Acute Administration Of Hydrocortisone Research Articles

Traumatic imagery following glucocorticoid administration in earthquake-related post-traumatic stress disorder: A preliminary functional magnetic resonance imaging study.

Post-traumatic stress disorder involves excessive retrieval of traumatic memories. Glucocorticoids impair declarative memory retrieval. This preliminary study examined the effect of acute hydrocortisone administration on brain activation in individuals with earthquake-related post-traumatic stress disorder compared with earthquake-exposed healthy individuals, during retrieval of traumatic memories. Participants exposed to earthquakes with (n = 11) and without post-traumatic stress disorder (n = 11) underwent two functional magnetic resonance imaging scans, 1-week apart, in a double-blind, placebo-controlled, counter-balanced design. On one occasion, they received oral hydrocortisone (20 mg), and on the other, placebo, 1 hour before scanning. Symptom provocation involved script-driven imagery (traumatic and neutral scripts) and measures of self-reported anxiety. Arterial spin labelling showed that both post-traumatic stress disorder and trauma-exposed controls had significantly reduced cerebral blood flow in response to retrieval of traumatic versus neutral memories in the right hippocampus, parahippocampal gyrus, calcarine sulcus, middle and superior temporal gyrus, posterior cingulate, Heschl's gyrus, inferior parietal lobule, angular gyrus, middle occipital gyrus, supramarginal gyrus, lingual gyrus and cuneus, and the left prefrontal cortex. Hydrocortisone resulted in non-significant trends of increasing subjective distress and reduced regional cerebral blood flow in the left inferior frontal gyrus, left anterior cingulate gyrus, middle temporal gyrus, cerebellum, postcentral gyrus and right frontal pole, during the trauma script. Findings do not fit with some aspects of the accepted neurocircuitry model of post-traumatic stress disorder, i.e., failure of the medial prefrontal cortex to quieten hyperresponsive amygdala activity, and the potential therapeutic benefits of hydrocortisone. They do, however, provide further evidence that exposure to earthquake trauma, regardless of whether post-traumatic stress disorder eventuates, impacts brain activity and highlights the importance of inclusion of trauma-exposed comparisons in studies of post-traumatic stress disorder.

Acute hydrocortisone administration reduces cardiovagal baroreflex sensitivity and heart rate variability in young men.

Key points A surge in cortisol during acute physiological and pathophysiological stress may precipitate ventricular arrhythmia and myocardial infarction.Reduced cardiovagal baroreflex sensitivity and heart rate variability are observed during acute stress and are associated with an increased risk of acute cardiac events.In the present study, healthy young men received either a single iv bolus of saline (placebo) or hydrocortisone, 1 week apart, in accordance with a randomized, placebo‐controlled, cross‐over study design.Hydrocortisone acutely increased heart rate and blood pressure and reduced cardiovagal baroreflex sensitivity and heart rate variability in young men.These findings suggest that, by reducing cardiovagal baroreflex sensitivity and heart rate variability, acute surges in cortisol facilitate a pro‐arrhythmic milieu and provide an important mechanistic link between stress and acute cardiac events Surges in cortisol concentration during acute stress may increase cardiovascular risk. To better understand the interactions between cortisol and the autonomic nervous system, we determined the acute effects of hydrocortisone administration on cardiovagal baroreflex sensitivity (BRS), heart rate variability (HRV) and cardiovascular reactivity. In a randomized, placebo‐controlled, single‐blinded cross‐over study, 10 healthy males received either a single iv bolus of saline (placebo) or 200 mg of hydrocortisone, 1 week apart. Heart rate (HR), blood pressure (BP) and limb blood flow were monitored 3 h later, at rest and during the sequential infusion of sodium nitroprusside and phenylephrine (modified Oxford Technique), a cold pressor test and a mental arithmetic stress task. HRV was assessed using the square root of the mean of the sum of the squares of differences between successive R‐R intervals (rMSSD). Hydrocortisone markedly increased serum cortisol 3 h following infusion and also compared to placebo. In addition, hydrocortisone elevated resting HR (+7 ± 4 beats min−1; P < 0.001) and systolic BP (+5 ± 5 mmHg; P = 0.008); lowered cardiovagal BRS [geometric mean (95% confidence interval) 15.6 (11.1–22.1) ms/mmHg vs. 26.2 (17.4––39.5) ms/mmHg, P = 0.011] and HRV (rMSSD 59 ± 29 ms vs. 84 ± 38 ms, P = 0.004) and increased leg vasoconstrictor responses to cold pressor test (Δ leg vascular conductance −45 ± 20% vs. −23 ± 26%; P = 0.023). In young men, an acute cortisol surge is accompanied by increases in HR and BP, as well as reductions in cardiovagal BRS and HRV, potentially providing a pro‐arrhythmic milieu that may precipitate ventricular arrhythmia or myocardial infarction and increase cardiovascular risk.

