Higher Baseline Cortisol Levels Research Articles

Biobehavioral reactivity to social evaluative stress in women with borderline personality disorder.

Several clinical theories propose that borderline personality disorder (BPD) is characterized by a biologically based affective vulnerability to intense affective experiences and impaired modulation of affective states, which might manifest in high emotional intensity, hyperreactivity, and impaired recovery to baseline. However, few studies have tested these theories based on emotional and biological responses of BPD participants in response to psychosocial stressors. This study examined cortisol, alpha-amylase, and subjective emotional reactivity to social evaluative stress among women with BPD compared with two healthy female control groups: a trait-matched (TM) group scoring similarly to the BPD group on trait measures of negative affect and impulsivity, and a non-trait-matched (NTM) group. Results generally suggested high emotional intensity and high baseline psychobiological arousal among individuals with BPD, but not emotional hyperreactivity or impaired recovery specific to the stressor. Relative to both control groups, BPD participants had higher baseline and overall subjective negative affect, higher baseline cortisol levels, and attenuated stress-related cortisol reactivity. In addition, both the BPD and TM groups had attenuated alpha-amylase reactivity in comparison to the NTM group. The differences between BPD and TM groups on most of the dependent measures suggest that emotional dysregulation in BPD is not merely an extreme variant of normative personality traits. These results suggest that women with BPD demonstrate intense and chronic negative affectivity along with high resting psychobiological arousal and attenuated psychobiological reactivity specific to laboratory stressors.

The effect of temperament and responsiveness towards humans on the behavior, physiology and milk production of multi-parous dairy cows in a familiar and novel milking environment

The objectives of this study were to investigate whether; 1) temperament or 2) behavioral responsiveness to humans, can affect the behavior, physiology and productivity of dairy cows being milked in a familiar and novel milking environment. Temperament of multi-parous cows was defined based on exit time from a restraint device, as High Responders (HR; n=10), Medium Responders (MR; n=10) or Low Responders (LR; n=10). The behavioral response of cows to humans was assessed using four tests: restraint, exit speed, avoidance distance test and a voluntary approach test. Cows were milked according to their established routines in a rotary (familiar) milking parlor and behavioral, physiological and production data were collected over five consecutive days, including heart rate, cortisol and oxytocin concentrations and milk yield. The following week, cows were milked in a novel environment (herringbone parlor within the same farm facility) over five consecutive days, and the data and sample collection program was repeated. Cows were then given an exogenous adrenocorticotropic hormone (ACTH) challenge to measure adrenal responsiveness. Exit time was negatively correlated with the behavioral responses of cows to restraint and human avoidance distance (HAD) in the paddock and arena. The behavioral response of cows to the milking process was greater in MR than LR and HR cows in the familiar and novel milking environments. Milk yields were greater in LR than HR cows in the novel but not the familiar milking parlor. Oxytocin concentrations increased during milking in the novel environment, regardless of cow temperament. In the familiar and novel environments, heart rates were higher in HR than LR cows before and during milking and rMSSD was lower in HR cows during milking in a novel environment. There was no difference in cortisol concentrations between LR and HR cows in response to an ACTH challenge, but HR cows had higher baseline cortisol levels than LR cows. The number of leg lifts cows performed when restrained in the crush was associated with several physiological and milk production measures. These results indicate that cows with different temperaments vary in their basal physiology as well as their behavioral and physiological responses to milking and stress associated with being milked in a novel environment.

Consequences of acute stress and cortisol manipulation on the physiology, behavior, and reproductive outcome of female Pacific salmon on spawning grounds

Life-history theory predicts that stress responses should be muted to maximize reproductive fitness. Yet, the relationship between stress and reproduction for semelparous salmon is unusual because successfully spawning individuals have elevated plasma cortisol levels. To tease apart the effects of high baseline cortisol levels and stress-induced elevation of cortisol titers, we determined how varying degrees of cortisol elevation (i.e., acute and chronic) affected behavior, reproductive physiology, and reproductive success of adult female pink salmon (Oncorhynchus gorbuscha) relative to different states of ovulation (i.e., ripe and unripe). Exhaustive exercise and air exposure were applied as acute stressors to manipulate plasma cortisol in salmon either confined to a behavioral arena or free-swimming in a spawning channel. Cortisol (eliciting a cortisol elevation to levels similar to those in post-spawn female salmon) and metyrapone (a corticosteroid synthesis inhibitor) implants were also used to chemically manipulate plasma cortisol. Cortisol implants elevated plasma cortisol, and impaired reproductive success; cortisol-treated fish released fewer eggs and died sooner than fish in other treatment groups. In contrast, acute stressors elevated plasma cortisol and the metyrapone implant suppressed plasma cortisol, but neither treatment significantly altered reproductive success, behavior, or physiology. Our results suggest that acute stressors do not influence behavior or reproductive outcome when experienced upon arrival at spawning grounds. Thus, certain critical aspects of salmonid reproduction can become refractory to various stressful conditions on spawning grounds. However, there is a limit to the ability of these fish to tolerate elevated cortisol levels as revealed by experimental elevation of cortisol.

