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PubMed1996

The effect of strenuous exercise, calorie deficiency and sleep deprivation on white blood cells, plasma immunoglobulins and cytokines.

Moderate exercise appears to stimulate the immune system, but there is good evidence that intense exercise can cause immune deficiency. In the present study the authors examined the effect of continuous physical exercise (35% of VO2 max), calorie deficiency and sleep deprivation on the immune system of young men participating in a 5-7 days military training course. There was a two-three fold increase of neutrophils from day 1, the values remained high and decreased slightly at the end of the course. Monocyte counts also increased with a pattern similar to that of neutrophils. Eosinophils decreased to 30% of control and lymphocyte numbers decreased by 30-40%. All the major subgroups (CD4 T cells, CD8 T cells, B cells, NK cells) were reduced. Neutrophil function, as tested by measuring chemotaxis, was significantly stimulated during the first days of the course, in particular in the group with the lowest calorie intake. The mitogenic response of lymphocytes to PHA and Con A was variable, ranging from stimulation during one course to no effect in another course. Serum levels of immunoglobulins decreased significantly during the course. IgG was reduced by 6-7%, IgA by 10-20% and IgM by 20-35%. The authors found no changes of interleukin 1, 2 and 4 during the course, but a (12-20%) reduction (P less than 0.01) of interleukin 6, and an increase (P less than 0.01) of granulocyte-macrophage colony stimulating factor. Altogether the results from the ranger course present a mixed-up picture. The non-specific phagocyte-related immunity was enhanced. On the other hand, the data indicate that even a moderate physical activity, around the clock, caused significant suppression of a number of parameters reflecting the status of the specific, lymphocyte-related immunity. It is noteworthy, however, that there was no significantly increased infection rate during the course or in the first 4-5 weeks thereafter.

Acute-Phase Proteins↗
PubMed1997

Alertness and memory after sleep deprivation and diazepam intake.

Benzodiazepines (BZDs) give rise to memory impairments. It has been questioned whether or not these impairments are related to the drug's sedative, alertness-reducing effects. Therefore, in this study, alertness was reduced in healthy subjects both pharmacologically (15 mg diazepam) and non-pharmacologically (24-h sleep deprivation, SD) in order to assess whether these manipulations both gave rise to memory impairments. Twelve subjects were tested using a repeated measures cross-over design. Drug administration was placebo-controlled and double-blind. A subjective alertness reduction was established after diazepam intake and even more after SD. Additionally, performance-disruptive effects were found on psychomotor tasks after both SD and liazepam intake. However, only diazepam, and not SD, impaired delayed recall of a word list and recall of paired associates. Thus a reduction in alertness, i.e. sedation, cannot fully account for BZD-induced memory impairments.

Adolescent↗
PubMedDate not supplied

Neutral buoyancy and sleep-deprived serum factors alter expression of cytokines regulating osteogenesis.

We examined expression of genes associated with cytokine production, and genes implicated in regulating bone metabolism, in bone stromal and osteoblast cells incubated under standard ground conditions and under conditions of neutral buoyancy, and in the presence/absence of serum from normal or sleep-deprived mice. We observed a clear interaction between these two conditions (exposure to neutral buoyancy and serum stimulation) in promoting enhanced osteoclastogenesis. Both conditions independently altered expression of a number of cytokines implicated in the regulation of bone metabolism. However, using stromal cells from IL-1 and TNFx cytokine(r) KO mice, we concluded that the increased bone loss under microgravity conditions was not primarily cytokine mediated.

3T3 Cells↗
PubMed2000

Sleep in depression and sleep deprivation: a brief conceptual review.

Risk factors for somnipathies are psychological stress or psychiatric illness. More severe sleep difficulties have been found to be clearly related to psychiatric illness such as depression and phobias, as well as to addiction. Somnipathies can objectively be identified by means of polygraphy. Overall, polysomnographic measures in patients with affective disorders differ most frequently and significantly from those in normal control subjects. Persistent sleep disturbances are associated with significant risk of both relapse and recurrence in mood disorders and an increased risk of suicide. In addition to changes in sleep architecture, patients with major depression show profoundly altered patterns of nocturnal hormone secretion, possibly through mechanisms that link regulation of sleep with neuroendocrine activity. Basic and clinical approaches of sleep research established neurobiological models into the underlying pathophysiology associated with psychiatric disorders.

Major Depressive Disorder↗
PubMed1998

The unipolar-bipolar dichotomy and the response to sleep deprivation.