Acute glucocorticoid effects on response inhibition in borderline personality disorder

Growing evidence suggests inhibition dysfunctions in borderline personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis functioning have also been found in BPD patients. In healthy individuals, response inhibition has been sensitive to acute stress, and previous research indicates that effects mediated by the HPA axis become particularly apparent when emotional stimuli are processed. This study aimed to explore the influence of acute hydrocortisone administration on response inhibition of emotional stimuli in BPD patients compared to healthy control participants. After a single administration of 10mg hydrocortisone or placebo, 32 female BPD patients and 32 healthy female participants performed an adapted emotional go/no-go paradigm to assess response inhibition for emotional face stimuli in a cross-over study. Acute cortisol elevations decreased the reaction times to target stimuli in both BPD patients and healthy controls. Patients and controls did not differ in task performance; however, BPD patients with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction times than patients without PTSD. In contrast, the occurrence of comorbid eating disorder had no significant impact on go/no-go performance. No significant interaction effect between the treatment condition and the emotional valence of the face stimuli was found. Acute hydrocortisone administration enhances response inhibition of face stimuli in BPD patients and healthy controls, regardless of their emotional valence. Our results agree with the suggestion that moderate cortisol enhancement increases the inhibition of task-irrelevant distracters.

Detection of the acute effects of hydrocortisone in the hippocampus using pharmacological fMRI

Impaired hippocampal function is believed to be important in the pathogenesis of depression. The hippocampus contains a high concentration of both mineralocorticoid (MR) and glucocorticoid receptors (GR), and the experimental administration of corticosteroids has been reported to mimic memory impairments seen in depression. Using pharmacological functional magnetic resonance imaging (phMRI) we investigated whether hippocampal function is altered after acute administration of hydrocortisone. Changes in BOLD signal following infusion of 100mg hydrocortisone given as a rapid intravenous bolus were measured in 14 healthy volunteers in a within-subject placebo-controlled crossover design. Subsequently, subjects completed an n-back task during an fMRI scan. Hydrocortisone infusion caused a significant, time-dependent increase in fMRI BOLD signal in hippocampus reaching a maximal effect at 11–19min. The n-back task increased BOLD signal in prefrontal and parietal cortical areas and decreased it in the hippocampus. After hydrocortisone the left hippocampal decrease in BOLD signal was attenuated with the magnitude of attenuation correlating with the increase seen after hydrocortisone infusion. No difference in behavioural task performance was observed. The results suggest acute hydrocortisone has rapid direct and modulatory influences on hippocampal function, probably acting through non-genomic GR or MR signalling. Hydrocortisone infusion phMRI may be a useful tool to investigate hippocampal corticosteroid receptor function in depression.

