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[Psychological results of mental performance in sleep deprivation].

To quantify the effects of sleep periods that have different lengths of time during continuous operations (CONOPS) 2 independent groups of subjects performed several cognitive tasks for 3 days. The 72 h trial period contained three 60-min sleep periods for the 10 subjects of the experimental group and three sleep periods of 4 h each for the 14 subjects of the control group. With the exception of only one subtest the statistical analyses of the test results of the 2 groups show no significant differences in cognitive performance. It is suggested that high motivation is responsible for comparable performance of the subjects, which was essentially obtained by a monetary pay system for successful test performance.

Adult↗

Renin-angiotensin-aldosterone system, HPA-axis and sleep-EEG changes in unmedicated patients with depression after total sleep deprivation.

BACKGROUND: Changes in the activity of the renin-angiontensin-aldosterone system (RAAS) in depression have recently been reported. Renin and aldosterone secretion are coupled to sleep in healthy subjects. As total sleep deprivation (TSD) leads to a rapid mood improvement in patients with depression, it is of interest to investigate its effect on the response of the RAAS in the recovery night in this population as a possible probe for the neurobiological effects of TSD and potentially other rapid acting antidepressive interventions. Additionally we explored the HPA-system and the sleep-EEG-changes. METHODS: We compared the sleep related activity of the RAAS before and after TSD in seven depressed patients. After an accommodation night, a polysomnographic examination was performed between 23.00 h and 7.00 h. This was followed by 40 h of TSD and a second polysomnography. During the examination blood samples were taken in the night every 20 min for analysis of renin, aldosterone, ACTH and cortisol. RESULTS: During recovery-sleep renin was significantly increased (p < 0.05). Aldosterone showed no change. ACTH and cortisol were decreased by trend in the first half of the night. REM-density and intermittent wakefulness was significantly decreased (p < 0.05), whereas slow wave sleep increased by trend in the first half of the night. CONCLUSION: TSD in patients with depression leads to an increase in renin secretion and a concomitant trend for a decrease in HPA axis activity in the recovery night. These changes could be a "fingerprint" of a rapidly antidepressive treatment.

Adrenocorticotropic Hormone↗

The effects of total sleep deprivation on cerebral responses to cognitive performance.

We review the findings from a study utilizing functional magnetic resonance imaging (FMRI) to examine the effects of total sleep deprivation (TSD) on verbal learning, arithmetic, and divided attention. For verbal learning and divided attention, TSD was associated with increased activation in the bilateral prefrontal cortex and parietal lobes. Increased sleepiness after TSD and lower levels of memory impairment were correlated with increased activation in specific regions of the prefrontal cortex and parietal lobes, respectively. The arithmetic task led to significantly decreased activation in the bilateral prefrontal cortex and parietal lobes. Based on this and other data, we hypothesize an adaptive cerebral response during cognitive performance following TSD with the specific pattern of adaptation depending on the specific cognitive processes performed. We discuss the need to test the hypothesis in a variety of ways.

Adaptation, Physiological↗

[Effects of modafinil on visual and auditory reaction abilities and subjective fatigue level during 48 h sleep deprivation].

OBJECTIVE: To investigate the effects of modafinil, a new central stimulant, on visual and auditory motion reaction ability and subjective fatigue level during 48 h sleep deprivation (SD). METHOD: Six male healthy young volunteers were exposed to two 48 h periods of continuous wakefulness during the crossover experiment. In one period, three 200 mg doses of modafinil were given and in the other, separated by two weeks, matching placebos were administered. The SD time started from 7:00 of the first day to 7:00 of the third day. Drugs were given at 0:00, 16:00 of the second day and 0:00 of the third day. Variables, including visual and auditory motion reaction time, attention distribution, critical flicker fusion frequency (CFF), Stanford sleepiness scale (SSS) and rating of perceived exertion (RPE), were tested at 21:00 of the first day and 1, 3, 5, 7 h after each drug administration. RESULT: After 2-3 does of modafinil, the CFF level was obviously enhanced while the scores of Stanford sleepiness scale and RPE were markedly reduced. The visual and auditory motion reaction ability, as well as the attention distribution, showed no significant change. CONCLUSION: Modafinil can effectively reduced the subjective fatigue and sleepiness levels during SD.

Adolescent↗

Prediction of the antidepressant response to total sleep deprivation of depressed patients: longitudinal versus single day assessment of diurnal mood variation.

