Reduced Cortisol Levels Research Articles

77. Glucocorticoid receptor signaling is responsible for the circadian decline in naïve T cell numbers and increase in CXCR4 expression in the morning hours

One of the most pronounced circadian rhythms in human immune parameters is the decline in naïve T cell numbers from early night to morning. It is believed to be a consequence of CXCR4 up-regulation on T cells in the morning by cortisol with a subsequent extravasation of the cells. However, a systematic evaluation of this assumption is lacking. We therefore investigated in two human studies the consequences of blocking endogenous cortisol activity at glucocorticoid receptors (GR). This was done either by reducing cortisol levels with the cortisol-synthesis-inhibitor metyrapone or by administration of the GR antagonist mifepristone. In both studies, the morning increase in CXCR4 expression on naïve T cells was reduced or completely blocked after drug treatment. The parallel decline in naïve T cell numbers was also disturbed, although after mifepristone this result was less consistent. However, this might be due to the partial agonistic properties of mifepristone, which we observed in the early night and which we further characterized in subsequent in vitro experiments. To sum, we showed that endogenous cortisol, via activation of GR, mediates the circadian changes in naïve T cell numbers and CXCR4 expression. CXCR4 was revealed as a highly sensitive marker of GR signaling, and might be used in the future for drug monitoring. Additionally, we found partial agonistic effects after low-dose mifepristone treatment that depended on endogenous cortisol concentrations.

68. Reduction of hair glucocorticoid levels in an animal model of post-traumatic stress disorder (PTSD)

PTSD results from exposure to a horrific, life-threatening experience. We have developed an animal model of PTSD which involves intense fear-provoking experiences (predator exposure) occurring in conjunction with social instability. Rats exposed to this psychosocial stress (PSS) regimen exhibit changes in physiology and behavior that are comparable to symptoms of people with PTSD (Stress, 11:259–281, 2008). One clinical anomaly, the subject of much debate, is whether basal glucocorticoid (GC) levels are abnormally low in PTSD. There is inconsistent evidence of lower basal GC levels in PTSD, as well as in our animal model of PTSD (Zoladz and Diamond, Neurosci. & Biobehav. Rev., 2013; PNE, 2012). In the current work we addressed this by measuring corticosterone levels in serum, and in a novel approach, fur cortisol of rats exposed to PSS. Adult male rats were immobilized and exposed to a cat twice during a 31 day period of unstable housing followed by fur and basal blood sampling. Rats administered PSS exhibited reduced cortisol levels in fur (1.84 ± 0.22 vs. 3.08 ± 0.45 ng/dl; p p = 0.9). These findings replicate evidence of reduced hair cortisol in people with PTSD (Biol Psychiatry 72: 65–69, 2012), which may be a more reliable measure of baseline GCs than is found in serum in rats and traumatized people.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance.

One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.

An Acute, Double‐Blind, Placebo‐Controlled Cross‐over Study of 320 mg and 640 mg Doses of Bacopa monnieri (CDRI 08) on Multitasking Stress Reactivity and Mood

Little research exists in humans concerning the anxiolytic, antidepressant, sedative, and adaptogenic actions the traditional Ayurvedic medicine Bacopa monnieri (BM) possesses in addition to its documented cognitive-enhancing effects. Preclinical work has identified a number of acute anxiolytic, nootropic, and adaptogenic effects of BM that may also co-occur in humans. The current double-blind, placebo-controlled cross-over study assessed the acute effects of a specific extract of BM (KeenMind® - CDRI 08) in normal healthy participants during completion of a multitasking framework (MTF). Seventeen healthy volunteers completed the MTF, at baseline, then 1 h and 2 h after consuming a placebo, 320 mg BM and 640 mg of BM. Treatments were separated by a 7-day washout with order determined by Latin Square. Outcome measures included cognitive outcomes from the MTF, with mood and salivary cortisol measured before and after each completion of the MTF. Change from baseline scores indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612000834853).

The role of the HPA-axis in understanding psychopathology: cause, consequence, mediator, or moderator?