Effects of Acute Hydrocortisone Administration on Declarative Memory in Patients With Major Depressive Disorder

Major depressive disorder (MDD) has been associated with hypercortisolism, reduced glucocorticoid feedback sensitivity, and impaired memory function. In healthy subjects, administration of hydrocortisone impairs declarative memory. The aim of this study was to examine the effects of acute hydrocortisone administration on memory retrieval in MDD patients and healthy controls. We further tested whether the enhancing or impairing effects of hydrocortisone would prevail when it was given after encoding and when delayed retrieval was tested at a time point when glucocorticoid levels were still elevated. In a placebo-controlled, double-blind crossover study, 44 patients with DSM-IV MDD and 51 healthy control participants received either placebo or 10 mg of hydrocortisone orally before memory testing. A word list paradigm and the Logical Memory Test from the Wechsler Memory Scale were applied. The study was conducted from April 2008 until April 2010 at sites in Bielefeld and Hamburg, Germany. In both memory tests, patients with MDD performed worse than controls. Healthy controls showed impaired memory performance after hydrocortisone administration compared to placebo. In contrast, hydrocortisone had no effects on memory in MDD patients. Furthermore, in healthy controls we found that administration of hydrocortisone immediately after learning did not lead to an enhanced free recall during increased cortisol levels. It appears that the impairing effects of hydrocortisone on memory performance are missing in patients with MDD. This might be interpreted in the context of reduced central glucocorticoid receptor functioning.

Effect of cortisol levels on working memory performance in elderly subjects with Alzheimer's disease

Subjects with Alzheimer's disease (AD) have elevated cortisol levels as a result of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Acute administration of hydrocortisone has been associated with working memory (WM) performance in young adults. To investigate whether cortisol levels are associated with WM performance in subjects with AD. Eighty subjects were included, comprising 40 patients with mild AD and 40 healthy elderly controls. WM was assessed using the Digit Span Backward test (DSB). Saliva samples were collected to determine cortisol levels. AD subjects had poorer performance on the DSB than controls (p=0.002) and also presented higher levels of cortisol than control group (p=0.04). No significant correlation was observed between the DSB and cortisol levels in both groups (r= -0.29). In this study, elevated cortisol levels were not associated with poorer WM performance in patients with AD or in healthy elderly subjects.

Hydrocortisone increases the sensitivity to α1-adrenoceptor stimulation in humans following hemorrhagic shock*

To assess the pressor response to phenylephrine infusion before and after hydrocortisone in severe trauma patients and to correlate this response with their adrenal reserve. Prospective clinical study. Surgical intensive care unit in a university teaching hospital. Twenty-three young trauma patients (Injury Severity Score, 38 +/- 14) were studied at the end of the resuscitative period (27 +/- 15 hrs after trauma). Total cortisol response to intravenous corticotropin bolus (250 microg) was obtained. Total cortisol response <9 microg/dL defined an impaired adrenal function and the patient was called a nonresponder. Twelve to 24 hrs following this stimulation, phenylephrine was infused in a stepwise manner to establish the phenylephrine-mean arterial pressure dose-response curve before and after intravenous hydrocortisone administration (50 mg). An Emax model was used to describe the curve; the influence of the group (responder/nonresponder), the sequence (before/after hydrocortisone), and three covariates (Injury Severity Score, shock, and interleukin-6) were thereafter tested. Forty-three percent of patients were nonresponders. Total cortisol response was not correlated with serum albumin concentration and was negatively correlated with the interleukin-6 concentration. A trend for a higher incidence of nonresponders (53% vs. 36%) and a lesser total cortisol response (7.9 +/- 5.1 vs. 12.5 +/- 5.1 microg/dL) was observed in the shock patients. A phenylephrine dose-response structure (E0, ED50, and Emax) was described without influence of the group and the sequence. However, hydrocortisone induced a 37% decrease in ED50 without change in Emax in the shock patients. An acute administration of hydrocortisone increases the sensitivity to alpha1-adrenoceptor stimulation in fully resuscitated severe trauma patients following hemorrhagic shock. This effect is independent of the adrenal reserve of the patients and different from that previously reported in septic patients.

