Earlier Circadian Phase Research Articles

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak V̇o2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak V̇o2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak V̇o2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak V̇o2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Sleep and circadian differences between light and heavy adult alcohol drinkers.

BackgroundNumerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post‐illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers.MethodsParticipants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8‐day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9‐h laboratory session with a photoreceptor responsivity and circadian phase assessment.ResultsThe heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO‐midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = −0.01, p = 0.94).ConclusionsThese results are consistent with earlier reports of more eveningness and a shorter DLMO‐midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

0638 Circadian rhythms among youth with craniopharyngioma

Abstract Introduction Craniopharyngioma is an intracranial tumor located in the hypothalamic and pituitary region. Despite high survival rates for youth with craniopharyngioma, quality of life is substantially affected. Morbidity includes high rates of sleep disruption, particularly disorders of hypersomnolence. Circadian rhythms may also be affected due to the proximity of the tumor and subsequent treatment to the hypothalamic-pituitary-adrenal axis, though the role of circadian rhythms has been less studied in this patient population. To evaluate circadian rhythms among youth with craniopharyngioma, dim light melatonin onset (DLMO), an established marker of the circadian system, was estimated. Methods Fifty-five patients between the ages of 7 and 20 years participated in this study. Data were collected prior to completion of proton therapy (if indicated). Participants provided hourly saliva samples, in their homes, starting 3 hours prior to habitual bedtime until 1 hour following in dim light conditions (&amp;lt;30 lux). DLMO was calculated based on a threshold of 4 pg/ml. Participants also wore actigraphs to measure sleep patterns. We derived bedtime and waketime from actigraphy and calculated phase angles to bedtime and waketime. DLMO timing and phase angles were compared to published norms for healthy youth ages 9 to 17 years. Results DLMO could not be estimated for almost half of the sample (n=25), most often due to a melatonin value above the threshold at the first collection time point. Higher grade of hypothalamic involvement and the presence of diabetes insipidus predicted inability to capture DLMO. Subsample analyses of participants with DLMO (n=30) showed later DLMO timing and shorter phase interval to bedtime than the healthy reference sample. Conclusion With standard practice for DLMO estimation, we only obtained estimates for slightly more than half our sample. This may reflect circadian rhythm disturbances or advanced circadian phase. Relative to published norms, those with captured DLMO had later DLMO timing and shorter phase angles to bedtime, indicating sleep at an earlier circadian phase. These findings suggest possible circadian rhythm disruption in pediatric craniopharyngioma. Methodological differences among samples may also contribute to findings. Further examination of circadian rhythm disruption and relations with other sleep disturbances is needed. Support (If Any) This work was supported by the Cancer Center Support Grant (CA21765) from the National Cancer Institute and ALSAC.

Early chronotype with advanced activity rhythms and dim light melatonin onset in a rural population.

Studying communities at different stages of urbanisation and industrialisation can teach us how timing and intensity of light affect the circadian clock under real-life conditions. We have previously described a strong tendency towards morningness in the Baependi Heart Study, located in a small rural town in Brazil. Here, we tested the hypothesis that this morningness tendency is associated with early circadian phase based on objective measurements (as determined by dim light melatonin onset, DLMO, and activity) and light exposure. We also analysed how well the previously collected chronotype questionnaire data were able to predict these DLMO values. The average DLMO observed in 73 participants (40 female) was 20:03±01:21, SD, with an earlier average onset in men (19:38±01:16) than in women (20:24±01:21; P≤.01). However, men presented larger phase angle between DLMO and sleep onset time as measured by actigraphy (4.11hours vs 3.16hours; P≤.01). Correlational analysis indicated associations between light exposure, activity rhythms and DLMO, such that early DLMO was observed in participants with higher exposure to light, higher activity and earlier light exposure. The strongest significant predictor of DLMO was morningness-eveningness questionnaire (MEQ) (beta=-0.35, P≤.05), followed by age (beta = -0.47, P≤.01). Sex, light exposure and variables derived from the Munich chronotype questionnaire were not significant predictors. Our observations demonstrate that both early sleep patterns and earlier circadian phase have been retained in this small rural town in spite of availability of electrification, in contrast to metropolitan postindustrial areas.

Circadian Phase and Phase Angle Disorders in Primary Insomnia.

We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia. We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days. Circadian phase was assessed from salivary dim light melatonin onset (DLMO) time during a 12-hour laboratory visit. Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46 females, 35.5 ± 12.3 years [M ± SD]) and 21 controls (14 females, 34.4 ± 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 hours vs. 24:13 ± 1:30 hours, respectively; p = .84) but had a later average DLMO times (20:56 ± 1:55 hours, 18:17-01:21 vs. 22:02 ± 2:02 hours, 17:11-04:52, respectively; p = .04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 hours (± 1:43) vs. 3:10 hours (± 1:08), respectively; p = .008), of whom 10% tried to sleep at or before DLMO (compared to 0 controls), and 22% tried to sleep before or within 1 hour after DLMO (compared to 6% of controls). A substantial proportion (10%-22%) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.

Impact of sleep inertia on visual selective attention for rare targets and the influence of chronotype.