Human life is not without stressful challenges. These challenges may be even needed to fully exploit one’s potential, and not only include negative experiences in case of the loss of a loved significant other but also be positively colored, such as moving to a new job and trying to meet high-set expectations. We have been endowed with biobehavioral mechanisms to deal with such challenges. One of these mechanisms is the hypothalamus–pituitary–adrenal (HPA)-axis which is a central component of the body’s neuroendocrine response to stress. The hypothalamus secretes corticotropin-releasing hormone (CRH), which in turn stimulates the release of adrenocorticotropic hormone (ACTH) in the anterior pituitary. ACTH in turn stimulates the adrenal cortex to secrete cortisol. Cortisol is known as the major end product of the HPA-axis in humans [1]. Yet, activity of the HPA-axis does not end with the production of cortisol. The HPA-axis is controlled by negative feedback regulation that tends to normalize secretion of cortisol [1]. Elevated cortisol levels reduce ACTH levels as a consequence of negative feedback regulation, followed by a reduction in cortisol levels; in case of reduced cortisol levels, there is less negative feedback regulation at the pituitary, followed by an elevation in ACTH levels [2]. In normal nonstressful situations, cortisol secretion follows a circadian rhythm characterized by high levels in the morning followed by a decrease throughout the rest of the day. Generally, cortisol levels rise in about half an hour after awakening, which is known as the cortisol awakening response (CAR). The CAR is probably related to the

Contagious yawning, social cognition, and arousal: an investigation of the processes underlying shelter dogs’ responses to human yawns

Studies of contagious yawning have reported inconsistent findings regarding whether dogs exhibit this behavior and whether it is mediated by social-cognitive processes or the result of physiological arousal. We investigated why some dogs yawn in response to human yawns; particularly, whether these dogs are exceptional in their ability to understand human social cues or whether they were more physiologically aroused. Sixty shelter dogs were exposed to yawning and nonyawning control stimuli demonstrated by an unfamiliar human. We took salivary cortisol samples before and after testing to determine the role of arousal in yawn contagion. Dogs were tested on the object-choice task to assess their sensitivity for interpreting human social cues. We found that 12 dogs yawned only in response to human yawns (i.e., appeared to exhibit yawn contagion), though contagious yawning at the population level was not observed. Dogs that exhibited yawn contagion did not perform better on the object-choice task than other dogs, but their cortisol levels remained elevated after exposure to human yawning, whereas other dogs had reduced cortisol levels following yawning stimuli relative to their baseline levels. We interpret these findings as showing that human yawning, when presented in a stressful context, can further influence arousal in dogs, which then causes some to yawn. Although the precise social-cognitive mechanisms that underlie contagious yawning in dogs are still unclear, yawning between humans and dogs may involve some communicative function that is modulated by context and arousal.

Effect of combined treatment of selective serotonin reuptake inhibitors plus immunomodulator on circulating cytokines levels in patients with major depressive disorder along 52 weeks of follow up (P4521)

Abstract Major Depressive Disorder (MDD) is a psychiatric illness that commonly displays a deficit of serotonergic neurotransmission in the central nervous system. MDD patients also show alterations in alterations in cortisol and cytokines levels. Those patients are treated with selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to assess the efficacy of the combined treatment with SSRIs plus an immunomodulator -dialyzable leukocyte extract (DLE) - in restoring the balance of both the serotoninergic system and the endocrinoimmune parameters. A total of 34 patients diagnosed with MDD received anti-depressant treatment with SSRIs plus DLE. As control 31 patients received only SSRIs. Proinflammatory cytokines (Th1) IL-1β, IL-2, IFN-γ, anti-inflammatory cytokines (Th2) IL-13, IL-10, and 24-h urine cortisol were determined at weeks (W) 0, 5, 20, 36 and 52 of treatment. The maximum reduction in cortisol levels in SSRIs group was only 30% (W52). By contrast, the treatment with SSRIs plus DLE decreased 53% the cortisol levels from W20. Reduced cortisol in patients treated with SSRI plus DLE correlated with reductions in the concentration of Th2-cytokine and increases in Th1-cytokines at the end of the study. These results suggest that the immune-stimulating action of DLE, in association with the effects of SSRIs, allowed the immune system to balance the ratio of Th1/Th2 cytokines associated and decreased levels of cortisol.

