Multilevel modeling of chronotype and weekdays versus weekends to predict nonrestorative sleep

Nonrestorative sleep, a form of subjective sleep disturbance that has been largely neglected in the literature, is newly accessible to researchers via the validated restorative sleep questionnaire (RSQ). The daily version of the RSQ allows for analysis of within-subjects variation in restorative sleep across repeated samplings, and such day-to-day regularity in sleep variables has been highlighted as an important new direction for research. The present study used a sophisticated statistical approach, multilevel modeling, to examine the contributions of circadian chronotype, calendar day of questionnaire completion (weekends versus weekdays), and their interaction in explaining both interindividual and intraindividual variance in restorative sleep. Analyses were conducted using an archival dataset of college undergraduates who continuously completed daily RSQs over a 14-day sampling period. In the final multilevel model, possessing an evening type predicted lower restorative sleep between subjects, while sampling on weekdays predicted lower restorative sleep within subjects. Furthermore, a cross-level interaction was observed, such that the difference in restorative sleep on weekends versus weekdays was more pronounced among those with greater evening circadian preference. All of the effects were maintained after accounting for the significant influence of gender (women had less restorative sleep than men). These results are theoretically consistent with findings that evening types display stronger disparities in sleep schedules across free and workdays (i.e., social jet lag), and attest to the usefulness of multilevel models for statistically investigating how stable traits interact with factors that vary day to day (e.g., work or school schedules) in influencing sleep outcomes.     

Association of Eveningness With Problem Behavior in Children: A Mediating Role of Impaired Sleep

Eveningness, the preference of being active during the evening in contrast to the morning, has been associated with markedly increased problem behavior in adolescents; however, the underlying mechanisms are still not understood. This study investigates the association of eveningness with behavior and cognition in children aged 7–12 yrs, and explores the potential mediating role of a variety of sleep factors. Parents of 333 school-aged children (mean age?=?9.97 yrs; 55% girls) completed a sleep log and several questionnaires regarding eveningness, sleep habits, and behavioral problems. Intellectual abilities, working memory, and attention were assessed using the short-form of the Wechsler Intelligence Scale for Children (WISC) and subtasks of the Amsterdam Neuropsychological Tasks. Results showed that eveningness predicted behavioral problems over and above the effects of demographic variables (age, sex, and familial socioeconomic status) (p?=?0.003). Significant partial correlation was found for eveningness and sleep duration during weekdays (p?=?0.005), and not during weekends. Furthermore, evening orientation was associated with a reduced rested feeling on weekday mornings (p?<?0.001), but not on weekends. The most important sleep characteristic showing association with many cognitive and behavioral measures was the subjective feeling upon awakening—particularly during weekdays. Bootstrap mediation analyses demonstrated that sleep significantly mediated the effects of eveningness on behavioral problems, working memory, and sustained attention. Interestingly, mediation was only significant through the subjective feeling upon awakening on weekdays. The current findings indicate that the subjective feeling upon awakening is a much better predictor of daytime problems than subjective sleep quantity. Furthermore, the data suggest that negative outcomes in evening types are due to the fact that they wake up before their circadian drive for arousal and prior to complete dissipation of sleep pressure during weekdays. Interventions that target the misalignment of endogenous circadian rhythms and imposed rhythms are discussed. (Author correspondence: kbheijden@fsw.leidenuniv.nl)     

Health-Related Quality of Life in Adolescent Chronotypes—A Model for the Effects of Sleep Problems,Sleep-Related Cognitions,and Self-efficacy

In adolescence, the circadian preference shifts toward eveningness orientation. Eveningness seems to be negatively correlated with quality of life. The present study investigates influencing factors of this association and proposes a model for the mediating effects of sleep, sleep-related cognitions, and self-efficacy according to chronotype. The sample comprised N?=?280 adolescents (172 girls) aged 14–16 yrs (mean?=?15.19, SD?=?.76). Circadian preference, health-related quality of life (HRQoL), sleep disturbances, sleep-related dysfunctional cognitions, and general perceived self-efficacy were assessed online. Morning-orientated adolescents reported significantly higher HRQoL and less insomnia symptoms compared with evening-oriented chronotypes. In the total sample, insomnia symptoms mediated the relationship of chronotype and HRQoL. The strongest predictor of HRQoL in evening types was the degree of sleep-related dysfunctional cognitions. HRQoL in morning types was most strongly predicted by general self-efficacy, i.e., the global confidence in coping abilities. The findings support a negative relationship of eveningness and HRQoL in adolescents. Insomnia symptoms were identified to be mediating factors in this relationship. The influence of the mediating factors on HRQoL differed between morning and evening types. The model provides implications of how to enhance HRQoL in adolescents according to their circadian preference. (Author correspondence: karolin.roeser@uni-wuerzburg.de)     

Is self-reported morbidity related to the circadian clock?

