Delayed sleep phase syndrome. A chronobiological disorder with sleep-onset insomnia.

We describe a new syndrome called "delayed sleep phase insomnia." Thirty of 450 patients seen for a primary insomniac complaint had the following characteristics: (1) chronic inability to fall asleep at a desired clock time; (2) when not on a strict schedule, the patients have a normal sleep pattern and after a sleep of normal length awaken spontaneously and feel refreshed; and (3) a long history of unsuccessful attempts to treat the problem. These patients were younger than the general insomniac population and as a group did not have a specific psychiatric disorder. Six patients' histories are described in detail, including the successful nonpharmacological chronotherapy regimen (resetting the patients' biological clock by progressive phase delay). Delayed sleep phase insomnia is proposed to be a disorder of the circadian sleep-wake rhythm in which the "advance" portion of the phase response curve is small.

Daily sleep reports and circadian rest-activity cycles of elderly community residents with insomnia.

Sleep patterns were investigated in 29 insomniacs and 22 controls selected from a large sample of elderly residents of an urban community. According to sleep logs kept for a mean of 14.7 days, insomniacs took longer to fall asleep and stayed awake longer when they woke at night. In 14 insomniacs and 8 controls, wrist movements were monitored with a portable instrument. A circadian rhythm of motor activity was found in both groups, with some notable differences. Insomniacs were more active during periods of bedrest, and their mean daily rest-activity pattern--representing mean activity at equivalent times of day--was flatter. The mean level of activity over the entire experiment was similar in both groups. Insomnia in many elderly persons is thus associated with diffusion of activity over the 24-hr day, leaving bedrest periods only partially filled by rest or sleep.

Cardiac and respiratory activity in panic disorder: effects of sleep and sleep lactate infusions.

OBJECTIVE: This study examined cardiac and respiratory activity in panic disorder patients and healthy comparison subjects during sleep, when the effects of anxious cognition and expectancy set are minimized. METHOD: Heart rate, respiratory rate, end-tidal PCO2, and oxygen saturation were recorded for 11 panic disorder patients and 12 comparison subjects before and during sleep and before and after infusions of sodium lactate and a saline control. RESULTS: Panic disorder patients had higher oxygen saturations than comparison subjects before sleep onset and during sleep stages 0 and 2 before any infusions. The two groups did not differ on other respiratory variables and heart rate. Panic disorder patients responded to lactate infusions during stage 3-4 sleep with greater increases in heart rate and oxygen saturation, and possibly in respiratory rate and end-tidal PCO2, than comparison subjects. The saline control infusion had little effect. CONCLUSIONS: These findings suggest that panic disorder patients have greater cardiac and respiratory reactivity than healthy comparison subjects during sleep, when the influence of cognitive factors is minimal or absent.

High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder.

OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects.

Hypoventilation during sleep in children who have lymphoid airway obstruction treated by nasopharyngeal tube and T and A.

Three children with sleep apnea, alveolar hypoventilation, apparent mental retardation, and poor growth associated with chronically enlarged tonsils and adenoids were treated with the use of a nasopharyngeal tube followed by tonsillectomy and adenoidectomy. The effectiveness of this therapy was documented by polygraphic recording of sleep stages and respirations, and by correlation with serial arterial blood gases and pH. The nasopharyngeal tube was well tolerated, easy to use, and effective in diagnosis and treatment. We suggest that its use be further evaluated in patients with obstructive apnea.

Obstructive sleep apnea and its therapy: clinical and polysomnographic manifestations.

Obstructive sleep apnea syndrome was studied in 32 children, aged 2 to 14 years, in the sleep-wake disorders center at Montefiore Hospital and Medical Center during the years 1977 to 1980. All children underwent all-night polysomnograms; 17 of these children had surgery to relieve airway obstruction and seven had a repeat polysomnographic study 4 to 6 weeks following the surgery. There was a significant improvement in the number of obstructive apneas and in other apnea indices following surgery. There was no significant effect on the durations and the proportions of the various sleep stages, on sleep efficiency, or on the number of awakenings.

How should the multiple sleep latency test be analyzed?

