776 research outputs found

    Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

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    The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA) axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB) display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment

    Sex Differences in the Impact of Obstructive Sleep Apnea on Glucose Metabolism

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    Objectives: Obstructive sleep apnea (OSA) is more prevalent in men and is an independent risk factor for type 2 diabetes. We aimed to determine if there are sex differences in the impact of OSA on glucose metabolism in nondiabetic overweight and obese adults.Methods: One hundred and forty-five men and women (age 33.4 ± 0.6, BMI 37.2 ± 0.7, 70.3% blacks) from the community underwent in-laboratory polysomnography. Severity of OSA was assessed by the apnea-hypopnea index (AHI). Glucose tolerance was assessed using fasting glucose, 1-h glucose, 2-h glucose and the area under the curve (AUC) during the 2-h oral glucose tolerance test (OGTT). Fasting insulin resistance was assessed by HOMA-IR, and insulin sensitivity during the OGTT was assessed by the Matsuda Index. Pancreatic beta-cell function was assessed by fasting HOMA-%B and by AUCinsulin/glucose, insulinogenic index, and oral disposition index (DIoral) during the OGTT. All comparisons were adjusted for age, BMI, race and severity of OSA.Results: There were no significant demographic differences between men and women without OSA. Men and women with OSA were similar in age, BMI, and severity of OSA, but there were more black women with OSA. Compared to women with OSA, men with OSA had significantly higher fasting glucose, 1-h glucose levels, AUCglucose, and AUC for insulin secretion rate (AUCISR) but similar 2-h glucose levels. These differences persisted in adjusted analyses. Men with OSA secreted significantly more insulin than women with OSA in order to achieve similar glucose levels. Men with OSA had significantly worse beta cell function as measured by the DIoral than women with OSA. In contrast, there were no significant sex differences in measures of glucose tolerance and beta-cell function in participants without OSA.Conclusion: Men with OSA secreted more insulin compared to women with OSA in order to maintain glucose homeostasis. The adverse impact of OSA on beta-cell responsiveness was larger in men, which may result in an overall greater risk of type 2 diabetes compared to women

    Stimulatory Effect of Morning Bright Light on Reproductive Hormones and Ovulation: Results of a Controlled Crossover Trial

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    OBJECTIVES: Studies have shown a shortening of the menstrual cycle following light exposure in women with abnormally long menstrual cycles or with winter depression, suggesting that artificial light can influence reproductive hormones and ovulation. The study was designed to investigate this possibility. DESIGN: Placebo-controlled, crossover, counterbalanced order. SETTING: Medical centres and participants' homes in Novosibirsk (55°N), Russia. PARTICIPANTS: Twenty-two women, aged 19–37 years, with baseline menstrual cycle length 28.1–37.8 d and no clinically evident endocrine abnormalities completed the study. The study lasted for two menstrual cycles separated by at least one off-protocol cycle. INTERVENTIONS: During one experimental cycle, bright light was administered at home for 1 wk with a light box emitting white light at 4,300 lux at 41 cm for 45 min shortly after awakening. During the other experimental cycle, dim light was <100 lux at 41 cm with a one-tube fluorescent source. OUTCOME MEASURES: Blood samples and ultrasound scans were obtained in the afternoon before and after the week of light exposure, on day ∼7 and 14 after menstruation onset. Further ultrasound scans after day 14 documented ovulation. Serum was assayed for thyroid-stimulating hormone (TSH), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2). RESULTS: Concentrations of PRL, LH, and FSH were significantly increased with bright versus dim light exposure, as was follicle size (ANOVA, intervention × day, p = 0.0043, 0.014, 0.049, and 0.042, respectively). The number of ovulatory cycles increased after exposure to bright compared to dim light (12 versus 6 cycles, Wilcoxon tied p = 0.034). CONCLUSIONS: Morning exposure to bright light in the follicular phase of the menstrual cycle stimulates the secretion of hypophyseal reproductive hormones, promotes ovary follicle growth, and increases ovulation rates in women with slightly lengthened menstrual cycles. This might be a promising method to overcome infertility

    The independent effects of match location, match result and the quality of opposition on subjective wellbeing in under 23 soccer players: a case study

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    This study examined if subjective wellbeing in soccer players was affected by match location, match result and opposition quality before a match (PRE), 1 day after (POST-1), and 3 days after a match (POST-3). Eleven professional male soccer players from the under 23 squad playing in the Premier League 2 division completed a wellbeing questionnaire before and after 17 matches. Match training load (session-rating perceived exertion) was not different, regardless of the location, result, or quality of opposition faced (P > 0.05). Subjective wellbeing was not different at PRE (P > 0.05); however, at POST-1 and POST-3, stress and mood were ≥20% lower after playing away from home or losing (P < 0.05). Stress, mood and sleep were ≥12% worse after playing against a higher-level opposition at POST-1. Coaches need to be aware that match location, match result and the quality of the opposition can influence post-match wellbeing, irrespective of match load

    HPA axis activity in patients with panic disorder: review and synthesis of four studies

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    Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis may play a role in panic disorder. HPA studies in patients with panic disorder, however, have produced inconsistent results. Seeking to understand the inconsistencies, we reexamined endocrine data from four studies of patients with panic disorder, in light of animal data highlighting the salience of novelty, control, and social support to HPA axis activity. Patients with panic disorder were studied (1) at rest over a full circadian cycle, (2) before and after activation by a panicogenic respiratory stimulant (doxapram) that does not directly stimulate the HPA axis, and (3) before and after a cholecystokinin B (CCK-B) agonist that is panicogenic and does directly stimulate the HPA axis. Patients with panic disorder had elevated overnight cortisol levels, which correlated with sleep disruption. ACTH and cortisol levels were higher in a challenge paradigm (doxapram) than in a resting state study, and paradigm-related ACTH secretion was exaggerated in patients with panic disorder. Panic itself could be elicited without HPA axis activation. Patients with panic disorder showed an exaggerated ACTH response to pentagastrin stimulation, but this response was normalized by prior exposure to the experimental context or psychological preparation to reduce novelty and enhance sense of control. Novelty is one of a number of contextual cues known from animal work to activate the HPA axis. The HPA axis abnormalities seen in patients with panic disorder in the four experiments reviewed here might all be due to exaggerated HPA axis reactivity to novelty cues. Most of the published panic/HPA literature is consistent with the hypothesis that HPA axis dysregulation in panic is due to hypersensitivity to contextual cues. This hypothesis requires experimental testing. Depression and Anxiety 24:66–76, 2007. Published 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55906/1/20220_ftp.pd

    Rai1 frees mice from the repression of active wake behaviors by light.

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    Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka 'masking') mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output

    Is physiological glucocorticoid replacement important in children?

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    Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics
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