Morningness and eveningness preference, an endogenous component of the circadian clock, is characterized by an interindividual difference in circadian phase and requires of humans a specific timing of behavior. The biological rhythms of morning and evening types are consequently phase shifted with fixed socioeconomic constraints. The impact of this phase shift on health is widely debated. The purpose of the authors' study was to determine the influence of morningness/eveningness preference on self-reported morbidity and health in an active population. A total of 1165 nonshift workers of the French national electrical and gas company, enrolled in the GAZEL cohort and aged 51.3+/-3.3 years, were included in this study. They replied by mail with a completed questionnaire, including morningness/eveningness preference, self-reported morbidity, subjective sleep patterns, and daytime somnolence and sleeping schedules for 3 weeks, during the spring of 1997. Annual self-reported health impairments were assessed with the annual general questionnaire of the GAZEL cohort for 1997. After adjustment for age, sex, and occupational status, morningness-like and eveningness-like participants reported a specific worse self-reported morbidity. Whereas morningness was associated with worse sleep (p = 0.0001), eveningness was associated with feeling less energetic (p = 0.04) and physical mobility (p = 0.02). These relationships were observed even in good sleepers, except for physical mobility. After adjustment for confounding variables, eveningness-like participants reported more sleep (p = 0.0004) and mood (p = 0.00018) disorders than morningness-like participants. Morningness/eveningness preference was related to specific chronic complaints of insomnia: morningness was related with difficulty in maintaining sleep (p = 0.0005) and the impossibility to return to sleep in the early morning (p = 0.0001) (sleep phase-advance syndrome); eveningness was related to difficulty in initiating sleep (p = 0.0001) and morning sleepiness (p = 0.0001). In good sleepers, morningness was related with sleep phase-advance syndrome (p = 0.0001) and eveningness with morning sleepiness (p = 0.0001). In conclusion, the expression (phase advance or delay) of the circadian clock could be related to worse self-reported morbidity and health. These findings must be verified by further epidemiological studies, but they suggest that the impossibility to return to sleep in the early morning is not only associated with age.     

Chronotype and its relationship with sleep disorders in children with attention deficit hyperactivity disorder

Chronotype can be classified as morningness types, people who prefer morning hours for their physical and mental activities; eveningness types, people who prefer the afternoon or evening hours; and intermediate types, those who show characteristics of both morningness and eveningness types. Attention deficit hyperactivity disorder (ADHD) has been linked with disturbances in chronotype, particularly increased eveningness. Despite the possibility of an association between chronotypes, sleep disturbances and ADHD symptoms, there is little evidence of this association considering the child population. The purpose of this study was to examine chronotype preferences in children aged between 7 and 12 years who were diagnosed as having ADHD in the context of sleep disturbances. The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version, Conner’s Rating Scales, Children’s Sleep Habit Questionnaire and Children’s Chronotype Questionnaire were used for the evaluation of children with ADHD and healthy controls. The ADHD group was 73% combined-type, and the eveningness scores of the ADHD group (n = 52) were significantly higher than the control group (n = 52) (p < 0.01). There was a positive correlation between the higher scores of eveningness and total scores on resistance to sleep time (p < 0.09), respiratory problems during sleep and daytime sleepiness in the ADHD group. CSHQ total score was found to be a predictive factor for eveningness among children with ADHD (p < 0.01). These findings highlight possible reciprocal links between ADHD symptoms, sleep disturbances and chronotype in children aged 7–12 years, which might lead to individualized treatment options.     

