A Kales

Pennsylvania State University, University Park, MD, United States

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Publications (221)1748.71 Total impact

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    ABSTRACT: The aim of this study was to clarify the nature of the sleep abnormalities (excessive daytime sleepiness [EDS] and rapid eye movement [REM] sleep alterations) in Prader-Willi, Syndrome (PWS). Eight PWS patients, 15 normal, 16 narcoleptic, and 16 obese subjects were recorded in the sleep laboratory, both during daytime and nighttime. A principal-finding was that EDS in PWS was associated with an increased amount and depth of sleep. In PWS patients with EDS, compared to those PWS patients without EDS or the narcoleptic. obese, and normal groups, there were significant decreases in wakefulness and increases in percentage of sleep time (ST) and slow-wave sleep (SWS) both during daytime and nighttime testing. Also, in the adult PWS subjects (n=6), in contrast to normal and narcoleptic subjects, intensity of EDS was correlated with increased nocturnal percentage of ST and SWS and % SWS was positively correlated with % ST (both during daytime and nighttime testing). Another principal finding was that in PWS patients with EDS or shortened nocturnal REM latencies showed a significantly increased number of REM periods, and a decreased average REM interval between REM periods compared to PWS patients with nonshortened nocturnal REM latencies or to the three control groups. Our data suggest that EDS and REM abnormalities in PWS are not manifestations of a narcoleptic-type syndrome or consequences of obesity. We propose that generalized 24-hour hypoarousal is the primary mechanism underlying the sleep abnormalities in PWS patients.
    International Journal of Neuroscience. 07/2009; 87(3-4).
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    ABSTRACT: Excessive daytime sleepiness (EDS) is commonly considered a cardinal sign of sleep apnea; however, the mechanism underlying the association is unclear. The purpose of this study was to assess the association between the complaint of EDS and sleep apnea, considering a wide range of possible risk factors in a population sample. We examined this question in the Penn State cohort (a random sample of 16,583 men and women from central Pennsylvania, ranging in age from 20 to 100 yr). A random subset of this cohort (n = 1,741) was further evaluated for one night in the sleep laboratory. The main measure was a complaint of EDS. The final logistic regression model indicated depression was the most significant risk factor for EDS followed by body mass index, age, typical sleep duration, diabetes, smoking, and finally sleep apnea. The strength of the association with EDS decreased with increasing age, whereas the association of depression with EDS was stronger in the young. EDS is more prevalent in the young (<30 yr), suggesting the presence of unmet sleep needs and depression, and in the very old (>75 yr), suggesting increasing medical illness and health problems. EDS was associated with a reduced report of typical sleep duration without any association with objective polysomnographic measures. It appears that the presence of EDS is more strongly associated with depression and metabolic factors than with sleep-disordered breathing or sleep disruption per se. Our findings suggest that patients with a complaint of EDS should be thoroughly assessed for depression and obesity/diabetes independent of whether sleep-disordered breathing is present.
    Journal of Clinical Endocrinology &amp Metabolism 09/2005; 90(8):4510-5. · 6.43 Impact Factor
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    ABSTRACT: Total sleep restriction in humans is associated with increased daytime sleepiness, decreased performance, and hormonal/metabolic disturbances. The effects of mild chronic sleep restriction that mimic real life are not known. To assess the effects of modest sleep restriction from 8 to 6 h/night for 1 wk, 25 young, healthy, normal sleepers (12 men and 13 women) were studied for 12 consecutive nights in the sleep laboratory. After 1 wk of sleep restriction, although subjects' nighttime sleep was deeper, subjects were significantly sleepier (multiple sleep latency test) and performed worse in four primary variables of psychomotor vigilance test (both P < 0.01). Furthermore, 24-h secretion of IL-6 was increased by 0.8 +/- 0.3 pg/ml (P < 0.05) in both sexes, whereas TNFalpha was increased only in men. Also, the peak cortisol secretion was lower after sleep restriction than at baseline, and this difference was stronger in men (55.18 +/- 24.83 nmol/liter; P < 0.05) than in women (35.87 +/- 24.83 nmol/liter; P < 0.16). We conclude that in young men and women, modest sleep loss is associated with significant sleepiness, impairment of psychomotor performance, and increased secretion of proinflammatory cytokines. Given the potential association of these behavioral and physical alterations with health, well-being, and public safety, the idea that sleep or parts of it are optional should be regarded with caution.
