A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring

Mounting epidemiologic and scientific evidence indicates that many psychiatric disorders originate from a complex interplay between genetics and early life experiences, particularly in the womb. Despite decades of research, our understanding of the precise prenatal and perinatal experiences that increase susceptibility to neurodevelopmental disorders remains incomplete. Sleep apnea (SA) is increasingly common during pregnancy and is characterized by recurrent partial or complete cessations in breathing during sleep. SA causes pathological drops in blood oxygen levels (intermittent hypoxia, IH), often hundreds of times each night. Although SA is known to cause adverse pregnancy and neonatal outcomes, the long-term consequences of maternal SA during pregnancy on brain-based behavioral outcomes and associated neuronal functioning in the offspring remain unknown. We developed a rat model of maternal SA during pregnancy by exposing dams to IH, a hallmark feature of SA, during gestational days 10 to 21 and investigated the consequences on the offspring’s forebrain synaptic structure, synaptic function, and behavioral phenotypes across multiples stages of development. Our findings represent a rare example of prenatal factors causing sexually dimorphic behavioral phenotypes associated with excessive (rather than reduced) synapse numbers and implicate hyperactivity of the mammalian target of rapamycin (mTOR) pathway in contributing to the behavioral aberrations. These findings have implications for neuropsychiatric disorders typified by superfluous synapse maintenance that are believed to result, at least in part, from largely unknown insults to the maternal environment.

Correlative data in humans has hinted at an association between maternal sleep apnea during pregnancy and altered neuronal function in offspring. This study shows that in a rat model of sleep apnea, maternal gestational intermittent hypoxia leads to sex-specific changes in neuronal structure and function in offspring, accompanied by impaired behavioral phenotypes.     

The features of sleep homeostasis in pregnant rats

To investigate the effects of short-term sleep deprivation on the sleep pattern during pregnancy, cortical and hippocampal EEG and locomotor activity were recorded within 24-hours in a "disk-over-water" paradigm in 18 Wistar rats. Rats were adapted to experimental situation and were able to move across the rotating disk without falling in water. Then a polysomnogram was recorded for 3 sequential days in the control group 1 (n = 12) without disk rotation. On the next day non-pregnant rats (experimental group 1, n = 6) were subjected to the sleep deprivation procedure with a pre-set program of disk rotation from 11:00 to 14:00 during 3 sequential days. Other 6 rats (experimental group 2) were subjected to sleep deprivation on the 5-7th day of pregnancy. EEG and locomotor activity were also constantly recorded during the sleep deprivation procedure. In control group 2 (n = 6, without sleep deprivation), a polysomnogram was recorded on the 5-7th day of pregnancy. As compared to non-pregnant rats, sleep intensity of pregnant rats increased during the first hours after the deprivation, and a considerable rebound of REM sleep took place. Sleep pattern during the off-light 12 hours remained unchanged. The results suggest that homeostatic compensation of sleep deprivation effects in rats on the first week of pregnancy is more efficient than in control non-pregnant animals.     

Accuracy of Self-Reported Sleep Position in Late Pregnancy

Background

There is emerging research to suggest that supine maternal sleep position in late pregnancy may adversely affect fetal wellbeing. However, these studies have all been based on maternal report of sleeping position. Before recommendations to change sleep position can be made it is important to determine the validity of these studies by investigating how accurate pregnant women are in reporting their sleep position. If avoiding the supine sleeping position reduces risk of poor pregnancy outcome, it is also important to know how well women can comply with the instruction to avoid this position and sleep on their left.

Method

Thirty women in late pregnancy participated in a three-night observational study and were asked to report their sleeping position. This was compared to sleep position as recorded by a night capable video recording. The participants were instructed to settle to sleep on their left side and if they woke overnight to settle back to sleep on their left.

Results

There was a moderate correlation between reported and video-determined left-side sleep time (r = 0.48), mean difference = 3 min (SD = 3.5 h). Participants spent an average of 59.60% (SD = 16.73%) of time in bed on their left side (ICC across multiple nights = 0.67). Those who included left side among their typical sleep positions reported significantly longer sleep during the study (p<0.01).

Conclusions

On average participant reports of sleep position were relatively accurate but there were large individual differences in reporting accuracy and in objectively-determined time on left side. Night-to-night consistency was substantial. For those who do not ordinarily sleep on that side, asking participants to sleep on their left may result in reduced sleep duration. This is an important consideration during a sleep-critical time such as late pregnancy.     