Fifty-one inpatients affected by a major depressive episode were divided into four groups according to mood disorder diagnosis and previous clinical history (bipolar disorder type I; bipolar disorder type II; major depressive disorder with at least three previous depressive episodes; and single depressive episode patients) and administered three consecutive total sleep deprivation (TSD) cycles. Mood changes were rated with a reduced version of the Hamilton Depression Rating Scale and with self-administered visual analogue scales. TSD caused better clinical effects in bipolar and single-episode patients; in particular, unipolar patients lacked effects in perceived mood after the first TSD and showed worse Hamilton ratings in respect to the other groups after the three TSD treatments. Discriminant function analysis could correctly classify 80% of bipolar patients, post hoc, based on TSD response. Further researches on the clinical efficacy of TSD must take into account the heterogeneity of depression and of its biological substrate.

Adult↗
PubMed2005

Combined total sleep deprivation and light therapy in the treatment of drug-resistant bipolar depression: acute response and long-term remission rates.

BACKGROUND: Drug resistance remains a persistent source of morbidity and mortality for patients with bipolar depression. A growing number of clinical studies support the usefulness of chronotherapeutic interventions, such as total sleep deprivation (TSD) and light therapy (LT), in the treatment of nonresistant bipolar depression. METHOD: To investigate the clinical usefulness of TSD plus LT in the treatment of drug-resistant bipolar depression, we treated 60 inpatients for 1 week with repeated TSD and LT combined with ongoing antidepressants and lithium salts. All patients had a DSM-IV diagnosis of bipolar I disorder. Drug resistance was rated according to Thase and Rush criteria. The pattern of relapses and recurrences was assessed during a prospective 9-month follow-up. Data were gathered from September 2002 to July 2004. RESULTS: A 2-way repeated-measures analysis of variance with changes in self-rated perceived mood scores as dependent variable and with time and group (history of drug resistance) as independent factors confirmed significant time-by-group interaction (p = .0339). A logistic regression on rates of achievement of response (50% reduction in Hamilton Rating Scale for Depression ratings) confirmed the significance of observed differences: overall, 70% (23/33) of nonresistant versus 44% (12/27) of drug-resistant patients achieved response (p = .045). A survival time analysis (Cox proportional hazards model) showed that history of drug resistance significantly influenced the pattern of relapses and recurrences, with 57% (13/23) of nonresistant responders and 17% (2/12) of drug-resistant responders being euthymic after 9 months (p = .0212). DISCUSSION: The combination of repeated TSD and LT in drug-resistant patients was useful in triggering an acute response. Further clinical research is needed to optimize this treatment option for drug-resistant patients in the long term.

Adult↗
PubMed1991

Towards a model of mood responses to sleep deprivation in depressed patients.

It is hypothesized that in depressed patients diurnal variation in mood (DV) is a daily recurring phenomenon, which fails to achieve expression on all days (showing a random distribution of DVs). From this perspective a meta-analysis was performed on the raw data of earlier presented studies. The effect of total sleep deprivation (TSD) on mood was examined in 14 so-called prototypical patients, showing on three successive days either positive DVs (feeling better in the evening) or inverse DVs. It was hypothesized that under baseline conditions mood follows a monotonous course with switching points at 7 AM and 11 PM and that during the TSD night the 7-AM switch took place earlier. The position of this switch was calculated, assuming that (1) before the switch the curve ran parallel to the nightly baseline curves, and (2) after the switch the curve showed a monotonous change parallel to the daily baseline curves. The best fit between predicted and measured depression after TSD was found for a switch at 3 AM, varying the switching point during the TSD night with hourly intervals. The characteristics based on prototypical patients contributed significantly to the prediction of the morning and the afternoon depression levels after TSD in a group of 53 patients (prototypical and nonprototypical).

Adult↗
PubMed1997

Self-monitoring cognitive performance during sleep deprivation: effects of modafinil, d-amphetamine and placebo.