    Journal of Clinical Endocrinology &amp Metabolism 06/2004; 89(5):2119-26. · 6.43 Impact Factor
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    ABSTRACT: Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the neuroendocrine system. A symposium was organized in March 2001 to explore the possibility of an association between neuroendocrine dysfunction and CFS, with special emphasis on the interactions between neuroendocrine dysfunction and other abnormalities noted in the immune and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.
    NeuroImmunoModulation 02/2004; 11(2):65-74. · 1.84 Impact Factor
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    ABSTRACT: IL-6 and TNF alpha secretion is increased by sleep loss or restriction. IL-6 secretion progressively increases with age, yet its association with decreased quality and quantity of sleep in old adults is unknown. This study examined the alteration of 24-h secretory pattern of IL-6, TNF alpha, and cortisol in 15 young and 13 old normal sleepers who were recorded in the sleep laboratory for four consecutive nights. Serial 24-h plasma measures of IL-6, TNF alpha, and cortisol were obtained during the fourth day, and daytime sleepiness was assessed with the multiple sleep latency test. Old adults, compared with young subjects, slept poorly at night (wake time and percentage stage 1 sleep were increased, whereas their percentage slow wave sleep and percentage sleep time were decreased, P < 0.05). Accordingly, their daytime sleep latency was longer than in young adults (P < 0.05). The mean 24-h IL-6 and cortisol levels were significantly higher in old than young adults (P < 0.05). In both groups, IL-6 and cortisol plasma concentrations were positively associated with total wake time, with a stronger association of IL-6 and cortisol with total wake time in the older individuals (P < 0.05); their combined effect was additive. IL-6 had a negative association with rapid eye movement (REM) sleep only in the young (P < 0.05), but cortisol was associated negatively with REM sleep both in the young and old, with a stronger effect in the young. We conclude that in healthy adults, age-related alterations in nocturnal wake time and daytime sleepiness are associated with elevations of both plasma IL-6 and cortisol concentrations, but REM sleep decline with age is primarily associated with cortisol increases.
    Journal of Clinical Endocrinology &amp Metabolism 05/2003; 88(5):2087-95. · 6.43 Impact Factor
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    ABSTRACT: Establish the association between insomnia and various physical and mental health symptoms as well as objective measures of sleep disturbance while controlling for age, gender and BMI in a large random sample of the general public. A subsample (N=1741) was selected for a single-night sleep laboratory evaluation from a larger random sample (N=16,583) of the general public (20-100 years old). The prevalence of insomnia was 7.5% and difficulty sleeping an additional 22.4%. The complaints were more frequent in women and in non-Caucasian minorities. A multivariate logistic regression analysis indicated that depression was the single strongest factor followed by female gender associated with either insomnia or difficulty sleeping. Minority status and a history of colitis, hypertension and anemia were also associated, but to a lesser degree. The final model did not include age, BMI as well as any of the sleep laboratory findings. These findings support the conclusion that mental health variables have the primary independent association with a complaint of insomnia. Other factors including minorities and hypertension are also independently associated, though to a lesser degree. Other primary sleep disorders, e.g., sleep apnea, do not seem to play a major role in insomnia. These findings underscore the fact that insomnia is a symptom associated with a wide variety of mental and physical health problems requiring a proper psychiatric and medical management.