A Prospective Multicenter Study of Adrenal Function in Critically Ill Children

Adrenal insufficiency is a clinical condition associated with fluid- and catecholamine-resistant hypotension. The objectives of this study were to determine the prevalence of adrenal insufficiency, risk factors and potential mechanisms for its development, and its association with clinically important outcomes in critically ill children. A prospective, cohort study was conducted from 2005 to 2008 in seven tertiary-care, pediatric intensive care units in Canada on patients up to 17 years of age with existing vascular access. Adrenocorticotropic hormone stimulation tests (1 microg) were performed and adrenocorticotropic hormone levels measured in all participants. A total of 381 patients had adrenal testing on admission. The prevalence of adrenal insufficiency was 30.2% (95% confidence interval, 25.9-35.1). Patients with adrenal insufficiency had higher baseline cortisol levels (28.6 microg/dl vs. 16.7 microg/dl, P < 0.001) and were significantly older (11.5 yr vs. 2.3 yr, P < 0.001) than those without adrenal insufficiency. Adrenal insufficiency was associated with an increased need for catecholamines (P < 0.001) and more fluid boluses (P = 0.026). The sensitivity and specificity of the low-dose adrenocorticotropic hormone stimulation test were 100% and 84%, respectively. Adrenal insufficiency occurs in many disease conditions in critically ill children and is associated with an increased use of catecholamines and fluid boluses. It is likely multifactorial in etiology and is associated with high baseline cortisol levels. Further research is necessary to determine which of these critically ill children are truly cortisol deficient before any treatment recommendations can be made.

Acute tryptophan depletion increases experimental nausea but also induces hunger in healthy female subjects

Acute tryptophan depletion (ATD) is an experimental model to reduce central serotonin levels. Thirty-eight healthy female subjects were randomly assigned to two groups (ATD and control) in a randomized, double-blinded parallel-group design. Following a standardized and balanced amino acid diet (including 1.21 g tryptophan) on the first day, they received either a protein drink without tryptophan (but substituted by other amino acids) (ATD condition) or the balanced protein drink with tryptophan (control condition) 24 h later. Four hours after its consumption, they were exposed to a standard rotation procedure. Symptom ratings (SR), ratings of hunger and mood scores were taken prior to rotation, at each break, and 15 and 30 min thereafter, together with saliva cortisol samples. Five subjects could not tolerate the entire rotation procedure and were excluded from analysis. For the remaining n = 33, SR and hunger ratings were higher during ATD than during control conditions, but mood was unaffected. Cortisol levels rose significantly with rotation but were unaffected by ATD. High baseline cortisol levels were associated with lower SR during rotation. The protective effects of morning cortisol were pronounced during the menstrual and follicular phase of the cycle and not present during ovulation and the luteal phase. Acute tryptophan depletion is associated with increased symptoms of nausea in healthy female subjects when exposed to body rotation. Acute tryptophan depletion also increases hunger rating. These opposite effects may indicate independent actions of the serotonin on central and peripheral functions.

Cytokine Inhibition after Glucocorticoid Exposure in Healthy Men with Low versus High Basal Cortisol Levels

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. Methods:136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m²) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. Results:After exposure to DEX in vivo, inhibition of IL-6 and TNF-α decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.

Diagnosis and Treatment of Adrenal Insufficiency in the Critically Ill Patient

The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the test and cutoff levels used, and the severity of illness. Several studies have shown increased mortality in patients with very low or very high baseline cortisol levels. Manifestations of adrenal insufficiency in the critically ill patient are numerous and nonspecific, so clinicians are urged to have a high index of suspicion and be alert to important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension, that are refractory to fluids and vasopressors without any clear causation. Multiple tests have been developed to diagnose adrenal insufficiency, but the most commonly used test in the intensive care unit is the adrenocorticotropic hormone (ACTH) stimulation test. The low-dose ACTH stimulation test has been shown to be more sensitive and specific than the high-dose test; however, the high-dose test is preferred since the low-dose test has not been validated. Although diagnosing adrenal insufficiency continues to be difficult in the critically ill patient, administration of high-dose corticosteroids, defined as methylprednisolone 30 mg/kg/day or more (or its equivalent), over a short period of time provides no overall benefit and may even be harmful; however, administration of low-dose corticosteroids for a longer duration decreases both the amount of the time that vasopressors are required and mortality at 28 days. Hydrocortisone 200-300 mg/day, administered in divided doses or as a continuous infusion, is the preferred corticosteroid in patients with septic shock and should be started as early as possible. For patients in whom the ACTH stimulation test cannot be given immediately, clinicians are urged to consider using dexamethasone until such time that the test can be administered, since, unlike hydrocortisone, it does not interfere with the cortisol test.