Self-monitoring refers to the ability to assess accurately one's own performance in a specific environment. The present study investigated the effects of the stimulating drugs modafinil (300 mg) and d-amphetamine (20 mg) on the ability to self-monitor cognitive performance during 64 h of sleep deprivation (SD) and sustained mental work. Two cognitive tasks were investigated: a visual (perceptual) judgement task and a complex mental addition task. Subjects in the placebo condition displayed marked circadian and SD effects on cognitive task performance but their self-monitoring was substantively undisturbed by SD. Subjects performing under the influence of d-amphetamine likewise displayed highly proficient self-monitoring throughout the SD period. In contrast, modafinil had a disruptive effect on self-monitoring, inducing a reliable 'overconfidence' effect (i.e. an overestimation of actual cognitive performance), which was particularly marked 2-4 h post-dose. Although modafinil has proven to be a safe and effective countermeasure to the effects of extensive SD on cognitive task performance, we encourage a more comprehensive understanding of the relation between its subjective and performance enhancing effects before the drug is recommended as a viable fatigue countermeasure.

Adult↗
PubMed2002

Assessment and cost comparison of sleep-deprived EEG, MRI and PET in the prediction of surgical treatment for epilepsy.

Our aim was to determine if less expensive interictal indices can predict which epilepsy patients may benefit from the more expensive comprehensive pre-surgical evaluation. Surgical treatment was determined based on the results of a comprehensive inpatient continuous video-EEG monitoring. This evaluation included three interictal tests, which were reviewed retrospectively-2 hour-sleep-deprived electroencephalogram (SDEEG), magnetic resonance imaging (MRI), and positron emission tomography (PET). Sixty-nine patients were evaluated with 35 patients having focal resection (33 temporal, two frontal). When two or more interictal tests were positive, 77% (27 /35) went to surgery, but when one test was positive 23% (8 /34) had surgery. When all tests were negative, only a single patient (1 /13 or 7.7%) had surgery, a frontal resection. The positive predictive value for any single interictal test was 68%, while it was higher for any combination of two positive tests (77-83%). PET was the most sensitive (0.86) single interictal test, compared to SDEEG (0.66) and MRI (0.66). The odds ratio for predicting surgical treatment for a positive PET, SDEEG, or MRI was 8.57, 4.01, and 4.01, respectively. MRI was three and PET was six times the cost of a SDEEG. The combination of SDEEG and MRI had the best cost/PPV ratio. Seventy-nine percent (11 /14) of the patients with three positive tests were seizure free following focal resection compared to 43% (9 /21) when less than three tests were positive ( P<or= 0.05). Interictal tests may predict which patients are most likely to benefit from comprehensive pre-surgical evaluation. Two or more positive tests are the most predictive. If all tests are negative, it is unlikely that the patient would qualify for surgical treatment. The combination of SDEEG and MRI may be more cost-effective as outpatient screening tools.

Adolescent↗
PubMed2006

Seven days' around the clock exhaustive physical exertion combined with energy depletion and sleep deprivation primes circulating leukocytes.

Both exhaustive physical exertion and starvation have been reported to induce depression of immune function. The aim of the present study was to investigate the inflammatory environment and state of activation and mediator-producing potential of circulating leukocytes during prolonged physical activity with concomitant energy and sleep deprivation. Eight well-trained males were studied during 7 days of semi-continuous physical activity. Sleep was restricted to about 1 h/24 h, energy intake to 1.5- 3.0 MJ/24 h. Blood was drawn at 07.00 A.M.: on days 0, 2, 4, and 7. Plasma levels of inflammation markers were measured. The response of circulating leukocytes to lipopolysaccharide (LPS; 1 microg mL(-1)), and the effect of added hydrocortisone (10 and 100 nmol L(-1)), were measured in the supernatant after 3 h of incubation in an ex vivo whole blood model. Activation of leukocytes steadily increased as measured by plasma matrix metalloproteinase-9, tumour necrosis factor-alpha, interleukin-1beta, and interleukin-6. Inhibitors of systemic inflammation were either unaltered (tissue inhibitor of matrix metalloproteinase-1) or elevated (plasma interleukin-1 receptor antagonist). Cortisol levels increased on days 2 and 4, but thereafter reverted to baseline values. The leukocytes responded to LPS activation with increasing release of inflammatory cytokines throughout the study period. The anti-inflammatory potency of hydrocortisone decreased. Prolonged multifactorial stress thus activated circulating immune cells and primed them for an increased response to a subsequent microbial challenge.

Adult↗
PubMedDate not supplied

The effect of fatigue, sleep deprivation and onerous working hours on the physical and mental wellbeing of pre-registration house officers.