    Journal of Psychosomatic Research 08/2002; 53(1):589-92. · 3.27 Impact Factor
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    ABSTRACT: Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by difficulty falling or staying asleep at night and increased fatigue during the day. Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are fatigue-inducing cytokines, and the daytime secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. We hypothesize that the poor quality of insomniacs' sleep is associated with a hypersecretion of these 2 cytokines during the daytime, which, in turn, correlates with the fatigue experienced by these patients. Eleven young insomniacs (6 men and 5 women) and 11 (8 men and 3 women) age- and body mass index (BMI)-matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for 4 consecutive nights and serial 24-hour plasma measures of IL-6 and TNF were obtained during the 4th day. Insomniacs compared to controls slept poorly (sleep latency and wake were increased, whereas percentage sleep time was decreased during baseline nights, all P <.05). The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, the difference in the change (increase) of IL-6 plasma levels from midafternoon (2 PM) to evening (9 PM) between insomniacs and controls was significant (P <.01). Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from nighttime (4 AM) to evening (7 PM) in insomniacs compared to controls (P <.05). Also, while TNF secretion in controls showed a distinct circadian rhythm with a peak close and prior to the offset of sleep (P <.05), such a rhythm was not present in insomniacs. Finally, daytime secretion of TNF in insomniacs was characterized by a regular rhythm of 4 hours (P <.05); such a distinct periodicity was not present in controls. We conclude that chronic insomnia is associated with a shift of IL-6 and TNF secretion from nighttime to daytime, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 and TNF secretion, combined with a 24-hour hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty falling asleep.
    Metabolism 07/2002; 51(7):887-92. · 3.10 Impact Factor
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    ABSTRACT: Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-h ACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pM, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 nM, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss, which is usually associated with no change or decrease in cortisol secretion or a circadian disturbance. Chronic activation of the hypothalamic-pituitary-adrenal axis in insomnia suggests that insomniacs are at risk not only for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeutic goal in insomnia should be to decrease the overall level of physiologic and emotional arousal, and not just to improve the nighttime sleep.
    Journal of Clinical Endocrinology &amp Metabolism 08/2001; 86(8):3787-94. · 6.43 Impact Factor
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    ABSTRACT: The prevalence of insomnia associated with emotional stress increases markedly in middle-age. Both the top and end hormones of the hypothalamic-pituitary-adrenal axis, i.e. CRH and glucocorticoids, stimulate arousal/wakefulness and inhibit slow wave (deep) sleep in experimental animals and man. The objective of this study was to test the hypothesis that middle-age is characterized by increased sensitivity to the sleep-disturbing effects of the hypothalamic-pituitary-adrenal axis. We studied 12 healthy middle-aged (45.1 +/- 4.9) and 12 healthy young (22.7 +/- 2.8) men by monitoring their sleep by polysomnography for 4 consecutive nights, including in tandem 1 adaptation and 2 baseline nights and a night during which we administered equipotent doses of ovine CRH (1 microg/kg, iv bolus) 10 min after sleep onset. Analyses included comparisons within and between groups using multiple ANOVA and regression analysis. Although both middle-aged and young men responded to CRH with similar elevations of ACTH and cortisol, the former had significantly more wakefulness and suppression of slow wave sleep compared with baseline sleep; in contrast, the latter showed no change. Also, comparison of the change in sleep patterns from baseline to the CRH night in the young men to the respective change observed in middle-aged men showed that middle-age was associated with significantly higher wakefulness and significantly greater decrease in slow wave sleep than in young age. We conclude that middle-aged men show increased vulnerability of sleep to stress hormones, possibly resulting in impairments in the quality of sleep during periods of stress. We suggest that changes in sleep physiology associated with middle-age play a significant role in the marked increase of prevalence of insomnia in middle-age.