Shyness is a necessary but not sufficient condition for high salivary cortisol in typically developing 10 year-old children

Previous research has noted both high and low baseline cortisol levels in anxious personality styles. We examined the relations among shyness, baseline salivary cortisol, and resting heart rate in a non-clinical sample of 10-year-old children. As predicted, shyness was positively correlated with baseline salivary cortisol and resting heart rate, replicating and extending earlier work with preschool age children to middle childhood. However, post-hoc analyses revealed that the scatterplot of shyness and salivary cortisol was significantly triangular in shape, indicating that shyness was a necessary, but not sufficient, condition for high salivary cortisol at age 10. For children high in shyness, salivary cortisol levels ranged from low to high; for children low in shyness, salivary cortisol levels were low. This triangular pattern was not found for the association between shyness and resting heart rate, suggesting different roles of neuroendocrine and autonomic measures in relation to shyness. The potential roles of cortisol in the maintenance of shyness developmentally are discussed as are the broader implications for clarifying prior inconsistent results on the relation between temperament and cortisol in humans. The use of triangular data analytic strategies for interpreting relations between psychological variables and identification of risk and protective factors is also discussed.

Adrenal function in sepsis: The retrospective Corticus cohort study

To refine the value of baseline and adrenocorticotropin hormone (ACTH)-stimulated cortisol levels in relation to mortality from severe sepsis or septic shock. Retrospective multicenter cohort study. Twenty European intensive care units. Patients included 477 patients with severe sepsis and septic shock who had undergone an ACTH stimulation test on the day of the onset of severe sepsis. None. Compared with survivors, nonsurvivors had higher baseline cortisol levels (29.5 +/- 33.5 vs. 24.3 +/- 16.5 microg/dL, p = .03) but similar peak cortisol values (37.6 +/- 40.2 vs. 35.2 +/- 22.9 microg/dL, p = .42). Thus, nonsurvivors had lower Deltamax (i.e., peak cortisol minus baseline cortisol) (6.4 +/- 22.6 vs. 10.9 +/- 12.9 microg/dL, p = .006). Patients with either baseline cortisol levels <15 microg/dL or a Deltamax <or=9 microg/dL had a likelihood ratio of dying of 1.26 (95% confidence interval, 1.11-1.44), a longer duration of shock, and a shorter survival time. Patients with a Deltamax <or=9 microg/dL but any baseline cortisol value had a likelihood ratio of dying of 1.38 (95% confidence interval, 1.18-1.61). Although delta cortisol and not basal cortisol level was associated with clinical outcome, further studies are still needed to optimize the diagnosis of adrenal insufficiency in critical illness. Etomidate influenced ACTH test results and was associated with a worse outcome.

Role of Cortisol in Menstrual Recovery in Adolescent Girls with Anorexia Nervosa

Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr x m2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN.

Adrenal insufficiency in sepsis

Corticosteroids were introduced in the treatment of severe infection as early as in the nineteen forties. Several " negative" randomized controlled trials of high-dose of glucocorticoids given for a short period of time in the early course of severe sepsis or acute respiratory distress syndrome raised serious doubts on the benefit of this treatment. Recently, a link between septic shock and adrenal insufficiency, or systemic inflammation induced glucocorticoids receptor resistance had been established. This finding prompted renewed interest of a replacement therapy with low doses of corticosteroids during longer periods. The goal of this article is to review the key role of corticosteroids in the host response to stress and will update the reader with the new validated indications of corticosteroids treatment in the ICU. Extensive review of the adrenal physiology and its pathophysiological derangements and clinical implications in critically ill patients. During sepsis, hemodynamic instability and perpetuation of inflammatory state may result from adrenal insufficiency (AI). Thus, an ACTH test should be performed as soon as possible to identify non overt AI. It should be immediately followed by a replacement therapy with iv bolus of 50 mg of hydrocortisone every 6 hours combined to 50 µg of fludrocortisone once daily. When the results of the ACTH test are available, treatment should be continued for 7 days in the non responders to ACTH and withdraw in the responders. Whether responders to ACTH with high baseline cortisol levels (> 34 µg/dL) have tissue resistance to cortisol and also should receive exogenous hormones remains to be evaluated in clinical trials.

