A Novel Disease Condition Presenting with Insomnia and Hypersomnia Asynchronization Part 1


More than half of the preschoolers/students in Japan have recently complained of daytime sleepiness, while approximately one quarter of junior and senior high school students reportedly suffer from insomnia. These children might suffer from behavioral-induced insufficient sleep syndrome due to inadequate sleep hygiene, and conventional therapeutic approaches often fail. The present study addressed whether asynchronization, a novel clinical notion, could be responsible for the pathophysiology of these sleep disturbances and could provide a better understanding for successful interventions. This clinical concept was designed with special reference to the basic concept of singularity. The essence of asynchronization comprises disturbances in various aspects (e.g., cycle, amplitude, phase, and interrelationship) of biological rhythms that normally exhibit circadian oscillation. These disturbances presumably involve decreased activity of melatonergic and serotonergic systems. The major triggers for asynchronization are hypothesized to be a combination of light exposure during the night, which decreases melatonin secretion, as well as lack of light exposure in the morning, which decreases activity in the serotonergic system. Prevention of asynchronization must include acquisition of morning light and avoidance of nocturnal light. Possible potential therapeutic approaches for asynchronization involve conventional and alternative therapies. We should know more about the property of the biological clock.

Keywords: desynchronization; melatonin; serotonin; sleep; circadian rhythm; singularity


Circadian rhythms are generated in the suprachiasmatic nucleus (SCN). SCN development takes place throughout the course of gestation, remains immature for some time after birth, and is suggested to be vulnerable to maternal influences [1]. Studies have shown that the earlier mothers fell into nocturnal sleep during late pregnancy, the longer the babies slept during the night at one month of age [2]. The same report described that onset time for the longest nocturnal sleep of mothers during late pregnancy was similar to the babies at one month of age, suggesting that synchronization of sleep rhythm begins during late pregnancy. Because circadian rhythm disturbances in the young can impact SCN function during the lifespan, therapeutic strategies are much needed. Nevertheless, very little is understood regarding pathophysiology of circadian rhythm disruption, which makes it difficult to determine the appropriate clinical approach for these patients.

This review article introduces the recent phenomenon of a nocturnal lifestyle among youth in Japan, and the association between nocturnal lifestyle and behavior. In addition, the presumed involvements of neurological systems such as the biological clock, melatonergic system and serotonergic system in youth that prefer a nocturnal lifestyle are reviewed. Finally, a new clinical entity – asynchronization [3, 4] – has been proposed, in an attempt to elucidate the pathophysiology of circadian disruptions and to provide novel, clinical therapeutic approaches. This clinical concept has been termed with special reference to the basic concept of singularity. Circadian singularity behavior was discovered in 1970, according to observation that specific, dim, blue-light, pulse stimulus, with a unique stimulus time and duration, resulted in disturbed circadian rhythm in Drosophila [5].

Insomnia and Hypersomnia Among Japan Youth

Recent Statistics of Bedtime and Sleep Duration

The percentage of 1-year-old children who go to bed later than 22:00 has increased from 25.7% in 1980 to 54.4% in 2000. Similar statistics have also been reported for the rate of 3-year-old children who go to bed later than 22:00: 21.7% in 1980 [6], 43.8% in 1999 [7], 49.8% in 1999-2000 [8], 52.0% in 2000 [6], and 51.1% in 2004 [9].

The rate of fourth-grade students at elementary schools in Tokyo going to bed later than 0:00 has also increased from 0% in 1979 to 2% in 2002 [10]. The mean bedtime in 2004 for elementary school students in the fifth and sixth grade was 22:03, junior high school students was 23:18, and senior high school students was 0:06 [11]. An additional study from 2005 reported the mean bedtime for students in the fifth grade was 22:10, students in the second grade of junior high school was 23:26, and students in the second grade of senior high school had a mean bedtime of 23:50 [12]. Tagaya et al. reported an average bedtime of 0:03 from senior high school students in 2000 [13].

