words: Different roles of cortisol and autonomic arousal.

Stress can have enhancing or impairing effects on memory. Here, we addressed the effect of pre-learning stress on subsequent memory and asked whether neutral and emotionally valent information are differentially affected by specific stress components, autonomic arousal and stress-induced cortisol. Ninety-six healthy men and women underwent either a stressor (modified cold pressor test) or a control warm water exposure. During stress, participants showed comparable autonomic arousal (heart rate, blood pressure), while 60 percent showed an increase of cortisol (responders vs. 40 percent non-responders). Ten minutes after the cold pressor test neutral, positive and negative words were presented. Free recall was tested 1 and 24h later. Overall, positive and negative words were better recalled than neutral words. Stress enhanced the recall of neutral words independently of cortisol response. …

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Gender difference in neural response to psychological stress.

Gender is an important biological determinant of vulnerability to psychosocial stress. We used perfusion based functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) responses to mild to moderate stress in 32 healthy people (16 males and 16 females). Psychological stress was elicited using mental arithmetic tasks under varying pressure. Stress in men was associated with CBF increase in the right prefrontal cortex (RPFC) and CBF reduction in the left orbitofrontal cortex (LOrF), a robust response that persisted beyond the stress task period. In contrast, stress in women primarily activated the limbic system, including the ventral striatum, putamen, insula and cingulate cortex. The asymmetric prefrontal activity in males was associated with a physiological index of stress responses-salivary cortisol, whereas the female limbic activation showed a lower degree of c…

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Childhood poverty and health: cumulative risk exposure and stress dysregulation.

A massive literature documents the inverse association between poverty or low socioeconomic status and health, but little is known about the mechanisms underlying this robust relation. We examined longitudinal relations between duration of poverty exposure since birth, cumulative risk exposure, and physiological stress in two hundred seven 13-year-olds. Chronic stress was assessed by basal blood pressure and overnight cortisol levels; stress regulation was assessed by cardiovascular reactivity to a standard acute stressor and recovery after exposure to this stressor. Cumulative risk exposure was measured by multiple physical (e.g., substandard housing) and social (e.g., family turmoil) risk factors. The greater the number of years spent living in poverty, the more elevated was overnight cortisol and the more dysregulated was the cardiovascular response (i.e., muted reactivity). Cardiovas…

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Racial/ethnic differences in cortisol diurnal rhythms in a community sample of adolescents.

Purpose: To identify potential physiological pathways to racial disparities in health outcomes, this study uses cortisol data collected from a community sample of 255 adolescents to examine whether there are racial/ethnic differences in cortisol slopes and levels across the waking day in naturalistic settings. Methods: This study uses salivary cortisol data (sampled five times per day over 3 days) to examine racial/ethnic differences in diurnal cortisol rhythms, while covarying the presence of major depressive disorder and chronic and episodic life stress (assessed by structured interviews), momentary negative emotion (reported in diaries completed with cortisol samples), and socioeconomic status, sleep, and health variables (assessed by questionnaire) previously found to be associated with cortisol levels. Results: African-American and Hispanic youth were found to have flatter cortisol …

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Stress on the dance floor: the cortisol stress response to social-evaluative threat in competitive ballroom dancers.

The social self-preservation theory states that humans have a fundamental motivation to preserve the social self and that threats to the social self perturb biological markers such as cortisol. Five studies were designed to examine the cortisol response to competitive ballroom dancing as a paradigm for real-life social-evaluative threat. Competitive dancing produced substantial increases in cortisol compared to a control day. These increases were not due to the physical strain of dancing and were greater than those found during social-evaluative laboratory stressors. Responses did not habituate across competitions and were mostly elevated under highly focused conditions of threat (couple vs. group competition). These findings support the notion of a social self-preservation system that is physiologically responsive to threats to the social self.

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The psychosocial stress-induced increase in salivary alpha-amylase is independent of saliva flow rate.

The stress response of salivary alpha-amylase (sAA) has been suggested as an index for sympathetic nervous system activation. However, concurrent inhibition of the parasympathetic nervous system is discussed as a confounder due to suppression of saliva flow rate. Here we set out to test the influence of stress-induced changes in flow rate on sAA secretion. Twenty-six subjects underwent the Trier Social Stress Test and a control condition. Saliva was sampled by passive drooling or salivettes. Saliva flow rate, sAA levels and output, salivary cortisol, and heart rate variability were measured. Flow rate increased only when sampled by passive drooling. Stress-induced increases in amylase levels were correlated with increases of amylase output but not with flow rate. Results indicate that flow rate is not a confounder of stress-induced sAA activation and suggest that valid measurements of sA…

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Glucocorticoid release and memory consolidation in men and women.

Glucocorticoid hormones have been shown to enhance memory consolidation when applied at low doses posttraining, but are ineffective or impair memory at high doses. In a test of whether this quadratic relationship also exists for endogenously released glucocorticoids, healthy men and women received cold-pressor stress (CPS) or a control procedure immediately after reading a relatively neutral story and were tested for retention 1 week later. Cortisol levels in response to the stressor were assayed from saliva. CPS significantly elevated salivary cortisol in both sexes, but enhanced memory only in male subjects. Among CPS-treated male subjects, there was a significant quadratic correlation between cortisol release posttraining and subsequent memory. Thus, these findings represent the first demonstration of an inverted-U relationship between activity of endogenous stress hormones and human …

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The effect of maternal PTSD following in utero trauma exposure on behavior and temperament in the 9-month-old infant.

Unlabelled: In view of evidence of in utero glucocorticoid programming, and our prior observation of lower cortisol levels in 9-month-old infants of mothers with posttraumatic stress disorder (PTSD) compared to mothers without PTSD, we undertook an examination of the effect of in utero maternal stress, as determined by PTSD symptom severity, and maternal cortisol levels on behavioral outcomes in the infant. Methods: Ninety-eight pregnant women directly exposed to the World Trade Center (WTC) collapse on 9/11 provided salivary cortisol samples and completed a PTSD symptom questionnaire and a behavior rating scale to measure infant temperament, including distress to limitations, and response to novelty. Results: Mothers who developed PTSD in response to 9/11 had lower morning and evening salivary cortisol levels, compared to mothers who did not develop PTSD. Maternal morning cortisol level…

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