Results of the multiple sleep latency test (MSLT) are commonly recorded as 4-5 latencies to sleep onset, together with their mean. The suitability of these and other MSLT measures of daytime sleep tendency was examined in 111 non-narcoleptic patients of a sleep disorders center. Sleep and breathing patterns had been recorded for one night, followed by a five-nap MSLT. It was found that MSLT latencies to sleep stages 1 and 2 were distributed non-normally. There was typically an excessive frequency of long latencies and a secondary peak at 20 minutes, the longest allowed latency. Wake efficiencies (WE) (100% time asleep) were similarly distributed. Mean sleep latencies (SL) and mean WE were generally distributed more normally than the corresponding medians. Regression analysis showed that the MSLT variables best predicted by sleep-disordered breathing during the previous night were those based on WE. Effects were greatest for the first 1-2 naps. Whether the 4- or 5-nap MSLT can be shortened will depend on corroborating data from other labs. For now, mean WE appears to be the best measure of daytime sleep tendency. Regardless of which MSLT measure is used, sleep-disordered breathing, nocturnal sleep time, age, and gender together explain less than one-fourth of the variance found in the non-narcoleptic patients of a sleep disorders center. Much daytime sleepiness therefore remains unexplained.

Regulation of sleep rate and circadian consolidation of sleep and wakefulness in an infant.

Observations of sleep and wakefulness were continuously made over an infant's first 6 months by Kleitman and Engelmann. Those data have been reanalyzed using a newly developed tool, fractional-time analysis, and two measures derived from it: 1) sleep rate, the rate at which the infant accumulated sleep; and 2) consolidation, the degree to which episodes of sleep and wakefulness were sustained and clustered. Changes in sleep rate and consolidation were independent and were attributed to separate underlying neural mechanisms. Consolidation increased over the 6-month course of development. This was explained by the development of circadian rhythmicity, which appeared during the 1st month as a free-running, endogenously generated rhythm in sleep-episode durations. Starting in the 2nd month, sleep rate was regulated, and it remained remarkably stable for weeks at a time. Sleep rate decreased over the 6-month period, perhaps because metabolic rate decreased as the infant grew. Short-term (weeks-long) changes in consolidation and sleep rate were explained by "beating" of the non-24-hour, endogenous sleep rhythm with direct effects of the 24-hour environment on sleep and wakefulness. Environmental stimuli eventually entrained the circadian pacemaker, bringing the consolidating periods of wakefulness and sleep into register with day and night. The infant was thereby efficiently exposed to periodic sensory and social stimuli, promoting normal neural development. A model of sleep-wake regulation based on independent mechanisms for circadian timing and sleep-wake regulation is proposed.

Eating and its relationships with subjective alertness and sleep in narcoleptic subjects living without temporal cues.

The sleep and meal patterns of normal subjects appear to be governed by a common timing mechanism. To investigate whether the postulated mechanism may be disordered in narcolepsy, a disorder of sleep timing, we analyzed the sleep, eating, and subjective alertness of six narcoleptic subjects and seven normal controls while they lived in a temporal isolation laboratory. When subjects were free to eat and sleep whenever they chose ("free-running"), the meal patterns and nutrient intakes of the free-running narcoleptic subjects and controls were similar; no evidence of an eating disorder intrinsic to narcolepsy was found. When meals were offered on a 24-h schedule, narcoleptic subjects ate more frequently than did the controls. In two of three narcoleptic subjects whose free-running biological days markedly lengthened, intermeal intervals lengthened proportionately. This was evidence that the timing of sleep (bed-dark) periods and meals was indeed governed by a common mechanism. Meal onsets of narcoleptic subjects were preceded by a 90-min period of decreased napping and, when meals were scheduled, by increased subjective alertness. They were followed by a 150-min period of increased napping and decreased subjective alertness. Postprandial deactivation was not found in controls. The deactivation could not be explained by a post-absorptive effect of food, since the contents of meals that were followed by naps did not differ from those that were not followed by naps. While a preabsorptive effect of meals has not been ruled out, we suggest that postmeal deactivation may be evidence that the mechanism that times sleep periods and meals also modulates the temporal pattern of narcoleptic naps.

Effects of flurazepam on sleep and growth hormone release during sleep in healthy subjects.

