Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The circadian rhythms of plasma cortisol was examined in 25 persons aged between 70 and 100 years by comparison with 5 adults aged between 17 and 38 years. The blood samples were drawn at 16 hundred, 20 hundred, 00 hundred, 04 hundred and 08 hundred hrs. Cortisol was assayed by the fluorimetric method. The experimental data were analyzed by Halberg's mean-cosinor method. The results showed that the circadian rhythm in plasma cortisol changes with age. The characteristic phenomena found were the following: a tendency towards reducing the hourly quantitative differences, comparatively more marked between 90 and 100 years; anticipation of the cortisol maximum level of 08 hundred at 04 hundred hrs in the group of 71 to 80 years, and at 00 hundred hrs in some of the subjects older than 80. A normal circadian rhythm was found in 2 of the 25 cases examined. These changes imply variations of the same kind in the CRF and ACTH levels. The changes in the circadian rhythms of cortisol show that the regulation systems are also implied in the aging process. It is possible that early-morning insomnia of the aged be due to this anticipation in cortisol secretion.
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PMID:Cortisol circadian rhythm in 70--100-year-old subjects. 63 32

To explore whether possible differences in central nervous system neuromodulators contribute to the differential presentation of affective symptomatology in Cushing's disease and major depression, we examined the levels of immunoreactive CRH and ACTH in the cerebrospinal fluid (CSF) of 11 patients with Cushing's disease, a patient with ectopic ACTH secretion, 34 patients with major depression, and 60 healthy subjects. We elected to measure these peptides not only because both are classically involved in pituitary-adrenal regulation, but also because their primarily arousal-producing and anorexigenic behavioral effects in experimental animals suggest that they may play a role in the symptom complex of depressive syndromes. We also explored whether the CSF levels of these peptides were more helpful in determining the often difficult differential diagnosis between major depression and Cushing's disease than the plasma ACTH response to ovine CRH, a currently used but somewhat insensitive laboratory means of distinguishing these disorders. CSF levels of immunoreactive CRH and ACTH were significantly lower in Cushing's disease patients [21.9 +/- 2.7 and 15.4 +/- 1.8 pg/mL, (mean +/- SEM), respectively] compared to patients with major depression [38.4 +/- 2.3 pg/mL (P less than 0.01) and 24.5 +/- 1.6 pg/mL (P less than 0.01), respectively] and controls [38.4 +/- 1.6 pg/mL (P less than 0.001) and 26.3 +/- 1.1 pg/mL (P less than 0.001), respectively]. The coexistence of high plasma ACTH and low CSF ACTH in Cushing's disease yielded a CSF/plasma ACTH ratio consistently less than that in depressed patients, with only 2 of 31 subjects comprising both groups showing values that overlapped. In contrast, 9 of the combined patients showed ACTH responses to ovine CRH that overlapped. These data suggest that differences in centrally directed CRH secretion may account for the differential presentation of the dysphoric syndromes seen in major depression and Cushing's disease. Hence, the classic form of major depression (melancholia), is often associated with evidence of pathological hyperarousal, such as intense anxiety, sleeplessness, and anorexia, while that of Cushing's disease is associated with evidence of pathological hyperarousal, including hyperphagia, fatigue, and inertia. Moreover, measurement of the CSF/plasma ACTH ratio may serve as a clinically useful adjunct to the ovine CRH stimulation test and other laboratory measures in determining the differential diagnosis between major depression and Cushing's disease.
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PMID:Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications. 199 96

Thirty-five consecutive patients with Cushing's syndrome were studied prospectively prior to treatment. A consistent constellation of psychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased concentration and memory), and vegetative functions (decreased libido and insomnia). A statistically significant relationship was found between the overall psychiatric disability rating and cortisol and ACTH level. The relationship of depressed mood and hormone levels was examined. Low ACTH levels were significantly associated with milder rather than pronounced depressed mood. The implications of the similarities in psychiatric manifestations between Cushing's syndrome and the primary affective disorders are discussed.
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PMID:Depressed mood and other psychiatric manifestations of Cushing's syndrome: relationship to hormone levels. 625 80

Thirty-two patients with various severe or selected dermatoses were chosen for treatment with cortisone acetate by mouth. The criteria for selection included refractoriness to previous therapy and absence of ascertainable contraindications. The initial dose of cortisone acetate varied between 100 and 200 mg. per day. The dose was reduced as quickly as each patient's response permitted, with the object of reaching the lowest effective dose as quickly as possible. Response of most patients to the hormone was dramatic, with abatement of symptoms within 24 hours and substantial improvement of clinical signs within 24 to 48 hours. Details of the results are tabulated. Adverse effects, possibly attributable to the hormone, were noted in five patients. In two instances, moon facies developed, one with hypertrichosis and a 20-lb. (9.1-kg.) gain in weight. However, both of these patients had received corticotropin (ACTH) prior to the cortisone. A third patient showed hyperpigmentation of the areas of skin usually exposed and not covered by clothing. Two additional patients each complained of hyperexcitability and insomnia. All these undesirable effects diminished or disappeared after the dose was reduced or administration of cortisone was discontinued. The effectiveness of this new therapeutic approach in a wide variety of skin diseases is clearly demonstrated by the excellent response noted in this series of selected cases. No other modality known to us has comparable beneficial effects. It is to be stressed, however, that the benefits generally stop soon after cortisone therapy is discontinued, unless the disease or the attack is one with spontaneous remissions. Disagreeable and sometimes dangerous effects still preclude the use of this treatment except in serious diseases and situations, and unless the patient can be kept under sufficiently close and expert surveillance.
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PMID:Centennial Paper. November 1951 (Arch Dermatol Syphilol: Cortisone acetate administered orally in dermatologic therapy by Marion B. Sulzberger, Victor H. Witten and Stanley N. Yaffe. 635 55