Changes in sleep patterns during prolonged stays in Antarctica

Various countries have permanent research bases in Antarctica that are manned year-round by a few members of an expedition team, facing extremes of temperature with the associated hardships. Acclimatisation to such an environment is associated with pyschophysiological changes along with alterations in sleep patterns. The present study was undertaken to explore the changes in sleep patterns of six members of the Indian expedition team during their winter stay at Maitri, the permanent research station of India in Antarctica. The mean (+/- SEM) age, height and weight of the subjects were 35.7 +/- 2.32 years, 168.3 +/- 2.37 cm and 71.0 +/- 1.88 kg, respectively. Polysomnographic sleep recordings were obtained as baseline data in November 2004 in Delhi (altitude 260 m, latitude 29 degrees N, longitude 77 degrees E); data on the same parameters were collected at Maitri, Antarctica (altitude 120 m, latitude 70 degrees 45' 39' S, longitude 11 degrees 44' 49' E) from January to December 2005. A one-way analysis of variance with repeated measures showed a significant variation with time (month effect) in most of the sleep parameters recorded. Total sleep time decreased from Delhi baseline values in all months, sleep efficiency decreased significantly during winter months, duration of waking period after sleep onset increased significantly in winter, sleep latency increased immediately after exposure in January, stages 3 and 4 (slow wave sleep) reduced during dark winter months, whereas stages 1 and 2 and rapid eye movement sleep increased during dark winter months. This study observed a prevailing general trend of sleep disturbances amongst overwintering members in a modern Antarctic station.     

Eveningness associates with smoking and sleep problems among pregnant women

Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness–eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.     

Periodic limb movements in sleep during pregnancy: a common but benign disorder?

Pregnant women have a two- to threefold increased prevalence of restless legs syndrome (RLS) compared to the general population, and the majority of RLS patients also experience periodic limb movements in sleep (PLMS). PLMS have been associated with sleep disturbance as well as autonomic heart rate and blood pressure responses; however, the prevalence, cause and significance of PLMS during pregnancy remain unknown. This study evaluated the presence of PLMS in late pregnancy and its relationship to hypertensive disorders of pregnancy. Ninety-one women in the third trimester of pregnancy underwent overnight polysomnography. An RLS questionnaire and the Multivariate Apnea Risk Index were administered and venous blood was sampled within 2 weeks of the sleep study. After exclusions due to obstructive sleep apnoea and signal loss, PLMS data were available for 73 women, 36 hypertensive women and 37 BMI- and gestation-matched controls. PLMS were found to be very common during pregnancy; 45% of women had a PLMS index > 5 and 25% had a PLMS index > 15. The number of PLMS per hour did not differ by hypertensive status. Sleep quality was mostly unaffected by PLMS, as was change in blood pressure overnight. While RLS was reported by 18.3% of the sample, this did not reliably predict the presence of PLMS. Despite iron deficiency being common in this population, it was not associated with PLMS. This novel study investigating the frequency and impact of PLMS during pregnancy revealed that PLMS are very common in the third trimester; however, this disorder appears to be benign in terms of objective sleep quality and relationship with pregnancy-related hypertension.

     

Day-to-day alteration of 24-hour sleep pattern immediately before and after giving birth

Sleep and Biological Rhythms - The current literature suggests that nighttime sleep is compromised during late pregnancy and early postpartum periods, but little is known about the 24-hour sleep...     

Intimate Partner Violence Is Associated with Stress-Related Sleep Disturbance and Poor Sleep Quality during Early Pregnancy

Objectives

To examine the associations of Intimate partner violence (IPV) with stress-related sleep disturbance (measured using the Ford Insomnia Response to Stress Test [FIRST]) and poor sleep quality (measured using the Pittsburgh Sleep Quality Index [PSQI]) during early pregnancy.

Methods

This cross-sectional study included 634 pregnant Peruvian women. In-person interviews were conducted in early pregnancy to collect information regarding IPV history, and sleep traits. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CIs) were calculated using logistic regression procedures.