Sleep inertia is affected by circadian phase, with worse performance upon awakening from sleep during the biological night than biological day. Visual search/selective visual attention performance is known to be sensitive to sleep inertia and circadian phase. Individual differences exist in the circadian timing of habitual wake time, which may contribute to individual differences in sleep inertia. Because later chronotypes awaken at an earlier circadian phase, we hypothesized that later chronotypes would have worse visual search performance during sleep inertia than earlier chronotypes if awakened at habitual wake time. We analysedperformance from 18 healthy participants [five females (22.1±3.7years; mean±SD)] at ~1, 10, 20, 30, 40 and 60min following electroencephalogram-verified awakening from an 8h in-laboratory sleep opportunity. Cognitive throughput and reaction times of correct responses were impaired by sleep inertia and took ~10-30min to improve after awakening. Regardless whether chronotype was defined by dim light melatonin onset or mid-sleep clock hour on free days, derived from the Munich ChronoType Questionnaire, the duration of sleep inertia for cognitive throughput and reaction times was longer for later chronotypes (n=7) compared with earlier chronotypes (n=7). Specifically, performance for earlier chronotypes showed significant improvement within ~10-20min after awakening, whereas performance for later chronotypes took ~30min or longer to show significant improvement (P<0.05). Findings have implications for decision making immediately upon awakening from sleep, and are consistent with circadian theory suggesting that sleep inertia contributes to longer-lasting impairments in morning performance in later chronotypes.

Shift Work and Cognitive Flexibility: Decomposing Task Performance.

Deficits in cognitive functioning associated with shift work are particularly relevant to occupational performance; however, few studies have examined how cognitive functioning is associated with specific components of shift work. This observational study examined how circadian phase, nocturnal sleepiness, and daytime insomnia in a sample of shift workers ( N = 30) were associated with cognitive flexibility during the night shift. Cognitive flexibility was measured using a computerized task-switching paradigm, which produces 2 indexes of flexibility: switch cost and set inhibition. Switch cost represents the additional cognitive effort required in switching to a different task and can impact performance when multitasking is involved. Set inhibition is the efficiency in returning to previously completed tasks and represents the degree of cognitive perseveration, which can lead to reduced accuracy. Circadian phase was measured via melatonin assays, nocturnal sleepiness was assessed using the Multiple Sleep Latency Test, and daytime insomnia was assessed using the Insomnia Severity Index. Results indicated that those with an earlier circadian phase, insomnia, and sleepiness exhibited reduced cognitive flexibility; however, specific components of cognitive flexibility were differentially associated with circadian phase, insomnia, and sleepiness. Individuals with an earlier circadian phase (thus more misaligned to the night shift) exhibited larger switch costs, which was also associated with reduced task efficiency. Shift workers with more daytime insomnia demonstrated difficulties with cognitive inhibition, whereas nocturnal sleepiness was associated with difficulties in reactivating previous tasks. Deficits in set inhibition were also related to reduced accuracy and increased perseverative errors. Together, this study indicates that task performance deficits in shift work are complex and are variably impacted by different mechanisms. Future research may examine phenotypic differences in shift work and the associated consequences. Results also suggest that fatigue risk management strategies may benefit from increased scope and specificity in assessment of sleep, sleepiness, and circadian rhythms in shift workers.

Constraint is associated with earlier circadian phase and morningness: Confirmation of relationships between personality and circadian phase using a constant routine protocol

Associations amongst personality, diurnal preference, and circadian phase were investigated using a constant routine laboratory protocol. One hundred and sixty-eight healthy participants aged 18–30years (Women n=68) completed either a 30- or 50-hour constant routine under dim-light conditions (<3lx), during which circadian phase was measured from core body temperature and melatonin. Prior to laboratory admission, self-report measures of personality and diurnal preference were also obtained. The personality trait of Constraint correlated positively with morning diurnal preference and earlier circadian phase, with circadian phase partially mediating the relationship between Constraint and diurnal preference. No other personality variables correlated with circadian phase. Sex was an important covariate in several of the relationships investigated due to lower levels of Constraint and later CBT phase amongst men and was thus controlled for in all relevant analyses. Findings from this highly controlled study are consistent with previous field research in suggesting that earlier circadian phase is associated with the personality trait of Constraint.

Gender Difference in Timing of Nocturnal Rise of Subjective Sleepiness

Abstract. Experimental research of diurnal variations in body temperature and melatonin secretion consistently revealed an earlier entrained circadian phase in women than in men. Since it is well documented that daily fluctuations in self-reported level of sleepiness closely follow the circadian rhythms of melatonin and body temperature, one can predict that gender differences in phase characteristics of the 24-hour fluctuations of subjective sleepiness resemble the differences revealed by research of physiological and hormonal rhythms. Analysis of sleepiness self-scored by 46 male and 54 female participants of sleep deprivation experiments showed that female participants scored significantly higher their midnight sleepiness level. The model-based simulations of sleepiness curves confirmed the prediction of a relatively earlier phase of 24-hour oscillations of sleepiness in women. Such gender differences persisted after accounting for individual variation in habitual sleep times and morning-evening preference. In today’s environment, the earlier circadian phase in women can cause a larger delaying phase shift in response to midnight exposure to artificial light, but, on the other hand, the earlier rise of subjective sleepiness can make them less vulnerable to the delaying shifts.

Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase.

Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation.

Interlinks between sleep and metabolism

Interlinks between sleep and metabolism

Sleep inertia varies with circadian phase and sleep stage in older adults.

The purpose of our analysis was to determine if older adults show sleep inertia effects on performance at scheduled wake time, and whether these effects depend on circadian phase or sleep stage at awakening. Using the Digit Symbol Substitution Test, effects of sleep inertia on performance were assessed over the first 30 min after wake time on baseline days and when sleep was scheduled at different circadian phases. Mixed model analyses revealed that performance improved as time awake increased; that beginning levels of performance were poorest when wake time was scheduled to occur during the biological night; and that effects of sleep inertia on performance during the biological night were greater when awaking from non-REM (NREM) sleep than from REM sleep. Based on our current understanding of sleep inertia effects in young subjects, and previous reports that older subjects awaken at an earlier circadian phase and are more likely to have their final awakening from NREM sleep than younger adults, our findings suggest older adults may be more vulnerable to sleep inertia effects than young adults.