Eveningness as a risk for behavioral problems in late adolescence

Circadian preference toward eveningness has been associated with increased risk for mental health problems both in early adolescence and in adulthood. However, in late adolescence, when circadian rhythm naturally shifts to later, its significance for mental health is not clear. Accordingly, we studied how circadian rhythm estimated both by self-reported chronotype and by actigraph-defined midpoint of sleep was associated with self-reported psychiatric problems based on Youth Self Report (YSR). The study builds on a community cohort born in 1998, Helsinki, Finland. At age 17 years (mean age = 16.9, SD = 0.1 years), 183 adolescents (65.6% of the invited) participated in the study. We used the shortened version of the Horne-Östberg morningness–eveningness Questionnaire to define the chronotype, and actigraphs to define the naturally occur circadian rhythm over a 4 to 17 days’ period (mean nights N = 8.3, SD = 1.8). The Achenbach software was used to obtain T-score values for YSR psychiatric problem scales. The analyses were adjusted for important covariates including gender, socioeconomic status, body mass index, pubertal maturation, mother’s licorice consumption during pregnancy, and actigraph-defined sleep duration and quality. Eveningness was associated with higher scores in rule-breaking behavior and conduct problems (as assessed either by midpoint of sleep or by self-reported chronotype, p-values <0.05), attention deficit/hyperactivity problems (by self-reported chronotype, p-values <0.05), with affective problems (by midpoint of sleep and by self-reported chronotype, p-values <0.05) and somatic complaints (by self-reported chronotype, p-values <0.05), as compared to circadian tendency toward morningness. Our results suggest that the association between eveningness and externalizing problem behavior, present in children and younger adolescents, is also present in late adolescence when circadian rhythms shift toward evening.     

Phase Angle of Entrainment in Morning‐ and Evening‐Types under Naturalistic Conditions

Differences in morningness‐eveningness among humans are commonly ascribed to circadian parameters, such as circadian period and responsivity to environmental time cues, as well as homeostatic sleep drive. Light is the primary synchronizer of the human biological clock, and if circadian differences exist between morning and evening types, they should have different phase angles of entrainment to the light/dark cycle; that is, morning and evening types should have different patterns of light exposure relative to endogenous circadian phase (ECP). When phase angle of entrainment is strictly defined as the relationship between a marker of ECP and the timing of light exposure, such differences have been demonstrated in the laboratory under controlled light/dark cycles and have recently been shown under conditions of spring and summer light exposure outside the laboratory, taking into account the variable intensity of light. Here, we report similar results from a large (n=66), diverse cohort of morning and evening types across the age span studied at all different times of the year. Differences between morning and evening types in light exposure relative to ECP, indicative of a difference in the phase angle of entrainment to the external light/dark cycle, were found. Specifically, evening types, compared to morning types, had a higher ratio of phase advancing to phase delaying by light. We interpret this as indicating a longer circadian period (τ) in evening types.     

Eveningness and poor sleep quality contribute to depressive residual symptoms and behavioral inhibition in patients with bipolar disorder

ABSTRACT

Eveningness and sleep disturbances are considered as markers of Bipolar Disorder (BD) and influence mood and emotional or behavioral states. This study investigates the associations between circadian markers and sleep quality on residual depressive symptoms and inhibition/activation dimensions during the euthymic phase. A sample of 89 euthymic adult individuals with BD was assessed for circadian preference and typology using the Composite Scale of Morningness (CSM) and the Circadian Type Inventory (CTI) and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The Montgomery and Asberg Depression Rating Scale (MADRS) and the Multidimensional Assessment of Thymic States (MAThyS) were used to measure residual depressive symptoms and the inhibition/activation dimensions. We examined any associations between these parameters using correlations and path analyses. We identified significant associations between eveningness and poorer sleep quality that correlated to higher depressive residual symptoms and a global inhibition. The use of path analyses led us to conclude that poor sleep quality mediated the relationship between eveningness and either residual mood symptoms or behavioral inhibition (motivation, sensory perception, interpersonal interaction, and cognition). These factors should be considered in the clinical evaluation of individuals with BD, with a specific attention during the euthymic phase, in order to achieve the best functional outcome possible.     