The relationship between diurnal variation of mood and the clinical response to total sleep deprivation (TSD) was investigated in 43 depressed patients. The question asked was whether the propensity to produce diurnal variations of mood or the actual mood course on the day before TSD determines the clinical response to TSD. Patients rated their mood three times daily during an experimental period of 56 days. The frequency as well as the amplitude of daily mood changes were assessed during this period. For each patient six TSDs were scheduled: two after days with a positive mood course, two after a negative mood course, and two after days without a diurnal change of mood. This strategy allowed comparisons of TSD responses within patients. Moreover, longitudinally and retrospectively assessed diurnal variation were compared with each other. It was found that patients vary largely in the occurrence of diurnal variations of mood. The propensity to produce diurnal variations either in terms of frequency or amplitude was positively correlated with the response to TSD. Within patients no differences were found in responses to TSDs applied after days with diurnal variations (positive or negative) or without diurnal variations. A second aim was to get more insight into the mechanism relating diurnal variations of mood and the TSD response. Therefore, the interrelatedness of various measures of diurnal variations, such as amplitudes and frequencies of positive or negative diurnal mood changes, was studied, as well as the relationships of these variables with TSD responses. On the basis of the strong interrelatedness it is suggested that they all reflect the same underlying mechanism, to be symbolized by an oscillator, producing positive daily fluctuations of mood.

Adult↗

The effect of sleep deprivation and exercise load on isokinetic leg strength and endurance.

Isokinetic leg strength and fatigue were measured in 24 male U.S. Marine Corps volunteers in a simulated sleep loss and unusually heavy work scenario. Knee extension and flexion peak torque (PT) were measured at three isokinetic speeds (1.57, 2.62 and 3.66 rad.s-1) followed by 45 consecutive maximal reciprocal contractions at 3.14 rad.s-1 to measure fatigue index (FI). All subjects were retested 2 days later following 30-h sleep deprivation (SD). The exercise group (n = 12) spent 25 1-h sessions performing computer tasks, filling out questionnaires and walked 1.61 km with a 50% gross body mass pack load, during each of the 25 sessions. The control group (n = 12) did likewise but did not exercise. Repeated measures ANOVA indicated that flexion PT at 1.57 rad.s-1 decreases (P < 0.013) after SD. Exercise did not affect FI but did decrease PT. It was concluded that carrying a 50% load produces decrements in PT for both extension and flexion but more so for flexion. SD affected PT but had no effect on FI.

Creatine Kinase↗

Electrodermal activity during total sleep deprivation and its relationship with other activation and performance measures.

The present study analyses the variations of the skin resistance level (SRL) during 48 h of total sleep deprivation (TSD) and its relationship to body temperature, self-informed sleepiness in the Stanford Sleepiness Scale (SSS), and reaction time (RT). All of the variables were evaluated every 2 h except for the SSS, which was evaluated every hour. A total of 30 healthy subjects (15 men and 15 women) from 18 to 24 years old participated in the experiment. Analyses of variance (ANOVAs) with TSD days and time-of-day as factors showed a substantial increase of SRL, SSS, and RT, and a decrease in body temperature marked by strong circadian oscillations. The interaction between day by time-of-day was only significant for RT. Furthermore, Pearson's correlations showed that the increase of SRL is associated to the decrease in temperature (mean r=-0.511), the increase of SSS (mean r=0.509), and the deterioration of RT (mean r=0.425). The results support previous TSD reports and demonstrate the sensitivity of SRL to TSD. The non-invasive character of SRL, its simplicity, and its relationships with other activation parameters, widely validated by previous literature, convert SRL into an interesting and useful measure in this field.

Adolescent↗

Sleep homeostasis in suprachiasmatic nuclei-lesioned rats: effects of sleep deprivation and triazolam administration.

The electroencephalogram (EEG) and electromyogram of rats with lesions in the suprachiasmatic nuclei (SCNx) were recorded during two series of 24-h baseline, 6-h sleep deprivation (SD), and 24-h recovery. At recovery onset, rats were injected i.p. with vehicle (VEH) control solution or 0.4 mg/kg triazolam (TRZ) in a balanced crossover design. Consecutive 10-s epochs were scored for vigilance states and EEG power spectra were computed. Arousal states were uniformly distributed during 24-h baseline (wake 47% of recording time, non-rapid-eye movement sleep (nonREMS) 47%, REMS 7%), and EEG spectra (0-25 Hz) were devoid of significant trends. State-specific EEG power spectra profiles in SCNx rats were similar to those of intact animals reported previously. However, EEG delta power (0.5-3.5 Hz) of nonREMS was markedly lower in SCNx rats. Recovery from 6-h SD was characterised by a short-lasting reduction of REMS, and a long-lasting increase of nonREMS time at the cost of wakefulness. EEG delta power rebounded during the first 8 h in recovery, and fell below baseline level after 12 h in recovery. During 0-2 h TRZ recovery, rats spent more time in nonREMS with higher EEG slow wave activity as compared to the corresponding VEH recovery period. EEG slow wave activity fell below baseline levels 10 h after TRZ injection and termination of SD. We conclude that major features of homeostatic sleep EEG regulation are present in SCNx rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sustaining helicopter pilot performance with Dexedrine during periods of sleep deprivation.