    Journal of Clinical Endocrinology &amp Metabolism 05/2001; 86(4):1489-95. · 6.43 Impact Factor
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    ABSTRACT: The prevalence of sleep-disordered breathing has not been well studied in women, especially in terms of the effects of age, body mass index (BMI), and menopause. We evaluated this question using a two-phase random sample from the general population. In Phase I, 12,219 women and 4,364 men ranging in age from 20 to 100 yr were interviewed; and in Phase II, 1,000 women and 741 men of the Phase I subjects were selected for one night of sleep laboratory evaluation. The results of our study indicated that, for clinically defined sleep apnea (apnea/hypopnea index > or = 10 and daytime symptoms), men had a prevalence of 3.9% and women 1.2%, resulting in an overall ratio of sleep apnea for men to women of 3.3:1 (p = 0.0006). The prevalence of sleep apnea was quite low in premenopausal women (0.6%) as well as postmenopausal women with hormone replacement therapy (HRT) (0.5%). Further, in these women the presence of sleep apnea appeared to be associated exclusively with obesity (BMI > or = 32.3 kg/m2). Postmenopausal women without HRT had a prevalence of sleep apnea that was significantly higher than the prevalence in premenopausal women with HRT (2.7 versus 0.6%, p = 0.02) and was more similar to the prevalence in men (3.9%), although it remained significantly less when controlling for age and BMI (p = 0.001). These data combined indicate that menopause is a significant risk factor for sleep apnea in women and that hormone replacement appears to be associated with reduced risk.
    American Journal of Respiratory and Critical Care Medicine 03/2001; 163(3 Pt 1):608-13. · 11.04 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of premenopausal women, characterized by chronic hyperandrogenism, oligoanovulation, and insulin resistance. Obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) are strongly associated with insulin resistance and hypercytokinemia, independently of obesity. We hypothesized that women with PCOS are at risk for OSA and EDS. Fifty-three women with PCOS (age range, 16-45 yr) and 452 control premenopausal women (age range, 20-42), from a general randomized sample for the assessment of prevalence of OSA, were evaluated in the sleep laboratory for 1 night. In addition, women with PCOS were tested for plasma free and weakly bound testosterone, total testosterone, and fasting blood glucose and insulin concentrations. In this study, PCOS patients were 30 times more likely to suffer from sleep disordered breathing (SDB) than the controls [odds ratio = 30.6, 95% confidence interval (7.2-139.4)]. Nine of the PCOS patients (17.0%) were recommended treatment for SDB, in contrast with only 3 (0.6%) of the control group (P < 0.001). In addition, PCOS patients reported more frequent daytime sleepiness than the controls (80.4% vs. 27.0%, respectively; P < 0.001). PCOS patients who were recommended treatment for SDB, compared with those who were not, had significantly higher fasting plasma insulin levels (306.48 +/- 52.39 vs. 176.71 +/- 18.13 pmol/L, P < 0.01) and a lower glucose-to-insulin ratio (0.02 +/- 0.00 vs. 0.04 +/- 0.00, P < 0.05). Plasma free and total testosterone and fasting blood glucose concentrations were not different between the two groups of PCOS women. Our data indicate that SDB and EDS are markedly and significantly more frequent in PCOS women than in premenopausal controls. Also, insulin resistance is a stronger risk factor than is body mass index or testosterone for SDB in PCOS women. These data support our proposal that, independently of gender, sleep apnea might be a manifestation of an endocrine/metabolic abnormality in which insulin resistance plays a principal role.
    Journal of Clinical Endocrinology &amp Metabolism 02/2001; 86(2):517-20. · 6.43 Impact Factor
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    ABSTRACT: Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-alpha and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.
    Journal of Clinical Endocrinology &amp Metabolism 03/2000; 85(3):1151-8. · 6.43 Impact Factor
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    ABSTRACT: To our knowledge, the association between sleep-disordered breathing (SDB) and hypertension has not been evaluated in subjects from the general population with a wide age range while adjusting for the possible confounding factors of age, body mass index, sex, menopause and use of hormone replacement therapy, race, alcohol use, and smoking. In the first phase of this study, we interviewed 4364 men and 12,219 women, aged 20 to 100 years. In the second phase of this study, 741 men and 1000 women, previously interviewed, were selected based on the presence of risk factors for SDB (snoring, daytime sleepiness, obesity, hypertension, and, for women, menopause). Each subject selected for the second phase of the study provided a comprehensive history, underwent a physical examination, and was evaluated for 1 night in the sleep laboratory. In terms of severity of SDB, 4 groups were identified: moderate or severe (obstructive apnea/hypopnea index > or =15.0), mild (snoring and an obstructive apnea/hypopnea index of 0.1-14.9), snoring, and no SDB, the control group. Sleep-disordered breathing was independently associated with hypertension when potential confounders were controlled for in the logistic regression analysis. The strength of this association decreased with age and was proportional to the severity of SDB. In the best-fitted model, neither sex nor menopause changed the relationship between hypertension and SDB. In the results of this study, SDB, even snoring, was independently associated with hypertension in both men and women. This relationship was strongest in young subjects, especially those of normal weight, a finding that is consistent with previous findings that SDB is more severe in young individuals.