We studied the effect of flurazepam, a known suppressor of stages 3 and 4 of sleep, on nocturnal sleep patterns and on growth hormone release immediately following sleep onset in normal young adults. Polysomnography and sampling of growth hormone (every 20 min for 26 h) were performed before and after 2 weeks of nightly flurazepam (30 mg, 8 subjects) or placebo (8 subjects) administration. There were no significant changes in growth hormone release in spite of a significant decrease in stage 4 sleep (69%) and total waking time (46%) and an increase in total sleep time (23%) in the drug group. REM sleep was not changed. These results indicate that the normal GH release following sleep onset continues to occur despite stage 4 suppression by pharmacological means.

How accurately does wrist actigraphy identify the states of sleep and wakefulness?

STUDY OBJECTIVES: Because sleep and wakefulness differ from each other by the amount of body movement, it has been claimed that the two states can be accurately distinguished by wrist actigraphy. Our objective was to test this claim in lengthy polysomnographic (psg) and actigraphic (acf) samples that included night and day components. DESIGN: Fourteen healthy young (21-35 years) and old (70-72 years) men and women lived in a laboratory without temporal cues for 7 days. Each subject continuously wore sleep-recording electrodes as well as 2 wrist-movement recorders. Act measurements were converted to predictions of sleep and wakefulness by simple-threshold and multiple-regression methods. Psg served as the gold standard for calculation of predictive values (PV, the probability that an act prediction is correct by psg criteria). SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The 7-day act recordings showed clear circadian cycles of high and low activity that respectively corresponded to subjective days, when subjects were wakeful, and subjective nights when they slept. Lower act levels corresponded to deeper states of psg sleep. Logistic regression on a 20-minute moving average of act gave the highest overall PV's. Nevertheless, the mean PV for sleep (PVS) was only 62.2% in complete, day + night samples. PVS was 86.6% in night samples. Act successfully predicted wakefulness during subjective nights (PVW = 89.6) and accurately measured circadian period length and the extent of sleep-wake consolidation, but it overestimated sleep rate and sleep efficiency. Act systematically decreased before sleep onset and increased before awakening, but reliable transitions among joint psg/act states (the Markov-1 property) were not demonstrated. CONCLUSIONS: Low PV's and overestimation of sleep currently disqualify actigraphy as an accurate sleep-wake indicator. Actigraphy may, however, by useful for measuring circadian period and sleep-wake consolidation and has face validity as a measure of rest/activity.

Direct comparison of two widely used activity recorders.

Wrist actigraphy is increasingly used to track circadian rest-activity cycles and to identify states of wakefulness and sleep, yet the measurement characteristics of activity recorders have never been compared. Two widely used recorders are compared here: the MotionLogger from Ambulatory Monitoring, Inc (AM) and the Gaehwiler (G). They were worn together on the same wrist for periods averaging 41.5 hours by five members of a research team. Activity counts were stored every half-minute. Pairwise comparisons between recorders of each type showed both types to be reliable. Each also validly detected circadian rest/activity cycles. Both types suffered, however, from insensitivity. For the lower 75% of activity levels, the variance of data from the G was indeed so small as to be essentially uninformative. Since these levels include over 95% of all nocturnal data, the G must be less sensitive than the AM to small nocturnal movements, including those signifying arousal. An additional difference is that data from the AM but not the G were distributed in biphasic fashion. Biphasic activity levels are consistent with the common assumption that activity/wakefulness and rest/sleep are distinct neurobehavioral states. As the use of actigraphy increases, the important differences found here between two leading instruments point to an urgent need for standards by which activity recorders can be compared. Aspects of instrument design that could be quantitatively rated are reliability, validity, ruggedness and artifact rejection.

Cognitive and motor performance of narcoleptic and normal subjects living in temporal isolation.