Pitfalls in the Diagnosis of Ectopic Adrenocorticotropic Hormone Syndrome: A Case Report

Ectopic production of adrenocorticotropic hormone by carcinoid tumours is uncommon and covert and occult presentations often hamper its diagnosis. A 27-year-old man was admitted with multiple vertebral bodies collapse related to osteoporosis along with other clinical features consistent with Cushing’s syndrome. Both basal and dynamic laboratory evaluation suggested adrenocorticotropic-dependent Cushing’s syndrome diagnosis, specifically ectopic adrenocorticotropic syndrome. Laboratory testing also showed high serum levels of chromogranin A and urinary 5-hydroxyindoleacetic acid. Pituitary and thoracic-abdominal-pelvic imaging proved to be normal, including the octreoscan. To reduce cortisol levels, and before resorting to adrenalectomy, metyrapone was prescribed but eucortisolism was not achieved. Octreotide therapy reduced plasma adrenocorticotropic hormone and cortisoluria to half although the octreoscan had been negative. As no primitive tumour had been detected, the patient underwent bilateral adrenalectomy. Two years and a half after the diagnosis, an octreoscan detected a lung tumour, which was resected. Pathological analysis revealed an atypical carcinoid tumour and immunohistochemistry was positive for adrenocorticotropic hormone but negative for corticotropin-releasing hormone and chromogranin A. Clinical and biochemical resolution of Cushing’ syndrome followed but chromogranin A levels remained above normal. This case highlights both that, although rare, an exuberant osteoporosis can be the initial presentation of ectopic adrenocorticotropic hormone syndrome and high chromogranin A levels may have other origin than direct tumour production. It also raises the question of prescribing somatostatin agonists in patients whose octreoscan is negative as small tumours may produce false negative results. Moreover, the reduction of hypercortisolism before surgery may improve the surgical outcome and with bilateral adrenalectomy may contribute to the primary tumour growth and detection. doi: http://dx.doi.org/10.4021/jem145w

A Minimal Physiologically Based Model of the HPA Axis under Influence of the Sleep-Wake Cycles

The hypothalamic-pituitary-adrenal axis (also called the HPA or stress axis) exhibits distinct circadian and ultradian rhythms in cortisol release that cannot be explained solely by the feedback loops from cortisol to the control systems in the paraventricular nucleus (PVN) and pituitary gland. The HPA axis is intimately connected with other brain functions. In particular, it is strongly affected by the sleep-wake cycles via direct and indirect effects of the circadian and homeostatic mechanisms. For example, the HPA axis has direct inputs from the master circadian clock in the suprachiasmatic nuclei (SCN), and from the various sleep-wake related neuronal populations, which themselves are under the effects of the circadian and homeostatic processes. In this paper a first step towards a physiologically based mathematical model of the HPA-axis under effects of the sleep-wake cycles is presented. This model accounts for 3 major characteristics of daily cortisol profile in the blood: i) abrupt increase of cortisol concentration in response to awakening, the so-called cortisol-awakening response (CAR); ii) reduced cortisol levels during daytime with underlying ultradian oscillations; and iii) suppression of cortisol release during sleep.

Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial

To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Randomized controlled trial. Clinical research center at an academic medical university. Seventeen women with FHA were randomized either to CBT or observation. CBT versus observation. Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged. In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. NCT01674426.

Osteopathic lymphatic techniques reduces cortisol plasma level in rats after repeated treatments

BackgroundMany reports evidence in humans the positive effect of manipulation, in particular of osteopathic lymphatic techniques in normal as well in pathological conditions. In animals too, lymphatic treatment has been reported to induce changes of lymphatic flux and to mobilize inflammatory mediators thus determining positive effects on the immune system. MethodsTwelve male Wistar rats (weight 180 g) were randomly allocated to control (6 rats) and experimental (6 rats) group. Experimental group rats underwent lymphatic techniques for 10 min each day for 5 consecutive days under gaseous anaesthesia. Control group animals were anaesthetized but did not have lymphatic treatment. Blood samples were collected before and at the end of the experiment period. A complete blood cell count and serum chemistry were determined. TNF-alpha and IL-1 beta were determined in order to evaluate changes in inflammatory response. Cortisol was also determined as indicative of animal stress. The experiment was carried on in August 2011 and was replicated in February 2012. ResultsBlood cell count did not show differences at baseline and at the end of the experiment both in control and in treated rats. Blood serum chemistry was also unchanged. In particular, blood urea nitrogen (BUN) and serum creatinine (expression of renal function), alanine transaminase (ALT) and aspartate transaminase (AST) (indicative of hepatic cell integrity) were normal and did not change after lymphatic treatment. No changes in plasmatic level of cytokines were found after the five-days lymphatic treatment. On the contrary and unexpectedly, cortisol level was significantly reduced in rats that were treated with lymphatic techniques. In untreated rat group cortisol level was, however, minimally increased. These findings were confirmed by the results of the replicated study. ConclusionsThis study demonstrates that repeated lymphatic treatment is a safe procedure. Moreover, lymphatic techniques induce reduction in cortisol level, which may be related to an anti-stress effect.