BACKGROUND: Around-the-clock operations often are mandated in combat, but while aircraft can function effectively throughout continuous 24-hour periods, aviators often cannot because of sleep loss. An efficacious countermeasure in sustained operations may be the administration of dextroamphetamine (Dexedrine). HYPOTHESIS: Dexedrine will effectively prevent many of the performance problems associated with sleep deprivation in helicopter pilots. METHODS: A placebo-controlled, double blind study was conducted. Six U.S. Army helicopter pilots completed five flights in a UH-60 simulator while their performance was evaluated. Immediately following each flight, data were collected on electroencephalographic (EEG) activity and subjective mood ratings. Testing sessions occurred at 0100, 0500, 0900, 1300, and 1700. One hour prior to each of the first three flights on drug-administration days, the aviators were given 10 mg of Dexedrine or placebo. RESULTS: Dexedrine, in comparison to placebo, improved aviator simulator control on descents, straight-and-levels, standard-rate turns, and a left-descending turn. Performance was facilitated most noticeably at 0500, 0900, and 1700 (after 22, 26, and 34 hours of continuous wakefulness). EEG and mood data showed that alertness was sustained significantly by Dexedrine--there was reduced slow-wave EEG activity and improved rating of vigor and fatigue. No adverse behavioral or physiological effects were observed. CONCLUSIONS: Dexedrine appears to be effective for sustaining helicopter pilot performance during short periods of sleep loss without producing adverse side effects.

Adult↗

Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans.

BACKGROUND: Chronic mental and physical stress has been suggested to be a trigger for cardiovascular events. In addition, a reduction in levels of intracellular magnesium has been reported to cause vasoconstriction while enhancing platelet-dependent thrombosis. HYPOTHESIS: The purpose of this study was to investigate whether chronic stress affects endothelial function and intracellular magnesium levels in humans. METHODS: Flow-mediated dilation (endothelium-dependent vasodilation) and sublingual nitroglycerin-induced dilation (0.3 mg, endothelium-independent vasodilation) were measured in the brachial artery in 30 healthy male college students, aged 22 +/- 1 years, using high-resolution ultrasound both before and immediately after a 4-week final term examination period. Erythrocyte magnesium concentration was measured simultaneously. All students had chronic sleep deprivation for 4 weeks, during which sleep lasted < 80% of that on ordinary days; in addition, the students were under great stress to pass the examination. This condition was considered to be chronic stress. RESULTS: Chronic stress decreased flow-mediated dilation and erythrocyte magnesium concentration (from 7.4 +/- 3.0 to 3.7 +/- 2.3%, p < 0.05; from 5.7 +/- 0.4 to 5.5 +/- 0.4 mg/ml, p < 0.05, respectively). The change in flow-mediated dilation correlated significantly with that of the erythrocyte magnesium concentration (r = 0.43, p < 0.05), but not with nitroglycerin-induced dilation. CONCLUSIONS: Chronic stress was found to attenuate endothelial function, which may also be associated with a reduction in the intracellular magnesium level in humans.

Adult↗

Sleep deprivation increases brain serotonin turnover in the rat.

IN order to study possible time-dependent changes in serotonin metabolism in rat brain, male Wistar rats were subjected to 3, 6 or 12 h total sleep deprivation (SD) by gentle handling. In addition two groups of rats subjected first to 6 h SD were allowed 2 or 4 h rebound sleep. Tissue concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured from several brain areas using HPLC/ECD. SD significantly increased the 5-HIAA/5-HT ratio in frontal cortex, hippocampus, hypothalamus and brain stem, indicating increased 5-HT turnover in those areas. After 2 and 4 h rebound sleep, the 5-HIAA/5-HT ratio was similar to that in controls. We conclude that a short SD increases 5-HT turnover in the rat brain for the duration of SD only.

Animals↗

Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment--neurobiological and psychometric assessment of course.

The present study was designed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation (SD) or bright light (BL) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response. We used (1) the combined dexamethasone-corticotropin releasing hormone test (DEX-CRH test) to characterize alterations of the hypothalamic-pituitary-adrenal (HPA) system; (2) polysomnography to evaluate sleep disturbances; and (3) a standardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment. The overall response rate (> or = 50% decrease in score on Hamilton Rating Scale for Depression [HRS]) was 55% (N = 42). The response rate in the group with trimipramine monotherapy (N = 14) was 79%, whereas in the groups with adjunct SD (N = 14) and BL (N = 14), respectively, it was only 43%. All three groups showed significant improvement at the end of the third week of treatment. Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS. A significantly higher proportion of nonresponders than responders (p < .05) had HPA dysregulation, disturbed rapid eye movement (REM) sleep (REM latency, REM% first third of night) and decreased non-REM sleep (% stage 2). The non-responders showed significantly more corticotropin (ACTH) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation (cortisol secretion) (p < .01). In addition, REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group. REM latency, percentage of REM sleep during the first third of the total sleep period, percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups. The neurobiological symptoms were unevenly distributed, among the three groups, thus creating heterogeneity in these measures. This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology (HRS). In contrast, the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups: The onset of improvement in simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups. This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome.

