[Sleep and academic performance in university students: a systematic review]. / Sueño y rendimiento académico en estudiantes universitarios: revisión sistemática.

INTRODUCTION: University students tend to suffer from problems of sleep regularity, quantity and quality, which can affect their academic performance. These problems are related to changes typical of the phase of the life cycle in which they find themselves due to maturational, psychosocial development (associated with the processes of individuation and socialisation) and academic factors. The study of the relationship between sleep and academic performance in university students is an area of research of growing interest, which has started to be studied over the last two decades. AIM: To conduct a systematic review of the existing literature on the relationship between sleep and academic performance in university students. SUBJECTS AND METHODS: The articles included in the PubMed database were selected, following the PRISMA guidelines. Studies evaluating samples of subjects with an average age between 18 and 26 years, published in English or Spanish during the period 2000-2019 were included. Subsequently, the quality of the selected articles was evaluated according to the STROBE standard. RESULTS: Thirty studies were identified, which were grouped according to different aspects of sleep: drowsiness, duration, experience of total sleep deprivation, sleep quality, chronotype, regularity and sleep disorders. CONCLUSION: The results of these studies suggest that inadequate sleep has a negative effect on the academic performance of university students.

TITLE: Sueño y rendimiento académico en estudiantes universitarios: revisión sistemática.Introducción. Los estudiantes universitarios tienden a padecer problemas de regularidad, cantidad y calidad de sueño, que pueden afectar a su rendimiento académico. Estos problemas se relacionan con cambios propios de la fase del ciclo vital en la que se encuentran debido a diversos factores: madurativos, del desarrollo psicosocial (asociados con los procesos de individuación y socialización) y académicos. El estudio de la relación entre el sueño y el rendimiento académico en estudiantes universitarios es un área de investigación de interés creciente, que ha empezado a ser objeto de estudio en las últimas dos décadas. Objetivo. Revisión sistemática de la bibliografía existente sobre la relación del sueño y el rendimiento académico en los estudiantes universitarios. Sujetos y métodos. Se seleccionaron los artículos recogidos en la base de datos PubMed, siguiendo las directrices PRISMA. Se incluyeron los estudios que valoraban muestras de sujetos con una edad media entre 18 y 26 años, publicados en inglés o castellano, durante el período 2000-2019. Posteriormente, se evaluó la calidad de los artículos seleccionados siguiendo la normativa STROBE. Resultados. Se identificaron 30 estudios, que fueron agrupados según distintos aspectos del sueño: somnolencia, duración, experiencia de privación total de sueño, calidad de sueño, cronotipo, regularidad y trastornos del sueño. Conclusión. Los resultados de estos estudios sugieren que un sueño inadecuado afecta negativamente al rendimiento académico de los estudiantes universitarios.

Short sleep duration and obesity: the role of emotional stress and sleep disturbances.

OBJECTIVE: Many epidemiologic studies have reported that obesity is associated with short sleep duration. How the degree of obesity or other clinical characteristics of the obese individuals, such as sleep disturbances or emotional stress, define this relation is not known. DESIGN: We studied a random sample of 1300 middle-aged men and women from the Penn State Cohort in the sleep laboratory for one night. Sleep disturbances were recorded as insomnia, excessive daytime sleepiness (EDS) or sleep difficulty. Chronic emotional stress was determined by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: Obese individuals (body mass index, BMI>30) reported shorter duration of sleep, had a higher incidence of subjective sleep disturbances (47.4 vs 25.5%; P<0.01) and scored higher for chronic emotional stress than nonobese subjects. However, there was no difference in self-reported sleep duration between obese and nonobese individuals without subjective sleep disturbances, while both obese men and women with sleep complaints scored higher in the MMPI-2 compared to obese individuals without sleep complaints. The shortest sleep duration was reported by the obese insomniac patients (5.9 h), followed by obese with EDS (6.3 h) or sleep difficulty (6.6 h). The effect of chronic emotional stress was stronger than that of the BMI on the reported sleep duration, with a synergistic joint effect. The presence of a sleep disturbance was associated with a reduction of reported sleep by 18 min for men and 42 min in women, whereas a 10 kg m(-2) increase of BMI was associated with a 16 and 6 min decrease of sleep in men and women, respectively. Interestingly, there was no association between objective sleep duration and BMI. CONCLUSION: Self-reported short sleep duration in obese individuals may be a surrogate marker of emotional stress and subjective sleep disturbances, whose detection and management should be the focus of our preventive and therapeutic strategies for obesity.

Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression.

CONTEXT: Excessive daytime sleepiness (EDS) is commonly considered a cardinal sign of sleep apnea; however, the mechanism underlying the association is unclear. OBJECTIVE: 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. DESIGN AND SETTING: 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. MAIN OUTCOME MEASURE: The main measure was a complaint of EDS. RESULTS: 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. CONCLUSIONS: 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.

Association of hypertension and sleep-disordered breathing.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Environmental factors in the development of narcolepsy with cataplexy. A case-control study.

INTRODUCTION: Epidemiological studies suggest the importance of environmental factors in the etiology of narcolepsy-cataplexy in genetically predisposed subjects. AIM: To assess the role of environmental factors in the development of narcolepsy-cataplexy, using a case-control design with control subjects being matched for ethnicity and age. PATIENTS AND METHODS: All patients were recruited through two outpatient clinics at the community of Madrid, ant the diagnosis of narcolepsy fulfilled the criteria of the International Classification on Sleep Disorders-2005. A questionnaire, including 54 environmental psychological stressor life events and 42 infectious diseases items, was administered to 54 patients. We specifically assessed the stressful factors and infectious diseases that occurred in the year preceding the onset of the first symptom of narcolepsy (excessive daytime sleepiness and/or cataplexy). The same questionnaire was administered to 84 control subjects recruited from non-related family members of the same community. RESULTS: Fifty four patients (55.6% males) answered the questionnaire, The mean age at onset of the first symptom was 21.6 ± 9.3 years, and the mean age at diagnosis was 36.5 ± 12.4 years. The main finding in narcoleptic patients as compared to control subjects was major changes in the 'number of arguments with partner, family, or friends' (odds ratio: 5.2; 95% confidence interval: 1.8-14.5). This can be interpreted as having a protective function and it suggests that psychological mechanisms are present since the beginning of the disease. As for the infectious factors, chickenpox was the most frequently reported. No significant differences were found in terms of total numbers of stress-related and infectious factors between cases and controls. CONCLUSION: Prospective studies regarding the interaction between environmental and genetic factors are warranted.

TITLE: Factores ambientales en la etiologia de la narcolepsia-cataplejia. Estudio de casos y controles de una serie.Introduccion. Los estudios epidemiologicos subrayan la importancia de los factores ambientales en la etiologia de la narcolepsia con cataplejia en pacientes geneticamente predispuestos. Objetivo. Evaluar el papel de los factores ambientales en la etiologia de la narcolepsia-cataplejia utilizando un diseño de casos y controles comparados por edad y etnia. Pacientes y metodos. Todos los pacientes fueron diagnosticados en nuestras unidades de sueño, segun los criterios de la Clasificacion Internacional de los Trastornos del Sueño de 2005. Utilizamos un cuestionario consistente en 54 preguntas relacionadas con acontecimientos psicologicos estresantes y 42 enfermedades infecciosas en 54 pacientes. Evaluamos especificamente la presencia de factores estresantes y/o infecciosos en el año previo al comienzo del primer sintoma de narcolepsia-cataplejia (somnolencia excesiva diurna y/o cataplejia). El mismo cuestionario se administro a 84 controles, miembros de la misma comunidad, sin relacion de parentesco. Resultados. Respondieron el cuestionario 54 pacientes (55,6%, hombres) (edad media del primer sintoma: 21,6 ± 9,3 años; edad media del diagnostico: 36,5 ± 12,4 años) y 84 controles. El principal hallazgo fue un cambio importante en el 'numero de discusiones con la pareja, la familia o los amigos' (odds ratio: 5,2; intervalo de confianza al 95%: 1,8-14,5) en los narcolepticos, lo que sugiere que los mecanismos psicologicos estan presentes desde el comienzo de la enfermedad con una funcion protectora. La varicela fue el factor infeccioso mas frecuente. No se obtuvieron diferencias significativas en el numero de factores psicologicos estresantes e infecciosos entre los pacientes narcolepticos y los controles. Conclusion. Estudios prospectivos epidemiologicos en series de individuos susceptibles geneticamente estan justificados para aclarar la implicacion de los factores ambientales en la etiopatogenia de la narcolepsia-cataplejia.