Combinatorial effects of administration of immunostimulatory compounds in feed and follow‐up administration of triple‐dose SLICE® (emamectin benzoate) on Atlantic salmon, Salmo salar L., infection with Lepeophtheirus salmonis

Several immunostimulatory feed additives have shown the ability to induce protective responses in Atlantic salmon to infection with Lepeophtheirus salmonis. However, even the most encouraging results rarely surpass a 50% protective index in the host. That fact coupled with the well-documented limitations of single-therapy strategies in the effective management of parasitic infections generally make it imperative to identify therapies that can be combined in an integrated pest management approach for sea lice. With this in mind, we hypothesized that immunostimulatory feeds could enhance the protection provided by SLICE® emamectin benzoate (EMB). To test this hypothesis, Atlantic salmon were fed one of two different immunostimulatory feeds (CpG ODN or Aquate®) for c. 7 weeks, challenged with L. salmonis copepodids early within that immunostimulatory feed period and then placed on a triple-dose (150 μg kg(-1) ) feed of SLICE® for 1 week following the completion of the immunostimulatory feeding period. CpG ODN (2 mg kg(-1) ) and the commercial yeast extract (Aquate® 0.2%) inclusion in feeds were able to successfully induce inflammatory gene expression (interleukin-1β) in the head kidneys of infected fish at 13 and 26 days post-exposure (DPE), and 13 DPE, respectively. Lice burdens were lower on fish fed CpG ODN (18%) or Aquate® (19%) diets; however, due to variability, these were not statistically significant over time. Despite no statistically significant reductions in lice numbers, by 33 DPE fish on immunostimulatory feeds had significantly reduced cortisol levels when compared to infected fish on control diet. Cortisol levels in fish receiving an immunostimulatory diet were no different from initial baseline levels prior to infection, whereas the levels in control diet fish were significantly elevated from all other time points. Despite the positive effects on infection of fish fed immunostimulatory feeds, no synergism was observed with follow-up treatment with SLICE® . In fact, highest survival of lice was observed in fish with prior immunostimulation.

Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

Major depressive disorder (MDD) is a psychiatric illness that presents as a deficit of serotonergic neurotransmission in the central nervous system. MDD patients also experience alterations in cortisol and cytokines levels. Treatment with selective serotonin reuptake inhibitors (SSRIs) is the first-line antidepressant regimen for MDD. The aim of this study was to determine the effect of a combination of SSRIs and an immunomodulator—human dialyzable leukocyte extract (hDLE)—on cortisol and cytokines levels. Patients received SSRIs or SSRIs plus hDLE. The proinflammatory cytokines IL-1β, IL-2, and IFN-γ; anti-inflammatory cytokines IL-13 and IL-10; and 24-h urine cortisol were measured at weeks (W) 0, 5, 20, 36, and 52 of treatment. The reduction in cortisol levels in the SSRI-treated group was 30% until W52, in contrast, the combined treatment induced a 54% decrease at W36. The decline in cortisol in patients who were treated with SSRI plus hDLE correlated with reduction of anti-inflammatory cytokines and increases levels of proinflammatory cytokines at the study conclusion. These results suggest that the immune-stimulating activity of hDLE, in combination with SSRIs, restored the pro- and anti-inflammatory cytokine balance and cortisol levels in depressed patients versus those who were given SSRIs alone.

Effects of Cortisol on Physical and Psychological Aspects of the Body and Effective Ways by Which One Can Reduce Stress