Results

Lifetime IPV was associated with a 1.54-fold increased odds of stress-related sleep disturbance (95% CI: 1.08–2.17) and a 1.93-fold increased odds of poor sleep quality (95% CI: 1.33–2.81). Compared with women experiencing no IPV during lifetime, the aOR (95% CI) for stress-related sleep disturbance associated with each type of IPV were: physical abuse only 1.24 (95% CI: 0.84–1.83), sexual abuse only 3.44 (95%CI: 1.07–11.05), and physical and sexual abuse 2.51 (95% CI: 1.27–4.96). The corresponding aORs (95% CI) for poor sleep quality were: 1.72 (95% CI: 1.13–2.61), 2.82 (95% CI: 0.99–8.03), and 2.50 (95% CI: 1.30–4.81), respectively. Women reporting any IPV in the year prior to pregnancy had increased odds of stress-related sleep disturbance (aOR = 2.07; 95% CI: 1.17–3.67) and poor sleep quality (aOR = 2.27; 95% CI: 1.30–3.97) during pregnancy.

Conclusion

Lifetime and prevalent IPV exposures are associated with stress-related sleep disturbance and poor sleep quality during pregnancy. Our findings suggest that sleep disturbances may be important mechanisms that underlie the lasting adverse effects of IPV on maternal and perinatal health.     

A comparison of methods to determine center of mass during pregnancy

Balance changes during pregnancy likely occur because of mass gains and mass distribution changes. However, to date there is no way of tracking balance through center of mass motion because no method is available to identify of the body center of mass throughout pregnancy. We compared methods for determining segment masses and torso center of mass location. The availability of a method for tracking these changes during pregnancy will make determining balance changes through center of mass motion an option for future pregnancy balance research. Thirty pregnant women from eight weeks gestation until birth were recruited for monthly anthropometric measurements, motion capture analysis of body segment locations, and force plate analysis of center of pressure during quiet standing and supine laying. From these measurements, we were able to compare regression, volume measurement, and weighted sum methods to calculate body center of mass throughout pregnancy. We found that mass changes around the trunk were most prevalent as expected, but mass changes throughout the body (especially the thighs) were also seen. Our findings also suggest that a series of anthropometric measurements first suggested by Pavol et al. (2002), in combination with quiet standing on a force plate, can be used to identify the needed components (segment masses and torso center of mass location in three dimensions) to calculate body center of mass changes during pregnancy. The results of this study will make tracking of center of mass motion a possibility for future pregnancy balance research.     

Sleep, learning, and birdsong

Neuroethological research combines approaches derived from animal behavior and neurobiology to examine the neuronal mechanisms of behavior, often in the context of laboratory experiments on species chosen for particular adaptations. Typically, these species are not traditional laboratory animals yet they contribute greatly to a broad, evolutionarily diverse view of nervous system function. The surprising role of sleep in the vocal learning process of songbirds is one such example, described here. Juvenile zebra finches show sleep-dependent daytime fluctuations in their patterns of singing starting after their first exposure to tutor songs. Nighttime bursting activity in the vocal control song system also changes after the onset of tutoring, with the neuronal changes preceding the changes in objective behavior (daytime singing). After tutoring, the nighttime bursting increases and exhibits structure that depends on the particular tutor song, and the nighttime expression of these changes requires normal auditory feedback during daytime singing. These observations shed light on the information carried in neuronal activity during sleep and on the adaptive plastic mechanisms engaged during sleep. They suggest a new hypothesis of sensorimotor learning, whereby sensory memories act indirectly on sensorimotor feedback by modifying networks through plastic changes at night. Sleep may also contribute to adult song maintenance, with nighttime neuronal replay conveying information about songs produced during the day and possibly mediating daily changes in the structure of premotor bursts. Collectively, these insights contribute a comparative perspective to theories of sleep and memory, which also help to inform a developing understanding of how humans acquire and retain memories.     

Ventilation during early and late rapid-eye-movement sleep in normal humans.

Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters.     

Tryptophan feeding adversely influences pregnancy

Additional tryptophan during pregnancy reduces embryo and neonate survival in the golden hamster, $\text{Mesocricetus auratus}$.Relatively small doses of exogenous serotonin have been reported to cause abortions in several vertebrate species (1, 2, 3, 4, 5). Smaller doses reduce litter sizes, increase still births and neonate abnormalities, and otherwise influence pregnancy adversely. These effects are produced by serotonin throughout pregnancy, beginning at implantation (6).The availability of tryptophan is probably the most important rate limiting factor in serotonin synthesis (7). Inasmuch as tryptophan is an essential amino acid and is not synthesized by the body, the diet is the sole source; studies have shown that increases (8) or decreases (9) in dietary tryptophan lead to concomitant changes in serotonin content. Because tryptophan is employed in humans to promote sleep (10, 11, 12) and to decrease appetite (13) we felt it might be important to test whether increased amounts of diet tryptophan can adversely influence pregnancy.     