Rapid eye movement sleep correlates with the overall activities of the hypothalamic-pituitary-adrenal axis and sympathetic system in healthy humans.

To assess the association of the overall amount of rapid eye movement (REM) sleep and the activities of the hypothalamic-pituitary-adrenal axis and sympathetic system, we performed polysomnography and measured 24-h urinary free cortisol and catecholamine excretion in 21 healthy adults. After an adaptation night, each subject was recorded in the sleep laboratory for 3 consecutive nights while 24-h urine specimens were collected. Urinary free cortisol, epinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid levels were significantly and positively correlated with the average values of percent REM sleep (P < 0.05). There were no correlations between hormone values and REM latency, other variables of REM distribution, or REM density, an index of phasic activity during REM sleep. The positive correlations between stress system activity and REM sleep are consistent with hormonal and sleep alterations in melancholic depression, a state characterized by increased cortisol and catecholamine secretion.

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

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.

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

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.

Quazepam and flurazepam: long-term use and extended withdrawal.

Two investigation benzodiazepine hypnotics with long half-lifes, (30 and 15 mg quazepam and 30 mg flurazepam) were evaluated in 47-night sleep laboratory studies. The effectiveness and side effects of these benzodiazepines were assessed during short-, intermediate-, and long-term use. Subjects were also assessed for presence of rebound insomnia during the 15 days following abrupt withdrawal. Quazepam, 15 and 30 mg, and flurazepam, 30 mg, each were effective in sleep induction and maintenance after short- and intermediate-term use. Some loss of effectiveness was noted during long-term use of both doses of quazepam and, to a lesser extent, of flurazepam. Subjective reports of improvement in sleep latency and total sleep time were in general agreement with the objective data. During the 15 nights after abrupt withdrawal of these two long-half-life drugs there was no rebound insomnia, either immediate or delayed. Both drugs exerted carry-over effectiveness on the first 2 to 3 nights after withdrawal; with quazepam this effect persisted throughout the withdrawal period. Quazepam, 30 mg, induced frequent side effects related to sleepiness. Side effects noted with 30 mg flurazepam were less frequent and severe, while the side effects with 15 mg quazepam were minimal. These data suggest that the optimal dose of quazepam is 15 mg.

Effects of nadolol on blood pressure, sleep efficiency, and sleep stages.

The effects of nadolol (20 and 80 mg) on blood pressure and sleep parameters were assessed in six patients with mild hypertension. A 32-night experimental protocol in the sleep laboratory was instituted consisting of four placebo-baseline nights followed by 4 weeks of drug administration. Both doses of nadolol had a clear-cut and consistent lowering effect on blood pressure throughout the night and during the day, with a greater reduction noted with the 80 mg dose. In fact, blood pressure values were reduced to normotensive levels. Neither dose had a disrupting effect on sleep, whereas the 80 mg dose improved sleep efficiency and also had a rapid eye movement-enhancing effect. This absence of sleep-disrupting effects is attributed to nadolol's low level of lipophilicity and lack of intrinsic sympathomimetic activity. The clinical significance of the lack of sleep disruption and possible improvement of sleep with nadolol is discussed in light of the well-recognized sleep disturbances produced by other beta-blockers.

Comparison of short and long half-life benzodiazepine hypnotics: triazolam and quazepam.