EFFECTS OF CORTISOL ON PHYSICAL AND PSYCHOLOGICAL ASPECTS OF THE BODY AND EFFECTIVE WAYS BY WHICH ONE CAN REDUCE STRESS Preethi Kandhalu B S J O ver the past years, reports of increased stress levels in millennials have been on the rise; Stress in America, a study, from the American Psychological Association found “half of all millennials are so stressed out that they can’t sleep at night, and 39 percent of millennials have stress levels that have increased in the past year” (Yandoli, 2013) and “On a 10-point scale, Americans ages 18-33 reported an average stress level of 5.4 compared to the national average of 4.9” (Kingkade, 2013). Consequently, there are a plethora of suggestions regarding ways to reduce stress – common tips include keeping a positive attitude, exercising and eating healthy (WebMD). A popular website also indicates that eating berries help combat stress since “Blueberries are naturally rich in vitamin C, which helps fight increased levels of cortisol, a stress hormone” 1 (Oz, 2010). Unfortunately, for most people, it is difficult to evaluate whether such tips are effective stress reducers. The aim of this article is to explain why stress exists. The cortisol hormone, i.e. “stress hormone” that’s secreted by the Hypothalamic-Pituitary-Adrenal (HPA) affects our body in both physical and mental ways that can be detrimental to our overall health. Some of the effects of stress can be due to our genes, while some effects can be due to external environmental factors. However, there do exist effective ways by which one can reduce cortisol levels. I n order to understand why we feel stressed, it is important to understand the mechanism of the Hypothalamic-Pituitary-Adrenal (HPA) axis, an axis (“Hypothalamic–pituitary–adrenal axis”). In the first step of the process, the hypothalamus contains neuroendocrine neurons that synthesize proteins, which act as hormones when released. While some hormones target distant tissues, some hormones – including vasopressin and corticotropin releasing hormone (CRH) – are released in the blood circulation of the axis for delivery to the pituitary gland. The CRH is received by the anterior pituitary gland, which in turn secretes Adrenocorticotropic Hormone (ACTH) within the blood circulation of the axis. ACTH further Fig 1. HPA Mechanism acts on the two of the three zones of the adrenal gland – zona fasciculate and the zona reticularis – this action leads to the secretion of glucocorticoids (which mainly consists of cortisol in humans) among other hormones (Mitrovic). Also, 90% of the cortisol is eventually “S ome ailments caused by increased levels in cortisol include a suppressed immune system , insomnia , severe mood swings , depression and severe hypotension ” along our brain that secretes cortisol. The hormones produced by the hypothalamus results in a cascade of events down the HPA axis which ultimately leads to the secretion of cortisol from the adrenal gland bound by proteins, whereas 10% of the free cortisol is unbound, and therefore biologically active – this free cortisol creates a negative feedback loop whereby it binds to hypothalamus and the pituitary gland to inhibit secretion of CRH and ACTH (Mitrovic). Scientific experiments done to determine correlation between Vitamin E and C levels, and cortisol levels actually suggest that cortisol production did not change with different concentrations of Vitamin E and C. In other words, blueberries do not fight increased levels of cortisol. (Montalvo, Diaz, Galdames, Andres & Larrain, 2011) 14 • B erkeley S cientific J ournal • S tress • F all 2013 V olume 18 • I ssue 1

Pitfalls in the Diagnosis of Ectopic Adrenocorticotropic Hormone Syndrome: A Case Report

Ectopic production of adrenocorticotropic hormone by carcinoid tumours is uncommon and covert and occult presentations often hamper its diagnosis. A 27-year-old man was admitted with multiple vertebral bodies collapse related to osteoporosis along with other clinical features consistent with Cushing’s syndrome. Both basal and dynamic laboratory evaluation suggested adrenocorticotropic-dependent Cushing’s syndrome diagnosis, specifically ectopic adrenocorticotropic syndrome. Laboratory testing also showed high serum levels of chromogranin A and urinary 5-hydroxyindoleacetic acid. Pituitary and thoracic-abdominal-pelvic imaging proved to be normal, including the octreoscan. To reduce cortisol levels, and before resorting to adrenalectomy, metyrapone was prescribed but eucortisolism was not achieved. Octreotide therapy reduced plasma adrenocorticotropic hormone and cortisoluria to half although the octreoscan had been negative. As no primitive tumour had been detected, the patient underwent bilateral adrenalectomy. Two years and a half after the diagnosis, an octreoscan detected a lung tumour, which was resected. Pathological analysis revealed an atypical carcinoid tumour and immunohistochemistry was positive for adrenocorticotropic hormone but negative for corticotropin-releasing hormone and chromogranin A. Clinical and biochemical resolution of Cushing’ syndrome followed but chromogranin A levels remained above normal. This case highlights both that, although rare, an exuberant osteoporosis can be the initial presentation of ectopic adrenocorticotropic hormone syndrome and high chromogranin A levels may have other origin than direct tumour production. It also raises the question of prescribing somatostatin agonists in patients whose octreoscan is negative as small tumours may produce false negative results. Moreover, the reduction of hypercortisolism before surgery may improve the surgical outcome and with bilateral adrenalectomy may contribute to the primary tumour growth and detection. J Endocrinol Metab. 2013;3(1-2):29-37 doi: https://doi.org/10.4021/jem145w