Chronic but Not Acute Hydrocortisone Treatment Shifts the Response to an Orthostatic Challenge towards Parasympathetic Activity

Adrenocortical steroid hormones play a major role in the regulation of both action and metabolism of catecholamines. However, there is limited information on the effect of prolonged increase in plasma steroid hormone concentration on the sympathetic nervous system, which is the main source of norepinephrine. Using a double-blind, placebo-controlled cross-over design, we examined 20 male healthy volunteers after acute administration of 40 mg hydrocortisone or matching placebo as well as after a 1-week treatment with this steroid (daily dose, 40 mg) or placebo. Sympathetic nervous system activity was assessed by determination of overnight urinary norepinephrine and epinephrine secretion and by analysis of short-time heart rate variability (HRV) measures in the frequency domain. The low-frequency (LF) component of the HRV spectrum was considered to reflect both sympathetic and parasympathetic modulation and the high-frequency (HF) band vagal activity. HRV testing included the response to a mild cardiovascular challenge, orthostasis. After 1 subject had been excluded because of incompliance with the study medication, the data of 19 subjects were used for further analyses. Prolonged hydrocortisone treatment was associated with a significant shift of relative power from the LF to the HF band in the upright position, resulting in a significant decrease in the LF/HF ratio (placebo 6.77 ± 3.35 and hydrocortisone 4.72 ± 3.27; p < 0.05). No differences between groups were observed after acute steroid administration or after prolonged treatment in the supine position. Neither acute nor chronic hydrocortisone treatment resulted in significant changes in the overnight urinary catecholamine secretion. Our data suggest that prolonged but not acute hydrocortisone administration shifts the autonomic response to an orthostatic challenge towards parasympathetic activity.

Lack of effect of a single dose of hydrocortisone on serotonin 1A receptors in recovered depressed patients measured by positron emission tomography with [ 11C]WAY-100635

Background Elevated cortisol levels might account for the reduction in central serotonin 1A (5-hydroxytryptamine [5-HT] 1A) receptor binding and function observed in patients with major depression. We tested this hypothesis by studying the effect of acute administration of hydrocortisone on 5-HT 1A receptor binding potential (BP) in subjects recovered from depression. Methods We studied 14 subjects (8 male, 6 female) who had recovered from at least two episodes of major depression and had been euthymic and drug free for at least 6 months. Serotonin 1A receptor BP was measured by [ 11C]WAY-100635 in conjunction with positron emission tomography. Subjects were tested on two occasions in a double-blind, random-order, crossover design after administration of either hydrocortisone (100 mg orally) or placebo 12 hours previously. Positron emission tomography scans were analyzed with a region of interest analysis. Results Hydrocortisone treatment did not decrease 5-HT 1A receptor BP either in the hippocampus, which was our a priori hypothesis, or in other cortical 5-HT 1A regions; however, female subjects had a higher 5-HT 1A receptor BP in certain brain areas compared with male subjects. Conclusions These data are consistent with an earlier study in healthy volunteers and do not support the proposal that decreased 5-HT 1A receptor BP in patients with acute major depression is a consequence of cortisol hypersecretion.

Hypothalamo-pituitary-adrenal function in patients with depressive disorders is correlated with baseline cytokine levels, but not with cytokine responses to hydrocortisone

Dysfunction of the hyopthalamo-pituitary adrenal (HPA) system is frequently found in major depression. In addition, signs of non-specific inflammatory system activation have been reported. However, very little is known about interactions between the HPA and immune systems in depressive patients. To assess HPA system function, we performed a combined dexamethasone suppression and corticotropin-releasing hormone stimulation (DEX/CRH) test in 14 depressive patients. Moreover, baseline nocturnal plasma levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were measured. In addition, the system was challenged with an intraveneous pulsatile injection of hydrocortisone (1 mg/kg body weight in total) and again cytokine levels were measured across one night. Baseline TNF-α levels were negatively correlated with the amount of ACTH released upon CRH stimulation during the DEX/CRH test. Acute hydrocortisone administration suppressed TNF-α and IL-6 levels independently of baseline HPA system activity. We conclude that chronic HPA system overactivity in depressed patients might compromise the production of inflammatory cytokines under baseline conditions. However, the responsivity of the cytokine production to acutely administered glucocorticoids does not seem to correlate with the state of the HPA system.