Changes in growth and sleep across school nights,weekends and a winter holiday period in two Australian schools

Studies suggest that there may be an association between sleep and growth; however, the relationship is not well understood. Changes in biology and external factors such as school schedule heavily impact the sleep of adolescents, during a critical phase for growth. This study assessed the changes in sleep across school days, weekends and school holidays, while also measuring height and weight changes, and self-reported alterations in food intake and physical activity. The impact of morningness–eveningness (M-E) on height change and weight gain was also investigated. In a sample of 63 adolescents (mean age = 13.13, SD = 0.33, 31 males) from two independent schools in South Australia, height and weight were measured weekly for 4 weeks prior to the school holidays and 4 weeks after the school holidays. Participants also completed a Morningness/Eveningness Scale and 7-day sleep, diet and physical activity diaries prior to, during and after the school holidays. Participants at one school had earlier wake times during the weekends than participants attending the other school, leading to a significantly shorter sleep duration on weekends for those participants. Regardless of school, sleep was significantly later and longer during the holidays (p < 0.001) and those with a stronger morning preference fell asleep (F_18,36 = 3.4, p = 0.001) and woke (F_18,44 = 2.0, p = 0.027) earlier than evening types. Growth rate was lower during the holiday weeks. For those attending the school with limited sleep in opportunities, growth after the holidays was lower for those with greater evening preference, whereas for those at the other school, growth was greater for those with greater evening preference. The increase in average weight from pre- to post-holidays was greater for those attending the school with limited opportunities to sleep longer. Participants reported greater food intake during the holidays compared to school days and greater physical activity levels on weekends compared to school days, and school days compared to holidays. Results suggest that time of day preference may impact growth, with evening types who cannot sleep in growing at a slower rate than evening types who can or morning types. This may be related to sleep restriction. Despite sleep being both later and longer during the school holidays, participants’ growth slowed during the holiday period. It is possible that this may be a reflection of other behavioural changes in the holidays (increased food intake and reduced physical activity), as sleep timing during the school period was related to growth.     

Clinical correlates of chronotypes in young persons with mental disorders

While important changes in circadian rhythms take place during adolescence and young adulthood, it is unclear how circadian profiles during this period relate to emerging mental disorders. This study aimed to: (i) characterise morningness–eveningness preference in young people with primary anxiety, depression, bipolar or psychotic disorders as compared to healthy controls, and (ii) to investigate associations between morningness–eveningness preference and the severity of psychiatric symptoms. Four hundred and ninety-six males and females aged between 12 and 30 years were divided into five groups according to primary diagnosis. The Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale were administered by a research psychologist and participants completed the Kessler Psychological Distress Scale and the Horne–Östberg Morningness–Eveningness Questionnaire (ME). ME scores were significantly lower (i.e. higher levels of “eveningness”) in all patient diagnosis subgroups compared to the control group. The psychosis group had higher ME scores than the depression and anxiety groups. Compared to the control group, the anxiety, depression and bipolar subgroups had a significantly higher proportion of “moderate evening” types, with a similar trend for the psychosis group. The proportion of “extreme evening” types was significantly higher in the anxiety and depression subgroups than in the control group. Lower ME scores correlated with worse psychological distress in males from the bipolar group. Lower ME scores correlated with higher depression severity in females with depression and in males with bipolar disorder. These results suggest that young persons with various mental disorders, especially those with affective disorders, present with a stronger “eveningness” preference and higher rates of evening chronotypes than healthy controls from the same age group. Later chronotypes were generally associated with worse psychological distress and symptoms severity. These associations were modulated by sex and primary diagnosis.     

Associations between chronotype,sleep disturbances and seasonality with fatigue and inflammatory bowel disease symptoms

Growing number of studies suggests link between circadian rhythms and inflammatory bowel diseases (IBD) manifestation. We hypothesize that: 1) IBD are associated with increased eveningness and sleep disturbances; 2) eveningness and sleep disturbances are related to more severe IBD symptoms. In total, 129 participants were enrolled to this study, divided into three groups: 34 Crohn’s disease (CD) patients, 38 ulcerative colitis (UC) patients and 57 healthy controls (HC) group. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Seasonal Pattern Assessment Questionnaire (SPAQ), Pittsburgh Sleep Quality Index, Inflammatory Bowel Disease Questionnaire (IBDQ) and Multidimensional Fatigue Inventory (MFI). Multiple regression models controlled for age and sex revealed that in CD group higher eveningness measured with CSM was associated with higher general fatigue, physical fatigue, mental fatigue and reduced motivation measured by MFI. Lower CSM morning affect is associated with greater general fatigue, physical fatigue and more reduced activity. Greater seasonality scores are associated with increased physical fatigue and more reduced activity and motivation. Lower sleep quality measured with PSQI is associated with higher physical fatigue and more reduced activity. Correlational analysis revealed that higher seasonality and lower sleep quality are associated with increased systemic and bowel symptoms and decreased emotional and social functions measured with IBDQ. In UC group, eveningness is associated with greater general fatigue, physical fatigue and more reduced activity. Higher CSM morning affect is associated with decreased general fatigue, physical fatigue and less reduced activity. Higher CSM circadian preference scores are associated with decreased general and physical fatigue, and less reduced activity. Increased seasonality is associated with more physical fatigue. Lower sleep quality is associated with greater general and physical fatigue. To our best knowledge this is the first study evaluating associations between chronotype and sleep disturbances with IBD symptoms. We have found that chronotype preferences, whose role in IBD has been until now overlooked, may be one of the important factors contributing to fatigue in this clinical group.     