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 trait measures also presented greater placebo-induced activation of μ-opioid neurotransmission in the subgenual and dorsal anterior cingulate cortex (ACC), orbitofrontal cortex, insula, nucleus accumbens, amygdala and periaqueductal gray (PAG). Endogenous opioid release in the dorsal ACC and PAG was positively correlated with placebo-induced reductions in pain ratings. Significant reductions in cortisol levels were observed during placebo administration and were positively correlated with decreases in pain ratings, μ-opioid system activation in the dorsal ACC and PAG, and as a trend, negatively with NEO Angry Hostility scores. Our results show that personality traits explain a substantial proportion of the variance in placebo analgesic responses and are further associated with activations in endogenous opioid neurotransmission, and as a trend cortisol plasma levels. This initial data, if replicated in larger sample, suggest that simple trait measures easily deployable in the field could be utilized to reduce variability in clinical trials, but may also point to measures of individual resiliency in the face of aversive stimuli such as persistent pain and potentially other stressors.

Effect of micronutrient supplementation around calving on the plasma cortisol levels of Murrah buffaloes and Sahiwal and Karan Fries cows

Micronutrients when fed around peripartum may reduce the stress induced by cortisol. With this objective, 24 Sahiwal (SW) and 24 Karan Fries (KF) cows and 24 Murrah (Mu) buffaloes were taken and divided into four groups of six each. Vitamin E (VE), zinc (Zn) and copper were supplemented from 30 days pre- to 30 days postcalving in groups 1, 2 and 3. Animals without supplementation served as control. Blood sampling was done on days 30, 15, 7 and 3 precalving; at calving; and on days 3, 7, 15 and 30 postcalving. Plasma cortisol levels were measured by ELISA. Supplementation of VE and Zn significantly (P<0.05) reduced plasma cortisol levels at calving and at 30 days postcalving. KF cows exhibited best results with VE, whereas SW cows and Mu buffaloes responded best to Zn. Copper increased the peripartum cortisol levels. Reduction in cortisol levels may help in keeping the animal healthy and stronger to fight immuno-suppression generally observed around the period of peripartum.

Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing’s syndrome

The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing's syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing's syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels < 3 and < 1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.

Sporadic fatal insomnia with clinical, laboratory, and genetic findings

A 75-year-old man presented with a three-year history of progressively worsening insomnia and dementia. His mother and older sister had similar disorders. On initial examination, he was awake, apathetic, and disoriented but had no focal neurological deficits. Electroencephalography showed diffuse background slowing with neither periodic discharge nor sleeping activity. A single-photon emission CT scan showed significantly reduced cerebral perfusion in bilateral thalami, basal ganglia, and limbic cortices. In the late stage of his illness, he developed sphincter dysfunction. Laboratory studies showed increased T-lymphocytes and B-lymphocytes and reduced cortisol level. Cerebrospinal fluid 14-3-3 protein was absent. Genetic evaluations failed to show the aspartate to asparagine point mutation at codon 178 but disclosed an asparagine to serine substitution at codon 171 in one allele and a deletion of 24 base pairs in the other allele in the human prion protein gene. These findings led to a diagnosis of sporadic fatal insomnia, which is a recently described prion disease.

The consumption of a Jerte Valley cherry product in humans enhances mood, and increases 5-hydroxyindoleacetic acid but reduces cortisol levels in urine

PurposeJerte Valley cherries contain high levels of tryptophan, serotonin, and melatonin. These molecules have been shown to be involved in mood regulation. It has been suggested that a complex inter-relationship between brain serotonin, circulating levels of cortisol (the major stress hormone), and the hypothalamus–pituitary–adrenal axis exists in the regulation of stress responses, where cortisol and serotonin act as markers of mood disturbances. Moreover there is growing evidence that altered HPA activity is associated with various age-related pathologies. The present study evaluated the effect of the ingestion of a Jerte Valley cherry‐based product, compared to a placebo product, on urine cortisol and 5-hydroxyindoleacetic acid (5-HIAA) levels, and on mood in young, middle-aged, and elderly participants. MethodsCortisol and 5-HIAA acid levels were measured by commercial enzyme-linked immunosorbent assay kits. The mood state profile was analysed using a visual analogue scale and the state–trait anxiety inventory. ResultsOur findings showed that the ingestion of the Jerte Valley cherry product decreased urinary cortisol and increased urinary 5-HIAA levels in all the experimental groups. Moreover, the cherry product was able to lessen anxiety status in the middle-aged and elderly participants, and enhanced subjective mood parameters, particularly family relationships in young participants, and frame of mind and fitness in both middle-aged and elderly subjects. ConclusionsThe consumption of the Jerte Valley cherry product may protect against stress and act as a mood enhancer by increasing serotonin availability to the organism, particularly with advancing age.