Two benzodiazepine hypnotics, triazolam, 0.25 mg, with a short elimination t1/2, and quazepam, 15 mg, with a long t1/2, were evaluated in 22-night sleep laboratory studies. Quazepam improved sleep significantly during both short- and intermediate-term use. Daytime sleepiness, which decreased with continued use, was the side effect most often associated with quazepam dosing. In contrast, triazolam dosing did not significantly improve any of the major sleep efficiency parameters, and there was a rapid development of tolerance for the drug's slight initial effectiveness. In addition, there were a number of behavioral side effects including amnesia, confusion, and disinhibition. Withdrawal of triazolam was associated with sleep and mood disturbances (rebound insomnia and rebound anxiety), whereas quazepam exerted carryover effectiveness. Thus the data in this study show that the 0.25 mg dose of triazolam, which is being prescribed increasingly, has a profile of side effects that is similar to that of the 0.5 mg dose.

Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines.

In three parallel groups, brief and intermittent administration and withdrawal of triazolam, 0.5 mg, temazepam, 30 mg, and placebo were assessed in a 12-night sleep laboratory study of 18 subjects with insomnia. With this intermittent schedule both drugs improved sleep, with about one-third reduction in total wake time; this reduction was significant for temazepam but not for triazolam. Even though the periods of drug administration were quite brief, withdrawal of triazolam consistently produced rebound insomnia, with increases in total wake time above baseline of 61% and 51%, respectively, for the first night of each withdrawal period. With temazepam this effect was more variable, with total wake time increased only with the second withdrawal period (39%). Thus these findings indicate that even under conditions of brief, intermittent use and withdrawal, triazolam and, to a lesser degree, temazepam produce rebound insomnia after abrupt withdrawal, thereby predisposing to drug-taking behavior and increasing the potential for drug dependence.

Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal.

Two benzodiazepine hypnotics, one with an intermediate elimination t1/2 (temazepam, 15 mg) and the other with a long t1/2 (quazepam, 15 mg), were evaluated in 22- night sleep laboratory studies. The effectiveness and side effects of these benzodiazepines were assessed during short- and intermediate term use. Subjects were also assessed for the presence of rebound insomnia after abrupt withdrawal. Quazepam, 15 mg, was significantly effective in improving sleep both with short- and intermediate-term use, but the effectiveness of temazepam was considerably less. Although temazepam was effective for maintaining sleep with short-term use, there was rapid development of tolerance for this effect with intermediate-term use. Temazepam did not produce any behavioral side effects during either drug condition. The only side effect associated with quazepam was a significant degree of daytime sleepiness. After its withdrawal, temazepam was associated with some sleep and mood disturbance on the first withdrawal night, whereas quazepam had carryover effectiveness.

Biopsychobehavioral correlates of insomnia, V: Clinical characteristics and behavioral correlates.

The authors compared two large samples of insomniac patients with a group of control subjects. Sleep difficulty usually began before the age of 40 and generally persisted for many years (average duration, 14 years). Several characteristic behaviors were correlated with the symptom of insomnia. During the day and at bedtime, patients reported difficulty relaxing and frequently described themselves as tense, anxious, overly preoccupied, worried, and depressed. Reports of poor mental and physical health were far more prevalent in the insomniac patients than in control subjects. These results indicate that psychiatric factors need to be a primary focus in the multidimensional treatment of chronic insomnia.

Sleep in the Prader-Willi syndrome. Clinical and polygraphic findings.

Nine patients with the Prader-Willi syndrome, ranging in age from 3 to 21 years, were examined clinically as well as studied in the sleep laboratory. They had striking disturbances of sleep-wakefulness patterns. All patients except one had the symptom of excessive daytime sleepiness. The most striking finding was the presence in five patients of rapid-eye-movement (REM) sleep occurring at sleep onset (SOREM). None of the patients had the condition of sleep apnea. One patient, however, demonstrated severe hypoventilation during REM sleep; the lowest value recorded for O2 saturation was 40%, with a consistent value below 50% for as long as ten to 15 minutes. Previous findings have indicated that the Prader-Willi syndrome is of hypothalamic origin. We hypothesize that both the SOREM and O2 desaturation findings in our patients with the Prader-Willi syndrome are also a result of hypothalamic changes.