The potential deleterious effects of doctors' long and arduous shifts have received relatively scant attention. This study addressed the effect of a 32 h on-call shift on 16 pre-registration medical house officers in St. James's Hospital, Dublin. We assessed 5 psychological parameters (Tension-Anxiety, Depression-Dejection, Vigour-Activity, Fatigue-Inertia and Confusion-Bewilderment) as well as 5 simple tests of alertness and concentration both pre- and post-call. The doctors were randomly assigned to be tested either pre- or post-call. On average the doctors got 4.5 hours sleep during a 32 h shift. This long shift had an adverse effect on all the psychological parameters (p < 0.05) except Depression-Dejection. The total mood disturbance score, which has been shown to correlate well with general psychological well-being, deteriorated significantly after the 32 h shift, p < 0.005. Two of the simple tests of alertness and concentration (Trail-making test and Stroop Color-Word test) also showed a significant fall-off in performance with sleep deprivation, p < 0.05, although the remaining tests (Delayed Story Recall, Critical Flicker Fusion and Three Minute Grammatical Reasoning Test) were not significantly impaired by the 32 h shift. This study shows that prolonged periods of duty without sleep adversely affect junior doctors, both in their psychological well-being and in their ability to carry out simple tasks.

Adult↗
PubMed2000

Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat.

The instrumental methods to induce paradoxical sleep (PS) deprivation are stressful. The modified multiple platform method (MMPM), in which animals are placed with new cohorts inside the water tanks, results in augmented ACTH and corticosterone (CORT) responses. We hypothesised that this increased response could be attributed to social instability. In addition, we tested a new environmental control, a grid (GR) placed on the tank floor. Animals were submitted to the MMPM for 4 days as socially unstable (UG--coming from several cages) or stable groups (SG--coming from one cage), placed either on narrow platforms or on the grid. All UG animals presented higher ACTH levels than their SG counterparts, including home-cage controls. CORT levels of manipulated animals were higher than controls only in the stable group. UG animals presented heavier adrenals than their SG counterparts. Only adrenals from SG animals placed on the grid were similar to cage controls. SG rats lost less weight than UG animals. While UG animals ate the same amount of chow as home-cage controls, SG animals ate more than control and UG animals. These results suggest that the stress of the MMPM can be attenuated in stable groups. The introduction of a grid on the tank floor may serve an adequate environmental control as far as stress-related variables are considered.

Adrenocorticotropic Hormone↗
PubMed1993

5-Methoxypsoralen: effect on the noradrenaline circadian rhythm of sleep-deprived subjects.

5-methoxypsoralen (5-MOP), a serotonin analogue, stimulates the secretion of melatonin, which plays an important role in circadian rhythm regulation. Melatonin production is essentially controlled by noradrenaline (NA). To investigate the effect of 5-MOP on the 24 hr NA rhythm, hourly plasma NA concentrations measured over 24 hr in 7 healthy young subjects who took 40 mg 5-MOP orally at 21:00 hr the evening before were compared with values obtained in drug-free subjects. All subjects were sleep-deprived and under conditions in which sympathetic nervous system activation was repeated every hour over 24 hr. In both series of patients, a significant difference was observed between mean morning values and mean night values, reflecting persistence of a circadian rhythm. In subjects given 5-MOP, a significant difference was also observed between mean afternoon values and mean night values. However, MANOVA analysis failed to find any difference between the two series of subjects. Acute administration of 5-MOP thus had no significant effect on the NA circadian rhythm under our study conditions.

5-Methoxypsoralen↗
PubMed2003

Dietary fish oil does not protect rats exposed to restraint or sleep deprivation stress.

It has been suggested that fish oil (FO) prevents weight loss caused by physiological stress such as cancer, injury, or cardiovascular disorders. Previously, we observed that a high-fat diet containing corn and coconut oil exaggerated weight loss caused by the mixed physiological and psychological stress of repeated restraint (RR). This experiment tested the effects of a high-fat diet containing FO as the predominant lipid source in rats exposed to the mixed physiological and psychological stress of either RR or sleep deprivation (SD). FO did not prevent stress-induced hypophagia or weight loss in RR or SD rats but exaggerated the negative effects of stress on body weight in SD rats by promoting loss of lean body mass. RR caused a reduction in body fat content irrespective of dietary treatment. In SD rats, both stress and FO independently reduced body fat mass. FO did not have any effect on adrenal and thymus weights during RR or SD and did not influence corticosterone levels after 1 h of RR or after 48 or 96 h of SD. In conclusion, our results suggest that high levels of dietary FO do not improve the response to stress in rats exposed to mixed stressors.

Adipose Tissue↗