Acute hydrocortisone administration does not affect subjective responses to d-amphetamine in humans.

Stress and glucocorticoids facilitate and reinstate psychostimulant self-administration in rodents. However, the effects of stress and glucocorticoids on the subjective and behavioral effects of psychostimulants have not been well studied in humans. To examine the effects of acute hydrocortisone pretreatment on the subjective and behavioral effects of d-amphetamine. Hydrocortisone (100 mg) and d-amphetamine (20 mg) were administered orally to 16 healthy male and female volunteers in a four-session, placebo-controlled, within-subject, crossover design. To prevent stomach irritation, subjects received rantidine hydrochloride before each experimental session. Dependent measures included self-reported mood and subjective effects (Addiction Research Center inventory, the profile of mood states, and a series of visual analogue scales), vital signs, salivary cortisol, and psychomotor performance. Hydrocortisone elevated salivary cortisol levels, produced modest dysphoria, and reduced subjects' reports of wanting more drug. However, hydrocortisone pretreatment did not affect any of the physiological, behavioral, or subjective effects of d-amphetamine. In contrast to the effects of glucocorticoids in rodent studies, these results indicate that an acute increase in cortisol does not enhance the psychostimulant effects of d-amphetamine in humans.

Hydrocortisone administration and gastrin and gastric secretion in dogs.

Acute administration of hydrocortisone does not alter the serum gastrin levels appreciably. Corticosteroids, administered for five days in dogs, significantly increased basal serum gastrin levels as well as the serum gastrin response to a meat meal. The rise in serum gastrin levels after hydrocortisone stimulated a substantial increase in gastric acid output.

Progestin enhancement of the plasma insulin response to glucose in Rhesus monkeys.

Treatment of Rhesus monkeys with pure progesterone for three weeks produced enhanced plasma insulin responses to intravenous glucose without altering glucose tolerance, and mild, but significant peripheral resistance to the hypoglycemic action of exogenous insulin. Several synthetic progestins currently employed in oral contraceptive agents also increased the plasma insulin responses to glucose. These changes were in marked contrast to the effect of acute administration of hydrocortisone, where there was a marked deterioration of glucose tolerance without any significant alteration in the plasma insulin response to glucose. From the data presented it appears that glucose tolerance remains normal following progesterone treatment because of a marked compensatory enhancement of the initial rate of release of insulin into the peripheral circulation following glucose stimulation. The mechanisms by which progestins produce these changes and the relative importance of progesterone in normal human pregnancy remains to be determined. Nevertheless, these data suggest that pure progesterone, like human placental lactogen, may be a diabetogenic factor in pregnancy and indicate that some, but not all, of the synthetic progestins may contribute to the changes in glucose and insulin metabolism observed in women taking oral contraceptive agents.

The Effect of in Vitro and in Vivo Caffeine, Theophylline, and Hydrocortisone on the Phosphodiesterase Activity of the Pituitary, Median Eminence, Heart, and Cerebral Cortex of the Rat

SummaryThis study was undertaken to substantiate the thesis that the potentiation of the stress-induced secretion of ACTH by the methyl xanthines is due to their ability to inhibit the 3′5′-cyclic nucleotide phosphodiesterase. The effect of various drugs on the phosphodiesterase activity of the anterior pituitary, median eminence, brain cortex, and heart of rats was determined both in vitro and in vivo. Incubation of homogenates with caffeine and theophylline markedly reduced the phosphodiesterase activity in all tissues studied except heart, which showed a significant reduction only in the presence of theophylline. In contrast, pretreating the animals with a single dose of caffeine or theophylline reduced the enzyme activity of the anterior pituitary only, and caffeine was more effective than theophylline. Adrenalectomy, chronic or acute administration of hydrocortisone, or incubation of tissue homogenates with hydrocortisone or dexamethasone did not alter the phosphodiesterase activity of the tissues st...