Can Insomnia in Pregnancy Predict Postpartum Depression? A Longitudinal,Population-Based Study

Background

Insomnia and depression are strongly interrelated. This study aimed to describe changes in sleep across childbirth, and to evaluate whether insomnia in pregnancy is a predictor of postpartum depression.

Methods

A longitudinal, population-based study was conducted among perinatal women giving birth at Akershus University Hospital, Norway. Women received questionnaires in weeks 17 and 32 of pregnancy and eight weeks postpartum. This paper presents data from 2,088 of 4,662 women with complete data for insomnia and depression in week 32 of pregnancy and eight weeks postpartum. Sleep times, wake-up times and average sleep durations were self-reported. The Bergen Insomnia Scale (BIS) was used to measure insomnia. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure depressive symptoms.

Results

After delivery, sleep duration was reduced by 49 minutes (to 6.5 hours), and mean sleep efficiency was reduced from 84% to 75%. However, self-reported insomnia scores (BIS) improved from 17.2 to 15.4, and the reported prevalence of insomnia decreased from 61.6% to 53.8%. High EPDS scores and anxiety in pregnancy, fear of delivery, previous depression, primiparity, and higher educational level were risk factors for both postpartum insomnia and depression. Insomnia did not predict postpartum depression in women with no prior history of depression, whereas women who recovered from depression had residual insomnia.

Limitations

Depression and insomnia were not verified by clinical interviews. Women with depressive symptoms were less likely to remain in the study.

Conclusions

Although women slept fewer hours at night after delivery compared to during late pregnancy, and reported more nights with nighttime awakenings, their self-reported insomnia scores improved, and the prevalence of insomnia according to the DSM-IV criteria decreased. Insomnia in pregnancy may be a marker for postpartum recurrence of depression among women with previous depression.     

Cocaine effects on neonatal heart rate dynamics: preliminary findings and methodological problems.

Cocaine use by pregnant women has been reported to cause fetal and neonatal morbidity and mortality. We hypothesized that human neonates exposed to cocaine via maternal use during pregnancy might manifest changes in beat-to-beat heart rate variability, similar to those described in experimental animals. In this preliminary report, we present findings from the first systematic analysis of heart rate dynamics in a small group of (n = 5) neonates exposed in utero to cocaine compared to gestationally age matched controls (n = 6) without known drug exposure. Overall heart rate spectral power during ten minute periods of quiescent sleep was significantly reduced (p < 0.01) in the cocaine-exposed group, reminiscent of the changes recently reported in an animal model. In two other cocaine-exposed newborns, a quiescent sleep period could not be found. We discuss the special methodological problems associated with collection and interpretation of such data.     

Ecstasy and sleep disturbance: Progress towards elucidating a role for the circadian system

MDMA (ecstasy) is an illicit drug which has pharmacological actions on the serotonin system, leading to a number of physiological and behavioral changes. Research conducted in both animals and humans has focused on how ecstasy use affects systems or functions in which serotonin has a regulatory role including mood, sleep and circadian rhythms. In this paper we review the evidence with respect to changes in sleep and circadian rhythms following ecstasy use. Studies of the subjective measurement of sleep have suggested that there are changes in sleep quality and duration following ecstasy use, while research utilizing objective measures including polysomnog-raphy has highlighted changes in sleep architecture following ecstasy use. Collectively these findings suggest that there are consequences associated with ecstasy use, and the implications of these findings for ecstasy users will be examined. Finally, preliminary evidence from the animal literature implicating ecstasy as having specific effects on the circadian system will be reviewed. A discussion of the limitations of the current evidence for such a claim is presented, and possible directions for future research are explored.

     

Effects of selective sleep deprivation on ventilation during recovery sleep in normal humans.

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.     

Emotional sensitivity for motherhood: Late pregnancy is associated with enhanced accuracy to encode emotional faces