    Archives of Internal Medicine 01/2000; 160(15):2289-95. · 11.46 Impact Factor
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    ABSTRACT: The differential diagnosis of primary (idiopathic) vs. psychiatric hypersomnia is challenging because of the lack of specific clinical or laboratory criteria differentiating these two disorders and the frequent comorbidity of mental disorders in patients with primary hypersomnia. The aim of this study was to assess whether polysomnography aids in the differential diagnosis of these two disorders. After excluding patients taking medication and those with an additional diagnosis of sleep-disordered breathing, we compared the nocturnal and daytime sleep of 82 consecutive patients with a diagnosis of either primary hypersomnia (N = 59) or psychiatric hypersomnia (N = 23) and normal control subjects (N = 50). During nocturnal sleep, patients with psychiatric hypersomnia showed significantly higher sleep latency, wake time after sleep onset, and total wake time and a significantly lower percentage of sleep time than patients with primary hypersomnia and control subjects (p < .05). In addition, the daytime sleep of patients with psychiatric hypersomnia was significantly higher in terms of sleep latency, total wake time, and percentage of light (stage 1) sleep and lower in terms of percentage of sleep time and stage 2 sleep than in patients with primary hypersomnia and control subjects (p < .05). The daytime sleep of patients with primary hypersomnia as compared with that of control subjects was characterized by lower sleep latency and total wake time and a higher percentage of sleep time (p < .05). Finally, a sleep latency of less than 10 minutes or a sleep time percentage greater than 70% in either of the two daytime naps was associated with a sensitivity of 78.0% and a specificity of 95.7%. Our findings indicate that psychiatric hypersomnia is a disorder of hyperarousal, whereas primary hypersomnia is a disorder of hypoarousal. Polysomnographic measures may provide useful information in the differential diagnosis and treatment of these two disorders.
    Psychosomatic Medicine 01/2000; 62(2):220-6. · 4.08 Impact Factor
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    ABSTRACT: Patients with pathologically increased daytime sleepiness and fatigue have elevated levels of circulating interleukin-6 (IL-6). The latter is an inflammatory cytokine, which causes sickness manifestations, including somnolence and fatigue, and activation of the hypothalamic-pituitary-adrenal axis. In this study, we examined: 1) the relation between serial measurements of plasma IL-6 and quantity and depth of sleep, evaluated by polysomnography; and 2) the effects of sleep deprivation on the nyctohemeral pattern of IL-6 secretion. Eight healthy young male volunteers were sampled for 24 h twice, at the baseline state, after a normal night's sleep and after total overnight sleep deprivation. At the baseline state, IL-6 was secreted in a biphasic circadian pattern with two nadirs at 0800 and 2100 and two zeniths at 1900 and 0500 (P < 0.01). The baseline amount of sleep correlated negatively with the overall daytime secretion of the cytokine (P < 0.05). Also, depth of sleep at baseline correlated negatively with the postdeprivation increase of daytime secretion of IL-6 (P < 0.05). Sleep deprivation changed the temporal pattern of circadian IL-6 secretion but not the overall amount. Indeed, during the post-deprivation period, the mean daytime (0800-2200 h) levels of IL-6 were significantly higher (P < 0.05), whereas the nighttime (2200-0600 h) levels were lower than the predeprivation values. Thus, sleep-deprived subjects had daytime oversecretion and nighttime under-secretion of IL-6; the former might be responsible for their daylong somnolence and fatigue, the latter for the better quality (depth) of their sleep. These data suggest that a good night's sleep is associated with decreased daytime secretion of IL-6 and a good sense of well-being and that good sleep is associated with decreased exposure of tissues to the proinflammatory and potentially detrimental actions of IL-6. Sleep deprivation increases daytime IL-6 and causes somnolence and fatigue during the next day, whereas postdeprivation decreases nighttime IL-6 and is associated with deeper sleep.