Six unmedicated narcoleptic subjects and nine normal controls lived in a temporal isolation laboratory for 18-22 days. They were permitted to "free-run" for the last 9-13 days. Brief cognitive and motor performance tests were repeated on average six times per subjective day. They consisted of serial search, complex verbal reasoning tasks and manual dexterity of each hand. Only minor differences in performance were found between the narcoleptic subjects and controls. Narcoleptic subjects showed mild impairment of accuracy on the search task that could be explained by occasional lapses and an afternoon dip in performance. Narcoleptic subjects also tended to perform some tasks more slowly, but the group differences were not significant. Neither speed nor accuracy of performance of narcoleptic subjects decreased over the course of the experiment. By one standard of performance, therefore, all or nearly all of the sleep need of these subjects was met by the sleep they obtained in the laboratory. That amount, in turn, did not exceed the total sleep obtained by the normal controls. Significant time-of-day effects were found in narcoleptic subjects for speed of verbal reasoning (progressive slowing over the course of the day), manual dexterity (fluctuations in speeds) and accuracy of serial search (afternoon dip). These variations in performance could not be attributed to changes in core body temperature or to occurrences of naps or meals.

Long-term ambulatory temperature monitoring in a subject with a hypernychthemeral sleep--wake cycle disturbance.

A portable temperature data logger was used for prolonged rectal temperature monitoring in an ambulatory subject with a longer than 24 hr (hypernychthemeral) sleep-wake cycle. The mean period of the sleep-wake and circadian temperature cycles was 24.8 hr. However, the period of the sleep-wake cycle fluctuated considerably, being less than 24.8 hr when he slept during the socially desirable sleep hours and more than 24.8 hr when he slept during the day. In the first instance, the daily temperature fall occurred later than, and in the second earlier than, sleep onset. During the times of desynchronization of the two cycles, he complained of insomnia, fatigue, and reduced performance. We postulate that his hypernychthemeral cycles were the result of either a primary defect in the mechanism of entrainment or "weakened" social zeitgebers due to a personality disorder. These concepts are supported by a sleep-wake pattern resembling that of relative coordination. We therefore raise the possibility that 24 hr was beyond the range of entrainment of the subject's circadian temperature cycle during the study.

Age-related differences in recovery from simulated jet lag.

Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

Circadian rest-activity rhythms in demented and nondemented older community residents and their caregivers.

OBJECTIVE: Disruptive nocturnal behaviors (DNBs) of older people often threaten the caregiving arrangements on which their community tenure depends. Dementing disorders are especially prone to result in disrupted sleep and agitated behaviors ("sundowning"). The objective here was to develop an objective correlate of DNBs, by which their severity and effects on caregivers can be measured. DESIGN: Quantitative comparison of subjective sleep and motor activity patterns in older people and their caregivers. It was hypothesized that older people with reported DNBs would be more motorically active at night than their caregivers. SETTING: Subjects' homes. PARTICIPANTS: Twenty-five demented and 18 nondemented older day-care participants and their paired caregivers. MEASUREMENTS: Older subjects and caregivers simultaneously kept daily sleep logs and recorded wrist motor activity every .5 minute for 9 days. A novel method was devised to identify and exclude from analysis periods when the activity monitor was not being worn. Such periods were common. Activity data were analyzed by computing hourly means and by fitting cosine models by least squares. RESULTS: Demented older people were not significantly more active at night than their caregivers, though group differences varied by time of night. They were significantly less active in the daytime than were their caregivers. Nondemented older people were significantly more active at night than their caregivers and were as active by day as their caregivers. The caregivers of demented and nondemented older people had similar rest-activity patterns. The mean amplitudes of cosine models were smaller in the older adults. Acrophases (peaks) fell between 2 and 3 pm and did not differ significantly among the groups. CONCLUSIONS: As a result of increased nighttime motor activity and decreased daytime activity, rest-activity rhythms were flatter in older adults than in caregivers. This was not explained fully by age and does not necessarily imply that the output of a circadian pacemaker was low. Decreased daytime activity may have resulted from deficient physical stimulation or frailty. Frailty may also explain why nighttime activity was not more elevated in the demented older people. Increased nighttime activity is probably explained by depression, sleep-schedule disturbances, restless legs, or other sleep disorders. Judging by their shared variations of activity, caregivers interacted mainly with the demented older people at bedtime and at rising time in the morning.

Impaired nocturnal erections and impotence following transurethral prostatectomy.