Two peptides known for their hypnogenic properties, CLIP (corticotropin-like intermediate lobe peptide or ACTH 18-39) or VIP (vasoactive intestinal polypeptide), were injected locally into the nucleus raphe dorsalis (nRD) of rats pretreated with p-chlorophenylalanine (PCPA). During the dark period, the PCPA insomnia was primarily associated with a reduction in paradoxical sleep (PS), whereas both slow wave sleep (SWS) and PS were decreased during the light period. Immunohistochemistry of serotonin in PCPA-pretreated animals indicated a clear disappearance of 5-HT fibers in the basal hypothalamus and the nRD as compared to control animals. Local injections of CLIP or VIP in the nRD restored PS and SWS. The positive injection sites corresponded to the anatomical distribution of either CLIP or VIP fibers, i.e., the entire nRD for VIP and the antero-dorsal part of this nucleus for CLIP. The sleep effects obtained in PCPA-pretreated rats involve a non-5-HT sleep permissive component within the nRD upon which these injected peptides act.
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PMID:Sleep permissive components within the dorsal raphe nucleus in the rat. 758 81

According to the hypothesis implying that the main mechanism underlying opiate addiction is the blockade by opiates of NMDA receptor functions and subsequent upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor blocker dextromethorphan (DM) has been successfully used in the heroin addict treatment. As the stimulation of NMDA receptors modulates the release of neurotransmitters and hormones such as NE, D, ACh, GH, LH, LSH, ACTH etc., all of which have been found responsible for the manifestation of abstinence syndrome signs including craving and neuronal death by excessive stimulation of NMDA receptors, the incomplete blockade of the NMDA receptors minimizes the intensity of the abstinence syndrome and provides the downregulation of the receptors. In the present study, tizanidine (TIZ), which inhibits the release of endogenous excitatory aminoacids by the agonistic activity on alpha 2-adrenoreceptors, was combined with DM to obtain further benefits. Forty-four male and three female heroin addicts were the subjects of the study. Their daily mean heroin intake was about 2.28 g street heroin. The main duration of heroin use was approximately 3.4 years. Two to three hours after abrupt withdrawal, the outpatients were given 15 mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TIZ every six hours and 10 mg diazepam + 10 mg hyoscine N-butyl Br + 250 mg dipyrone every six hours three hours following CPZ. The addicts were controlled twice a day. Yawning, rhinorrhea, perspiration, piloerection, restlessness, insomnia, emesis, diarrhea, craving, rejection of smoking and pupils were observed and/or questioned. Two of the 47 outpatients took heroin on the first days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The combination of tizanidine markedly improves the treatment with dextromethorphan of heroin addicted outpatients. 771 85

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.
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PMID:Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: clinical implications. 1129 73

Utilization of the daily rhythm of ACTH secretion was assessed as a measure of the adequacy of replacement therapy in primary chronic adrenal failure (PCAF: Addison's disease) with glucocorticoids (GC) by assaying plasma ACTH by radioimmunoassay every 4 h for one day in three groups of patients. Patients of group 1 had PCAF (n = 14) and received replacement therapy consisting of prednisolone (5 mg at 09:00 and 2.5 mg at 14:00) and group 2 patients received dexamethasone (0.5 mg at 23:00) in combination with prednisolone (2.5 mg at 14:00). All patients with PCAF also received 0.005-0.01 mg/day of 9alpha-fluorocortisol. The control group consisted of 14 healthy volunteers. Both types of replacement therapy resulted in high levels of variability in ACTH levels as compared with that in normal subjects. The areas under the curve (AUC) of the ACTH concentration over one day were not significantly different between groups 1 and 2 or between group 2 and controls. The AUC of ACTH in group 1 was significantly larger than that in controls. The mean ACTH concentration in group 1 at 07:00 and 11:00 was significantly greater than those in the other two groups. The daily rhythm of ACTH was generally closer to normal in patients given dexamethasone. Since our own clinical experience shows that at least two thirds of patients are initially given dexamethasone and that this had to be withdrawn because of the development of overdosage syndrome (weight gain, increased appetite, insomnia), it appears that there is a lack of concordance between the clinical data and the daily rhythm of ACTH secretion. When assessing the adequacy of replacement therapy in PCAF, it is important to note that the appearance of a normal rhythm of ACTH secretion over one day does not exclude the possibility of GC overdosage, with the effect that interpretation of the results of this type of measurement must take the clinical picture into account.
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PMID:The diurnal rhythm of adrenocorticotropic hormone secretion in the assessment of the adequacy of replacement therapy in primary chronic adrenal failure. 1143 May 65

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.
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PMID:Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. 1150 12

Sleep is an important component of mammalian homeostasis, vital for survival. Sleep disorders are common in the general population and are associated with significant medical, psychologic, and social disturbances. Sleep, in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24-hour increase of ACTH and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in the general population, and recent studies have demonstrated that the proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime hypersecretion of IL-6. Combined, these findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
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PMID:Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. 1205 86


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