    Journal of Clinical Endocrinology &amp Metabolism 09/1999; 84(8):2603-7. · 6.43 Impact Factor
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    ABSTRACT: Although several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis. After four consecutive nights in the Sleep Laboratory, 10 healthy young men were totally deprived of sleep during the fifth night, and then allowed to sleep again on nights six and seven. Twenty-four hour blood sampling was performed serially every 30 minutes on the fourth day, immediately following the previous night of sleep and on the sixth day, immediately after sleep deprivation. Eight-hour sleep laboratory recording, including electroencephologram, electro-oculogram and electromyogram. Plasma cortisol and GH levels using specific immunoassay techniques. Mean plasma and time-integrated (AUC) cortisol levels were lower during the postdeprivation nighttime period than on the fourth night (P < 0.05). Pulsatile analysis showed significant reduction of both the 24 h and daytime peak area (P < 0.05) and of the pulse amplitude (P < 0.01), but not of the pulse frequency. Also, the amount of time-integrated GH was significantly higher for the first 4 h of the postdeprivation night compared to the predeprivation night (P < 0.05). Cross-correlation analyses between the absolute values of the time-series of each hormone value and percentage of each sleep stage per half hour revealed that slow wave sleep was negatively correlated with cortisol and positively correlated with GH with slow wave sleep preceding the secretion of these hormones. In contrast, indices of sleep disturbance, i.e. wake and stage 1 sleep, were positively correlated with cortisol and negatively correlated with GH. We conclude that sleep deprivation results in a significant reduction of cortisol secretion the next day and this reduction appears to be, to a large extent, driven by the increase of slow wave sleep during the recovery night. We propose that reduction of CRH and cortisol secretion may be the mechanism through which sleep deprivation relieves depression temporarily. Furthermore, deep sleep has an inhibitory effect on the HPA axis while it enhances the activity of the GH axis. In contrast, sleep disturbance has a stimulatory effect on the HPA axis and a suppressive effect on the GH axis. These results are consistent with the observed hypocortisolism in idiopathic hypersomnia and HPA axis relative activation in chronic insomnia. Finally, our findings support previous hypotheses about the restitution and immunoenhancement role of slow wave (deep) sleep.
    Clinical Endocrinology 08/1999; 51(2):205-15. · 3.40 Impact Factor
  • A N Vgontzas, A Kales
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    ABSTRACT: Sleep disorders are very prevalent in the general population and are associated with significant medical, psychological, and social disturbances. Insomnia is the most common. When chronic, it usually reflects psychological/behavioral disturbances. Most insomniacs can be evaluated in an office setting, and a multidimensional approach is recommended, including sleep hygiene measures, psychotherapy, and medication. The parasomnias, including sleepwalking, night terrors, and nightmares, have benign implications in childhood but often reflect psychopathology or significant stress in adolescents and adults and organicity in the elderly. Excessive daytime sleepiness is typically the most frequent complaint and often reflects organic dysfunction. Narcolepsy and idiopathic hypersomnia are chronic brain disorders with an onset at a young age, whereas sleep apnea is more common in middle age and is associated with obesity and cardiovascular problems. Therapeutic naps, medications, and supportive therapy are recommended for narcolepsy and hypersomnia; continuous positive airway pressure, weight loss, surgery, and oral devices are the common treatments for sleep apnea.