A case of impotence with significantly impaired nocturnal penile tumescence (NPT) following transurethral resection of the prostate (TURP) is described. The patient was studied with polysomnographic recording including measurements of NPT for three consecutive nights at nine months after surgery and showed a total absence of full erections. Possible causes of his impotence are discussed. It is concluded that the total clinical picture strongly suggests that the erectile dysfunction was a result of physiologic complications of the surgery. Methodologic problems in past work are discussed, and the need for detailed diagnostic studies is stressed. The sleep studies that should be a part of this comprehensive evaluation are described.

The effect of desynchronization on meal patterns of humans living in time isolation.

We analyzed the timing of meals in nine subjects who lived for several weeks in a time isolation environment and whose free-running sleep-wake cycles lengthened markedly and lost synchrony with the body temperature rhythm for part of the study. The long sleep-wake periods (SWP) in free-running desynchrony (mean = 34 +/- 3 hours) as compared to free-running synchrony (25 +/- 1 hours) enabled us to compare meal timing in two distinct temporal frameworks and to relate them to the two major oscillators presumed to underlie circadian rhythms in man. We found that when the SWP lengthened in desynchrony, the intermeal interval (IMI) increased significantly. In half the subjects, the increase in IMI was approximately proportional to the increase in the SWP--the IMI "stretched" along with the SWP. Analysis of prelunch and postlunch IMIs indicated that the lengthening of the IMI during desynchrony was comparable in early and later parts of the subjective day. The increase in meal spacing was not due to increased caloric content of meals. The findings support an interpretation of dual regulation of meal timing. Proportional increases in IMI and SWP suggest that the mechanism governing the timing of the sleep-wake cycle also governs meal timing. The less than proportional increase in some cases suggests that an additional, probably metabolic, mechanism tends to limit the intervals between meals.

Meal size and intermeal interval in human subjects in time isolation.

We analyzed the content and number of meals eaten by eight subjects who lived for several weeks in time isolation and whose free-running sleep-wake periods (SWP) lengthened (to an average of more than 33 hours) and were desynchronized from the stable 25 hour rhythm of body temperature. Recently, in an analysis of meal timing, we reported that the long SWPs of free-running desynchrony (FRD) were associated with significantly longer intermeal intervals (IMI) than the shorter SWPs of free-running synchrony (FRS), suggesting that meals and sleep-wake events are timed by the same mechanism. We now report that in both FRS and FRD, subjects ate approximately three meals per SWP and the average size of a meal was similar across conditions. As a result, mean caloric intake decreased by 21 percent per 24 hours and mean satiety ratio increased by 27 percent on the long biological days of FRD. Despite the decrease in caloric intake, body weight did not change significantly in FRD compared to FRS. Decreased food consumption in FRD was not attributable to lowered core body temperature. The similarity of average meal size in the two FR conditions suggested that increased meal size did not drive the longer IMIs of desynchrony, although variability of caloric intake from meal to meal within conditions correlated with postmeal and premeal intervals. The results are interpreted as further support for the concept that in time isolation, the same mechanisms that governs the timing of sleep and waking is important in regulating the timing of meals.

Blood glucose prior to meal request in humans isolated from all temporal cues.

The factors responsible for meal initiation in man are not known. Recently, a small, transient decline in blood glucose was found to precede meals in freely feeding rats (1). To determine whether a similar decline in blood glucose precedes meals in humans, we measured plasma glucose concentration before and after requests for lunch on 4 different days in each of 7 subjects living in a setting that eliminated temporal cues and most or all external prompts for eating. Under these conditions, subjects could request any meal at any time by naming it and specifying its content. Meals were promptly prepared and served. Blood was sampled at randomized intervals averaging 20 minutes. Blood samples from 120 minutes preceding the subject's request for lunch to 90 minutes after the request were analyzed for glucose by the hexokinase method. The mean plasma glucose concentration did not change significantly from about 1 hour before lunch request to 20-30 minutes after the request. A transient decline in glucose similar to that reported in the rat was observed prior to only 1 of the 28 lunches. Given the ease of obtaining food and the absence of the usual temporal and psychosocial cues for eating, the results are not consistent with the hypothesis that meal requests in humans are triggered by a transient decline of plasma glucose concentration. The hypothesis is not disproven, however, since the intersample intervals of about 20 minutes may have failed to detect decreases of blood glucose that were smaller or of shorter duration than those of the rat.