Jeffrey A. Elliott

Entrainment of Circadian Programs

Of the three defining properties of circadian rhythmicity—persisting free‐running rhythm, temperature compensation, and entrainment—the last is often poorly understood by many chronobiologists. This paper gives an overview of entrainment. Where have we been? Where are we now? Whence should we be going? Particular emphasis is given to a discussion of the Discrete vs. Continuous models for entrainment. We provide an integrated mechanism for entrainment from a limit‐cycle perspective.

Sleep estimation from wrist movement quantified by different actigraphic modalities

Progress in transducer design and empirical characterization of wrist movement has led to diverse wrist activity monitors, each with its unique features and modality of operation. This study compared sleep--wake estimates from nocturnal wrist activity quantified by different motion-quantifying algorithms. Healthy young adults wore an Actillume and a Mini Motionlogger on the same wrist while nocturnal polysomnography data were recorded simultaneously in the laboratory. Activity data were analyzed with ACTION3 using scoring algorithms independently calibrated for each measurement modality. Overall, each modality yielded accurate and reliable sleep estimates relative to polysomnographic estimates (agreement rates: 91.4--96.5%, correlations for sleep duration: 0.79--0.94). Estimates derived from Actillume modalities were comparable to those of Mini Motionloggers, suggesting that the transducers of these two devices performed comparably for monitoring sleep and wakefulness. Wrist movement quantified by the Mini Motionlogger proportional-integrating mode yielded the best accuracy for detection of sleep--wake states.

Age-related changes of circadian rhythms and sleep-wake cycles

OBJECTIVES: To compare relationships between the sleep‐wake cycle and endogenous circadian rhythms in young and older adults and to examine correlates between evening naps and circadian rhythms in older adults.

Mortality related to actigraphic long and short sleep.

BACKGROUND The folk belief that we should sleep 8 h seems to be incorrect. Numerous studies have shown that self-reported sleep longer than 7.5 h or shorter than 6.5 h predicts increased mortality risk. This study examined if prospectively-determined objective sleep duration, as estimated by wrist actigraphy, was associated with mortality risks. METHODS From 1995-1999, women averaging 67.6 years of age provided one-week actigraphic recordings. Survival could be estimated from follow-up continuing until 2009 for 444 of the women, with an average of 10.5 years before censoring. Multivariate age-stratified Cox regression models were controlled for history of hypertension, diabetes, myocardial infarction, cancer, and major depression. RESULTS Adjusted survival functions estimated 61% survival (54-69%, 95% C.I.) for those with sleep less than 300 min and 78% survival (73-85%, 95% C.I.) for those with actigraphic sleep longer than 390 min, as compared with survival of 90% (85-94%, 95% C.I.) for those with sleep of 300-390 min. Time-in-bed, sleep efficiency and the timing of melatonin metabolite excretion were also significant mortality risk factors. CONCLUSION This study confirms a U-shaped relationship between survival and actigraphically measured sleep durations, with the optimal objective sleep duration being shorter than the self-report optimums. People who sleep five or six hours may be reassured. Further studies are needed to identify any modifiable factors for this mortality and possible approaches to prevention.

Actigraphy suggests age-related differences in napping and nocturnal sleep

The aim of this study was to contrast the time distribution of out‐of‐bed napping in young and older adults through recordings of wrist activity, and to evaluate the correlates of napping with nocturnal sleep. Seventy‐three young adults between 18 and 32 years and 60 older adults between 60 and 75 years of age participated in the study. Subjects were selected for good general health and had few sleep complaints. They wore wrist‐activity monitors and kept daily sleep logs for 1 week. Automatic sleep scoring was edited by the authors, supplemented by sleep logs and illumination data as well as activity data. Napping episodes were modestly increased in older adults, but there was no difference in the daily duration of napping. Older adults napped more in the evening (especially within 2 h before bedtime), whereas young adults napped more in the afternoon. The older adults with evening naps (n = 31) showed earlier nocturnal wake‐up times and decreased nocturnal sleep duration compared with the older adults without evening naps (n = 29). There was no difference in nocturnal sleep between young adults with afternoon naps (n = 32) and without afternoon naps (n = 41). In determining the effects of napping on nocturnal sleep, timing of napping and age are important. Maintaining alertness during the evening (e.g. by bright light exposure or moderate exercise) would be a possible approach to delay wake‐up times in older adults.

Depression and endogenous melatonin in postmenopausal women

BACKGROUND Previous reports on melatonin secretion in depression are numerous but conflicting. There are very few studies relating the duration of the nocturnal melatonin peak to depression, and the results of those studies have been equivocal. METHODS We studied mood disorders and urinary melatonin excretion in 382 postmenopausal women. Psychiatric diagnoses and global assessment of functioning (GAF) scores were determined based on a Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Urinary 6-sulfatoxymelatonin (6-SMT) samples were collected for two 24-h periods at home. RESULTS A positive family history of depression was significantly related to a longer duration of 6-SMT excretion. There were marginally significant associations between current major depression and delayed offset of 6-SMT excretion and between later acrophase and lifetime major depression, even with control for age, ethnicity, season, and several medications. LIMITATIONS The subjects were studied in their home environments, where light effects were not controlled. Data were restricted to postmenopausal women, including a limited number of subjects with current major depression. CONCLUSIONS These results suggest that there might be a familial vulnerability in the endogenous melatonin signal in subjects prone to depression, and an abnormality in the duration of the melatonin signal in those with current major depression.