Adrenocorticotropic Hormone↗

Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow?

The possible predictive value of regional cerebral perfusion patterns with respect to the response to partial sleep deprivation (PSD) was evaluated in 15 major depressive patients (mean age = 54.9 years, mean Hamilton depression score = 21.6). Patients were studied with single photon emission computed tomography with technetium-99 m-D,L-hexamethyl-propylene amine oxime. Scans were performed on the morning before and after (at 08.00 h) PSD. Responders to PSD had significantly higher perfusion in the right orbitofrontal cortex than did non-responders before PSD. Multiple regression analysis indicated that right orbitofrontal/basal cingulate perfusion (r = -0.77, P < 0.001) before PSD, and left inferior temporal perfusion (r = 0.59, P = 0.01) after PSD, were fairly accurate predictors of change in Hamilton depression scores. Thus, it appears that the orbitofrontal cortex and the cingulate are involved in PSD and may serve as predictors of therapeutic response.

Adult↗

Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in intact and ovariectomized rats compared with male rats.

The purpose of this study was to investigate the effects of paradoxical sleep deprivation (PSD) on circulating lipoproteins (total cholesterol, HDL, LDL and triglycerides) in males as well as in intact and ovariectomized (OVX) female rats. The intact female rat group was sub-distributed according to the phase of the estrous cycle (proestrus, estrus and diestrus) allowing for comparison of the lipid profile with males and OVX rats. The results indicate that PSD significantly reduced cholesterol in intact females compared to OVX and male rats; it reduced triglycerides in all groups except in diestrus rats and increased HDL levels in male rats compared with the respective controls. PSD also increased LDL levels in male and OVX rats when compared to intact females. Examinations of cholesterol fractions revealed significant increases in HDL in control-OVX animals when compared to the other groups, whereas HDL was significantly increased after PSD in male rats. Such results suggest that the cardiovascular response in intact, OVX females and male rats is differentially regulated especially when such are submitted to PSD. Similarities in blood parameters observed between OVX and male rats are likely due to the suppression of ovarian hormone release after ovariectomy.

Animals↗

Dexamethasone suppression test and sleep deprivation in endogenous depression.

The dexamethasone suppression test (DST) was carried out in 24 endogenously depressed and 15 non-endogenously depressed patients before and on the day after therapeutic sleep deprivation (SD) for one night. The diagnostic selectivity of DST results was not improved by combination with SD. The alteration of DST cortisol levels after SD, irrespective of the direction of change (so-called cortisol response) was significantly higher in endogenous depressives than in neurotic depressives. No unequivocal statement was possible on (a) the predictive value of DST data for the SD effect and (b) the relationship between neuroendocrine changes and the antidepressive effect of SD.

Bipolar Disorder↗

Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue.

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.

Adipose Tissue, Brown↗

Effects of long-term food restriction on genital reflexes in paradoxically sleep-deprived male rats.

The purpose was to ascertain whether the different schedules of long-term food restriction (FR) exert influence on genital reflexes (penile erection-PE and ejaculation-EJ) induced by paradoxical sleep deprivation (PSD) in male rats. Diet restriction began at weaning with 6 g/day and food was increased by 1 g per week until reaching 15 g/day by adulthood. Rats submitted to FR and those fed ad libitum were distributed into PSD or maintained as control groups and challenged with saline or cocaine. The results indicated that PSD+saline induced PE and EJ in both ad libitum and FR groups, but cocaine only potentiated reflexes in ad libitum group. In an attempt to revert the effects of FR on genital reflexes, we provided food ad libitum to the restricted group during the PSD period (4 days). When compared to FR rats, an increase in the frequency of PE was observed in the FR group fed ad libitum during PSD (both groups were challenged with cocaine). Further, we sought to investigate motivational behavior by placing food within the behavioral cage during the evaluation of genital reflexes. The FR PSD+saline group challenged with food did not display genital reflexes but when injected with cocaine the responses were similar to those observed in FR PSD+cocaine rats not challenged with food. Our data suggest that the facilitatory effect of PSD on genital reflexes did not override the inhibitory effect of FR on erectile function, but different schedules of FR produce distinct effects on genital reflexes. Further studies are warranted to dissect the effect of food restriction on sexual behavior.

Animals↗