Previous research suggests that female sex hormones can increase the sensitivity of women's emotion processing systems. The largest rises in sex hormone levels in a woman's life are from early to late pregnancy. The current study, therefore, investigated whether changes in emotion processing are seen across pregnancy. Hypervigilant emotion processing has been implicated in the aetiology of anxiety. Therefore enhanced emotion processing across pregnancy has implications for women's vulnerability to anxiety. Ability to encode facial expressions of emotion was assessed in 101 women during early pregnancy and again in 76 of these women during late pregnancy. Symptoms of anxiety were measured using a clinical interview (The CIS-R). Consistent with previous research, the presence of anxiety symptoms was associated with greater accuracy to encode faces signalling threat (fearful and angry faces). We found that women had higher accuracy scores to encode emotional expressions signalling threat or harm (fearful, angry and disgusted faces) but also a more general negative emotion (sadness) during late, compared with early, pregnancy. Enhanced ability to encode emotional faces during late pregnancy may be an evolutionary adaption to prepare women for the protective and nurturing demands of motherhood by increasing their general emotional sensitivity and their vigilance towards emotional signals of threat, aggression and contagion. However, the results also suggest that, during late pregnancy, women's emotion processing style is similar to that seen in anxiety. The results have implications for our understanding of normal pregnant women's processing of emotional cues and their vulnerability to symptoms of anxiety.     

Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: Effects of maternal body mass index

BackgroundThe maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated.MethodsThis study examined serum proinflammatory markers interleukin(IL)-6, IL-8, tumor necrosis factor (TNF)-α, IL-1β, and C-reactive protein (CRP) during each trimester of pregnancy and 4–6 weeks postpartum among 57 women.ResultsOverall, IL-6 showed an increasing trend across pregnancy and significant increase at postpartum. Similarly, TNF-α increased significantly across gestation, with a further increase at postpartum. Both IL-8 and IL-1β showed a U-shaped curve, decreasing from early to later pregnancy, and increasing at postpartum. Finally, serum CRP decreased significantly across pregnancy, with further decreases at postpartum. Maternal obesity predicted higher IL-6 at each study visit. Obese women showed a trend toward elevated serum CRP during pregnancy, and significantly higher levels at postpartum.DiscussionThe course of pregnancy and postpartum is characterized by significant changes in serum proinflammatory mediators. Obese women show elevations in serum proinflammatory markers relative to normal weight women during pregnancy and postpartum. Further research is needed to determine the extent to which obesity-induced inflammation affects maternal and fetal health.     

Longitudinal Study of Mothers’ Sleep-Wake Behaviors and Circadian Time Patterns from Late Pregnancy to Postpartum – Monitoring of Wrist Actigraphy and Sleep Logs

This longitudinal study investigated sleep-wake behavior patterns during and after pregnancy, using an actimeter worn on the non-dominant wrist and a sleep log. Records were obtained from ten mothers, from the 34th week of gestation until the 15th week postpartum. Ten non-pregnant women were used as a control group, data being collected from them for 2 weeks. The sleep-wake behavior after delivery, obtained from wrist actigraphy, was greater in the postpartum period. Total sleep time, sleep efficiency, and circadian amplitude decreased in the weeks immediately following parturition, but wake after sleep onset increased. Subsequently, all the sleep and circadian variables improved slightly, but they had not returned to the levels of the non-pregnant control group even by the 15th postpartum week. The length of daytime naps increased, in order to make up for nocturnal sleep deprivation when the number of awakenings during nighttime had increased. There were significant positive correlations between total sleep time, sleep efficiency, wake after sleep onset, and the length of daytime naps, but the numbers of awakenings at night and daytime naps did not show this correlation. The total sleep time indicated by sleep logs tended to be greater than that indicated by actigraphy, but wake after sleep onset tended to be underestimated by the sleep logs. The implications of these results are discussed.     

Growth and development of children with a special focus on sleep

The first two decades of life are characterised complex biological processes involving growth and maturation as well as differentiation. The Central Nervous System (CNS) where among others internal and external stimuli are integrated and responses of the body are prepared starts to evolve quite early during ontogenesis. One of the complex behaviours, which are regulated by the brain, is the sleep-wake cycle.The discussion of age-related changes in sleep comprises changes at the physiological level (e.g. changes in the frequency and amplitude of EEG signal, as well as development and distribution of sleep stages), changes in the corresponding behaviour (e.g. changes in the absolute amount of sleep and its distribution in 24 h perspective), and finally the subjective perception of sleep and sleep as a measure of well-being.Studies on the impact of a specific factor on sleep during childhood and adolescence have to consider chronological and biological age as well as sex as relevant biological parameters. Even when these factors are controlled for large interindividual differences persist, that is why prospective instead of cross-sectional approaches should be used whenever possible. Furthermore, it has to be distinguished between sleep assessed at the level of brain functioning (i.e. by polysomnography), which gives information on effects at the physiological level and at the level of self-assessment, which focuses on behaviour. Both, sleep at the subjective as well as at the objective level, can to a considerable degree be affected by life style factors, which hence have to be considered as potential confounders.