Circadian abnormalities in older adults

This study examined the circadian phase adjustment of symptomatic elders ages 60–79 years in comparison with that of young, healthy adults ages 20–40 years. Seventy‐two elders with complaints of insomnia or depression, and 30 young, healthy adults were assessed for 5–7 days at home. Sleep and illumination were recorded with Actillume wrist monitors and sleep diaries. Urine was collected over two 24‐hr periods and assayed for 6‐sulphatoxymelatonin (6‐smt). The volunteers were then observed continuously for 5 nights and 4 days in the laboratory. In the laboratory, sleep periods were fixed at 8 hr with polysomnographic assessment of sleep, apnea‐hypopnea, and nocturnal myoclonus. Circadian dispersion, defined as the mean variation of 6‐smt acrophase from the median age‐specific acrophase, was significantly greater in the older vs. young adults. Likewise, circadian malsynchronization, defined as the absolute number of hours (advance or delay) between the 6‐smt acrophase and the middle of the sleep period, was significantly greater in the older vs. young volunteers. For the older volunteers, multiple regressions were calculated associating sleep with potential correlates of sleep disturbance. Nocturnal myoclonus and circadian malsynchronization were more strongly associated with sleep impairment than other factors (e.g., sleep apnea, depression). These observations suggest that circadian malsynchronization might be a common and significant cause of disturbed sleep among adults over age 60.

Bright-Light Mask Treatment of Delayed Sleep Phase Syndrome

We treated delayed sleep phase syndrome (DSPS) with an illuminated mask that provides light through closed eyelids during sleep. Volunteers received either bright white light (2,700 lux, n = 28) or dim red light placebo (0.1 lux, n = 26) for 26 days at home. Mask lights were turned on (< 0.01 lux) 4 h before arising, ramped up for 1 h, and remained on at full brightness until arising. Volunteers also attempted to systematically advance sleep time, avoid naps, and avoid evening bright light. The light mask was well tolerated and produced little sleep disturbance. The acrophase of urinary 6-sulphatoxymelatonin (6-SMT) excretion advanced significantly from baseline in the bright group (p < 0.0006) and not in the dim group, but final phases were not significantly earlier in the bright group (ANCOVA ns). Bright treatment did produce significantly earlier phases, however, among volunteers whose baseline 6-SMT acrophase was later than the median of 0602 h (bright shift: 0732-0554 h, p < 0.0009; dim shift: 0746-0717 h, ns; ANCOVA p = 0.03). In this subgroup, sleep onset advanced significantly only with bright but not dim treatment (sleep onset shift: bright 0306-0145 h, p < 0.0002; dim 0229-0211 h, ns; ANCOVA p < .05). Despite equal expectations at baseline, participants rated bright treatment as more effective than dim treatment (p < 0.04). We conclude that bright-light mask treatment advances circadian phase and provides clinical benefit in DSPS individuals whose initial circadian delay is relatively severe.

Circadian Phase in Adults of Contrasting Ages

There is evidence that aging may impair phase‐shifting responses to light synchronizers, which could lead to disturbed or malsynchronized circadian rhythms. To explore this hypothesis, 62 elder participants (age, 58 to 84 years) and 25 young adults (age, 19 to 40 years) were studied, first with baseline 1‐wk wrist actigraphy at home and then by 72 h in‐laboratory study using an ultra‐short sleep‐wake cycle. Subjects were awake for 60 minutes in 50 lux followed by 30 minutes of darkness for sleep. Saliva samples were collected for melatonin, and urine samples were collected for aMT6s (a urinary metabolite of melatonin) and free cortisol every 90 minutes. Oral temperatures were also measured every 90 minutes. The timing of the circadian rhythms was not significantly more variable among the elders. The times of lights‐out and wake‐up at home and urinary free cortisol occurred earlier among elders, but the acrophases (cosinor analysis‐derived peak time) of the circadian rhythm of salivary melatonin, urinary aMT6s, and oral temperature were not significantly phase‐advanced among elders. The estimated duration of melatonin secretion was 9.9 h among elders and 8.4 h among young adults (p<0.025), though the estimated half‐life of blood melatonin was shorter among elders (p<0.025), and young adults had higher saliva melatonin and urinary aMT6s levels. In summary, there was no evidence for circadian desynchronization associated with aging, but there was evidence of some rearrangement of the internal phase‐angles among the studied circadian rhythms.

Ethnicity, sleep, mood, and illumination in postmenopausal women

BackgroundThis study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms.MethodsIn an ancillary study to the Womens Health Initiative, 459 postmenopausal women were recorded for one week in their homes, using wrist monitors. Sleep and illumination experience were estimated. Depression was self-rated with a brief adjective check list. Affective diagnoses were made using the SCID interview. Sleep disordered breathing was monitored with home pulse oximetry.ResultsHispanic and African-American women slept less than European-American women, according to both objective recordings and their own sleep logs. Non-European-American women had more blood oxygen desaturations during sleep, which accounted for 26% of sleep duration variance associated with ethnicity. Hispanic women were much more depressed. Hispanic, African-American and Native-American women experienced less daily illumination. Less daily illumination experience was associated with poorer global functioning, longer but more disturbed sleep, and more depression.ConclusionsCurtailed sleep and poor mood were related to ethnicity. Sleep disordered breathing was a factor in the curtailed sleep of minority women. Less illumination was experienced by non-European-American women, but illumination accounted for little of the contrasts between ethnic groups in sleep and mood. Social factors may be involved.