Morningness–eveningness questionnaire score and metabolic parameters in patients with type 2 diabetes mellitus

“Morningness” and “Eveningness” represent lifestyle patterns including sleep–wake patterns. Although previous studies described a relationship between the morningness–eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness–eveningness questionnaire (MEQ). The relationships between morningness–eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n?=?117), neither type (n?=?424) and evening type (n?=?184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.     

Relation of chronotype to sleep complaints in the general Finnish population

Individuals show variation in their preference for the daily timing of activities. In this study the authors analyzed whether chronotypes associate with sleep duration and sleep-related complaints. The authors used the National FINRISK Study 2007 Survey data on 3696 women and 3162 men, representative of the Finnish population aged 25 yrs and older, for the assessment of chronotype and self-reported sleep. Evening types experienced insomnia symptoms, had nightmares, and had used recently hypnotics significantly more often than other chronotypes among both men and women. In a multinominal logistic regression model predicting insufficient sleep, the association of eveningness with insufficient sleep was not abolished after adjustment for sex, age, and sleep duration. The prevalence of short sleepers was significantly higher in evening types among men than among women, whereas that of long sleepers was significantly higher in evening types among both men and women, as compared with the other chronotypes. These results indicate that eveningness predisposes individuals to a range of sleep complaints.     

Morningness–eveningness interferes with perceived health,physical activity,diet and stress levels in working women: A cross-sectional study

Sleep and health are closely interrelated and sleep quality is a well-known contributor to perceived health. However, effects of sleep-timing preference i.e. morningness–eveningness on health has yet to be revealed. In this study, we explored the relationship between morningness–eveningness and perceived health in a sample of female working professionals (N?=?202). Sleep-timing preference was measured using the Composite Scale of Morningness. Perceived health was characterized by Center for Epidemiologic Studies Depression Scale, WHO Well-Being Scale-5 and Patient Health Questionnaire-15 scores. We also investigated possible mechanisms, including stress and health-impairing behaviours. In accordance with previous data, we found more depressive mood, lower well-being and poorer perceived health among evening types. To assess health-impairing behaviours we collected data on smoking habits, alcohol consumption, physical activity and diet. Among the possible mechanism variables, greater stress, less frequent physical activity and less healthy diet were associated with eveningness. Furthermore, stress diminished the strength of the association between morningness–eveningness and depressed mood. Physical activity attenuated the strength of the association between morningness–eveningness and well-being. No effects of alcohol consumption could be identified. Our data show that evening preference behaves as a health risk in terms of associating with poor perceived health. Our findings also suggest that this effect might be mediated by health behaviours and stress.     

Association between morningness-eveningness and behavioral/emotional problems among adolescents

Adolescent eveningness is associated with age, parental monitoring, daytime sleepiness, sleep problems, moodiness, and the use of coffee. This study investigated the association between adolescent morningness-eveningness and psychopathology, substance use, and suicidality in 1332 students ages 12 to 13. Each student-participant completed the Chinese version of the Child Morningness/Eveningness Scale (CMES), the Pubertal Development Scale, and a questionnaire about their sleep schedule, trouble sleeping, habitual substance use, and suicidality. Their mothers completed the Child Behavioral Checklist and Chinese Health Questionnaire. The morning (n = 412), intermediate (n = 740), and evening (n = 180) groups were operationally defined by the CMES t scores. The mixed model was used for data analysis. The evening group had shorter weekday sleep time, longer weekend sleep time, more daytime napping, and greater sleep compensation on weekends and was more likely than the other 2 groups to have behavioral/emotional problems, suicidality, and habitual substance use. Internalizing and externalizing problems partially explained the association between eveningness, substance use, and suicidality. The findings suggest that eveningness may be an indicator for adolescents with behavioral/emotional problems and risky behaviors and suggest an investigation for possible intervention.     