    Annual Review of Medicine 02/1999; 50:387-400. · 14.60 Impact Factor
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    ABSTRACT: Patients with pathologically increased daytime sleepiness and fa- tigue have elevated levels of circulating interleukin-6 (IL-6). The latter is an inflammatory cytokine, which causes sickness manifes- tations, including somnolence and fatigue, and activation of the hy- pothalamic-pituitary-adrenal axis. In this study, we examined: 1) the relation between serial measurements of plasma IL-6 and quantity and depth of sleep, evaluated by polysomnography; and 2) the effects of sleep deprivation on the nyctohemeral pattern of IL-6 secretion. Eight healthy young male volunteers were sampled for 24 h twice, at the baseline state, after a normal night's sleep and after total over- night sleep deprivation. At the baseline state, IL-6 was secreted in a biphasic circadian pattern with two nadirs at 0800 and 2100 and two zeniths at 1900 and 0500 (P , 0.01). The baseline amount of sleep correlated negatively with the overall daytime secretion of the cyto- kine (P , 0.05). Also, depth of sleep at baseline correlated negatively with the postdeprivation increase of daytime secretion of IL-6 (P , 0.05). Sleep deprivation changed the temporal pattern of circadian IL-6 secretion but not the overall amount. Indeed, during the post- deprivation period, the mean daytime (0800 -2200 h) levels of IL-6 were significantly higher (P , 0.05), whereas the nighttime (2200 - 0600 h) levels were lower than the predeprivation values. Thus, sleep- deprived subjects had daytime oversecretion and nighttime under- secretion of IL-6; the former might be responsible for their daylong somnolence and fatigue, the latter for the better quality (depth) of their sleep. These data suggest that a good night's sleep is associated with decreased daytime secretion of IL-6 and a good sense of well- being and that good sleep is associated with decreased exposure of tissues to the proinflammatory and potentially detrimental actions of IL-6. Sleep deprivation increases daytime IL-6 and causes somno- lence and fatigue during the next day, whereas postdeprivation de- creases nighttime IL-6 and is associated with deeper sleep. (J Clin Endocrinol Metab 84: 2603-2607, 1999)
    Journal of Clinical Endocrinology & Metabolism - J CLIN ENDOCRINOL METAB. 01/1999; 84(8).
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    ABSTRACT: The aim of this study was to assess whether there is an association between chronic insomnia and the activity of the stress system. Fifteen young adult insomniacs (<40 years) were studied. After an adaptation night, each subject was recorded in the sleep laboratory for three consecutive nights. During this period, 24-hour urine specimens were collected for measurements of urinary free cortisol (UFC), catecholamines, and growth hormone (GH). The 24-hour UFC levels were positively correlated with total wake time (p=0.05). In addition, 24-hour urinary levels of catecholamine metabolites, DHPG, and DOPAC were positively correlated with percent stage 1 sleep (p<0.05) and wake time after sleep onset (WTASO) (p<0.05). Norepinephrine tended to correlate positively with percent stage 1 sleep (p=0.063) and WTASO (p=0.074), and negatively with percent slow-wave sleep (p=0.059). Twenty-four-hour urinary GH excretion was detectable in only three insomniacs, two of whom had low indices of sleep disturbance. We conclude that, in chronic insomnia, the activity of both limbs of the stress system (i.e., the HPA axis and the sympathetic system) relates positively to the degree of objective sleep disturbance.
    Journal of Psychosomatic Research 08/1998; 45(1):21-31. · 3.27 Impact Factor
  • Journal of Psychosomatic Research 07/1998; 45(1). · 3.27 Impact Factor

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8k Citations
1,748.71 Total Impact Points

Institutions

  • 1975–2005
    • Pennsylvania State University
      • Department of Psychiatry
      University Park, MD, United States
  • 2004
    • Emory University
      • Division of Endocrinology
      Atlanta, GA, United States
  • 1972–2001
    • Penn State Hershey Medical Center and Penn State College of Medicine
      • • Psychiatry
      • • Department of Surgery
      Hershey, PA, United States
  • 1994
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 1964–1965
    • University of California, Los Angeles
      Los Angeles, California, United States