Pro-Con Debate: Steroid use in ACTH non-responsive septic shock patients with high baseline cortisol levels

Steroid use in critically ill, vasopressor-dependant, septic patients has gained increased acceptance in recent years with the publication of encouraging data. However, with renewed interest and/or attention comes increased debate and analysis. As a result, it is not surprising to find that there is still significant controversy with regards to the role of steroids in many patients. In this article, two expert groups debate the role of steroid use in a septic shock patient with arguably no clear evidence of adrenal insufficiency.

Neuroendocrine response to an intravenous L-tryptophan challenge in women with premenstrual syndrome

Objective: To evaluate the neuroendocrine responses to an intravenous L-tryptophan challenge across the menstrual cycle in women with premenstrual syndrome (PMS) and controls. Design: Controlled clinical study. Setting: The Clinical Research Center of an academic research environment. Patient(s): Women with PMS and healthy volunteers. Intervention(s): An intravenous L-tryptophan challenge was administered two times a week during 1 month to five subjects with prospectively documented PMS and five age- and body mass-matched controls. Main Outcome Measure(s): Whole-blood serotonin, cortisol, and prolactin levels were assessed at the baseline and at 30, 50, 60, 70, 80, and 90 minutes after the challenge. Result(s): Whole-blood serotonin response to the L-tryptophan challenge was blunted in the luteal phase of the menstrual cycle in subjects with PMS compared with controls. Cortisol levels differed between groups and cycle phases only at the baseline, with higher baseline cortisol levels during the luteal phase in women with PMS, whereas baseline and postchallenge prolactin levels did not differ between groups. Conclusion(s): The present results support previously reported findings of alterations in tryptophan handling in women with PMS. The elevated baseline luteal phase cortisol concentrations in subjects with PMS warrants further investigation.

Influence of housing conditions on responses of pigs to preslaughter treatment and consequences for meat quality

The effects of housing conditions on behavioural and cortisol responses during preslaughter treatment, as well as the consequences for meat quality, were studied in 48 slaughter pigs. Pigs were either raised in intensive housing conditions ("standard" treatment: standard farrowing crates (4.2 m2) followed by standard rearing pens (0.5 m2/pig) and fattening pens (0.8 m2/pig) or in extensive conditions ("enriched" treatment: larger farrowing pens (7.2 m2) followed by larger rearing and fattening pens (both 1.2 m2/pig), all provided with straw).No differences in behaviour during transport or in any of the meat quality variables were found between treatments. During pre-slaughter handling, stockmen needed significantly less time to load pigs from standard housing conditions (standard: 56.8 ± 11.9 s; enriched: 93.7 ± 12.5 s). Standard pigs may have been more motivated to leave their pens in order to explore another environment than pigs from the enriched housing pens. Rise in salivary cortisol levels due to transport (standard: 6.68 ± 0.80 ng mL−1; enriched: 3.63 ± 0.58 ng mL−1) was difficult to interpret as omission of straw during the hours prior to transport apparently led to high baseline cortisol levels in enriched pigs (8.63 ± 1.27 ng mL−1 vs. 2.60 ± 0.37 ng mL−1 in standard pigs). The extensive housing system should be preferred as it is known to have positive effects on pig welfare, and does not lead to impaired meat quality. Key words: Behaviour, housing, meat quality, physiology, pigs, slaughter

Prolactin and cortisol responses to d-fenfluramine in major depression: evidence for diminished responsivity of central serotonergic function

Theoretically, d-fenfluramine should be a more selective serotonin (5-HT) challenge agent and has much greater clinical tolerance than the racemic compound that has previously been used. The authors' goal, therefore, was to look at 5-HT function in depression using the d isomer of fenfluramine as a probe. They evaluated central 5-HT function in 23 patients with DSM-III-R-diagnosed major depression and 16 healthy control subjects. The depressed group included 10 men and 13 women; four were outpatients, two attended a day hospital facility, and 17 were inpatients. Subjects were cannulated at 8:30 a.m. after an overnight fast. After baseline samples were drawn, 30 mg of d-fenfluramine was administered orally and blood samples were drawn over the following 5-hour period for prolactin and cortisol estimation. The plasma prolactin responses of the depressed patients were significantly lower than those of the control subjects. This blunting was not related to the severity of the depression but was significantly related to the patients' levels of state anxiety. Cortisol responses as well as prolactin responses were impaired in depression. High baseline cortisol levels were correlated with the severity of depression and the presence of weight loss. Overall, these findings indicate that there is diminished 5-HT responsivity in the depressed state.