Timing and consolidation of human sleep, wakefulness, and performance by a symphony of oscillators

Daily rhythms in sleep and waking performance are generated by the interplay of multiple external and internal oscillators. These include the light-dark and social cycles, a circadian hypothalamic oscillator oscillating virtually independently of behavior, and a homeostatic oscillator driven primarily by sleep-wake behavior. Both internal oscillators contribute to variation in many aspects of sleep and wakefulness (e.g., sleep timing and duration, REM sleep, non-REM sleep, REM density, sleep spindles, slow-wave sleep, electroencephalographic oscillations during wakefulness and sleep, and performance parameters, including attention and memory). The relative contribution of the oscillators varies greatly between these variables. Sleep and performance cannot be predicted by either oscillator independently but critically depend on their phase relationship and amplitude. The homeostatic oscillator feeds back onto the central pacemaker or its outputs. Thus, the amplitude of observed circadian variation in sleep and performance depends on how long we have been asleep or awake. During entrainment to external 24-h cycles, the opposing interplay between circadian and homeostatic changes in sleep propensity consolidates sleep and wakefulness. Some physiological correlates and mediators of both the circadian process (e.g., melatonin and hypocretin rhythms) and the homeostat (e.g., EEG, slow-wave activity, and adenosine release) have been established, offering targets for the development of countermeasures for circadian sleep and performance disorders. Interindividual differences in sleep timing, duration, and morning or evening preference are associated with changes of circadian or sleep homeostatic processes or both. Molecular genetic correlates, including polymorphisms in clock genes, of some of these interindividual differences are emerging.     

Age-related changes in the circadian and homeostatic regulation of human sleep

The reduction of electroencephalographic (EEG) slow-wave activity (SWA) (EEG power density between 0.75-4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non-rapid eye movement (NREM) sleep consolidation reflects an age-related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age-related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency-the latter was phase-advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age-related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age-related decrements in sleep and daytime alertness levels.     

Age‐related Changes in the Circadian and Homeostatic Regulation of Human Sleep

The reduction of electroencephalographic (EEG) slow‐wave activity (SWA) (EEG power density between 0.75–4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non‐rapid eye movement (NREM) sleep consolidation reflects an age‐related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age‐related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency—the latter was phase‐advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age‐related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age‐related decrements in sleep and daytime alertness levels.     

Association study of a variable-number tandem repeat polymorphism in the clock gene PERIOD3 and chronotype in Norwegian university students

Circadian rhythms are endogenously generated cycles involving physiological parameters, such as core body temperature, hormone levels, blood pressure, sleep, and metabolism, with a period length of around 24?h. The circadian clock in mammals is regulated by a set of clock genes that are functionally linked together, and polymorphisms in clock genes could be associated with differences in circadian rhythms. A variable-number tandem repeat (VNTR) in the human clock gene PERIOD3 (PER3) has been suggested to correlate with a morning (lark) versus evening (owl) chronotype as well as with the circadian rhythm sleep disorder ?delayed sleep phase disorder? (DSPD). The authors examined 432 healthy Norwegian university students in search of further support for an association between the PER3 polymorphism and diurnal preference. The Horne-?stberg Morningness-Eveningness Questionnaire (MEQ) and Preferences Scale (PS) were used to evaluate subjective chronotype. DNA samples were genotyped with respect to the 4-repeat and 5-repeat alleles of the VNTR PER3 polymorphism, and the genotype distribution was 192 (4-4), 191 (4-5), and 49 (5-5). The authors estimated that the power to detect an association of the 4-allele with preference for morningness or eveningness was 75%. The authors found no association between the PER3 clock gene and chronotype, indicating that the proposed role of PER3 needs further clarification.     

Human diurnal preference and circadian rhythmicity are not associated with the CLOCK 3111C/T gene polymorphism

Genetic association studies of the CLOCK 3111C/T polymorphism and diurnal preference have yielded conflicting results since the first report that the 3111C allele was associated with eveningness. The goal of the present study was to investigate the association of this polymorphism with diurnal preference and circadian physiology in a group of 179 individuals, by comparing the frequency of the 3111C allele to diurnal preference, habitual sleep timing, circadian phase markers, and circadian period. We did not find a significant association between this allele and morningness/eveningness or any circadian marker.