Narcolepsy-cataplexy. I. Clinical and electrophysiologic characteristics.

The development, clinical course, and electrophysiologic characteristics of narcolepsy were evaluated in 50 adults who had a current complaint of sleep attacks and cataplexy. In most of the patients, the first symptoms, usually excessive daytime sleepiness and sleep attacks, developed during childhood or adolescence. The condition was invariably chronic. Patients frequently had family histories of some disorder of excessive daytime sleepiness. In nocturnal sleep or daytime nap recordings, all but three of the patients demonstrated a rapid-eye-movement (REM) period at sleep onset. Sleep apnea was found in only one patient. Our findings indicate that sleep laboratory recordings to detect a sleep-on-set REM period are of little diagnostic value when the narcoleptic patient has cataplexy. Furthermore, narcoleptic patients require sleep laboratory evaluation for sleep apnea only when the presence of apnea is suggested by the sleep history.

Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome.

To assess whether sleep abnormalities are related to the genetic abnormalities in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) and determined the chromosome 15 genotypes in eight patients with PWS. Four patients demonstrated sleep onset REM periods (SOREM), and five met the objective polysomnographic criteria for severe or moderate excessive daytime sleepiness (EDS). Three of the four patients with SOREM displayed a paternally derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal uniparental heterodisomy in this chromosomal region (UPD). Two of the four patients that did not display SOREM carried paternally derived deletions; the remaining two demonstrated UPD. Four of the five patients with EDS displayed paternal deletions, and the fifth exhibited UPD. One of three patients without evidence of EDS demonstrated paternal deletion; the remaining two showed UPD. Although neither EDS nor SOREM was not consistently associated with a specific genetic abnormality, these phenotypes may be more common in patients with paternal deletions than in those UPD. Sleep abnormalities in PWS cannot be explained by a single genetic model.

Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime.

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.

Sleep apneic activity in older healthy subjects.

The percentage of subjects with sleep apneic activity was significantly greater in a group of 60 healthy subjects who were 50 yr and older compared with a control group of 69 subjects who were younger than 50 yr. Sixteen of the older subjects (26.7%) and six of the younger subjects (8.7%) met the criteria for sleep apneic activity, i.e., 3-29 episodes per night. However, only one of the older subjects (1.7%) had enough sleep apneic activity (30 or more episodes in a night) to meet the definition of the condition of sleep apnea. In both age groups, sleep apneic activity (SAA) was slightly more prevalent in males than females. Older subjects with SAA were not significantly heavier than those without SAA but were so when compared with the younger subjects with SAA. In the 29 older subjects for whom hemoglobin O2 saturation (Sao2) was recorded, those with SAA had a significantly lower mean minimum Sao2 value (87%) than those without (92%).

Alprazolam: effects on sleep and withdrawal phenomena.

Alprazolam was evaluated in chronic insomniacs in a 1-mg bedtime dose. The 16-night sleep laboratory protocol included four placebo-baseline nights followed by seven nights of drug administration and five placebo-withdrawal nights. On the first three drug nights (nights 5 to 7), the drug was highly effective in inducing and maintaining sleep with this short-term use. By the end of the one week of administration (nights 9 to 11), however, the drug had lost about 40% of its efficacy. During drug use, one subject reported some difficulty in controlling expression of inappropriate emotions when interacting with others, which suggested the presence of disinhibition. On the third night following drug termination, there was a significant increase in sleep difficulty above baseline levels (rebound insomnia). This worsening was of comparable magnitude to the peak improvement of sleep with drug administration. Thus, the clinical utility of alprazolam when administered to insomniac patients appears to be limited because of a relatively rapid development of tolerance and possible disinhibitory reactions during drug use and the occurrence of rebound insomnia following withdrawal.