In 3-year-old children, the bedtime delay has resulted in a reduction of total daily sleep [8]. Indeed, in accordance with a recent development in later bedtimes, sleep duration of Japanese children has also reduced. Shimada et al [14] examined studies of sleep duration of infants, and concluded that sleep duration in the early 1990s decreased from 12.9 hours in 1985 [15] to 10.9 hours. The nocturnal sleep duration of children aged 3-6 years in 2000 (10.10 hours for children attending kindergarten, 9.35 hours for children attending nursery school, and 9.95 hours for children attending neither kindergarten nor nursery school) was reported to be 9-15 minutes less than in 1995 [16]. Among 21273 children aged 0-36 months from 12 different countries (United States, United Kingdom, Australia, New Zealand, Canada, Hong Kong, Korea, Taiwan, Thailand, Indonesia, Japan, China), Japanese children exhibited the shortest sleep duration (nap + nocturnal sleep duration) of 11.6 hours, while those in New Zealand revealed the longest duration of 13.3 hours [17].

Between 1965 and 2000, the sleep duration of elementary school, as well as junior and senior high school students, in Japan decreased on average by 1.1-1.6 minutes per year [18]. More specifically, mean nocturnal sleep duration in 2004 was 8.77 hours for elementary school students in fifth and sixth grade, 7.42 hours for junior high school students, and 6.55 hours for senior high school students [11]. Similarly, in 2005, mean nocturnal sleep duration was 8.40 hours for fifth-grade elementary school students, 7.23 hours for second-grade junior high school students, and 6.51 hours for second-grade senior high school students [12]. Tagaya et al. reported average sleep duration of senior high school students in 2000 to be 6.30 hours [13].

Complaints of Young People with Nocturnal Lifestyle

In 1979, 8.1% of children attending day nursery schools in Japan were reported to frequently yawn in the morning, and 10.5% were easily tired. By 2000, these numbers had increased remarkably to 53.2% and 76.6%, respectively [19]. Accordingly, approximately 80% of kindergarten and nursery school teachers reported that many children were sleep-deprived [20].

In 2004 in Tokyo, 50% of fifth- and sixth-grade elementary school boys, 60% of fifth-and sixth-grade elementary school girls, 70% of junior high school boys, and 80% of junior high school girls reportedly complained of sleepiness during the third and fourth lesson periods (from approximately 10:00 to 12:00) [21]. In contrast to the early morning (around 4:00) and afternoon (around 14:00) periods, late morning is the period when humans generally tend to be most alert and active [22].

In addition, 47.3%, 60.8%, and 68.3% of fifth-grade elementary school students, second-grade junior high school students, and second-grade senior high school students reportedly experienced sleep deficiency, respectively [12]. The reasons given for sleep deficiency indicated by these students are shown in Table 1.

A nationwide study to ascertain the prevalence of insomnia, the symptoms, and associated factors among students in junior and senior high schools in Japan revealed a prevalence of difficulty in initiating sleep (14.8%), difficulty maintaining sleep (11.3%), and early morning awakening (5.5%) [23]. The prevalence of insomnia, defined as the presence of one or more of these three symptoms, was 23.5%.

Table 1. Causes of sleep deficiency [12].

Elementary school students

Junior high school students

Senior high school students


Difficulties falling asleep (43.8%)

TV and video (44.5%)

Cellular phone use (42.4%)


TV and video (39.3%)

Homework (32.2%)

TV and video (38.8%)


Homework (26.3%)

Difficulties falling asleep (31.1%)

Difficulties falling asleep (27.1%)

The number in parentheses indicates the percentage of students who listed the issue among students who felt they suffered from sleep insufficiency.

Taking these facts together, young people in Japan are likely to suffer from both daytime sleepiness and nocturnal insomnia. In Japan, it was reported that sleep insufficiency was the main cause of daytime sleepiness in junior high school students, and that inappropriate sleep habits, such as low physical activity level and television viewing, were the potential responsible factors [24]. Exercise is important for good sleep hygiene [25], and an association between the duration of television viewing and irregularity of sleep habits in young children has been described [26]. Television viewing during childhood and adolescence has been associated with increased weight, poor fitness, smoking, and increased cholesterol in adulthood [27]. Watching television, along with playing videogames for an extended period of time, were significantly associated with prolonged sleep onset latency, as well as poor sleep hygiene and an insufficient amount of sleep [28]. Lack of sleep increases body weight [29]. Overweight individuals tend to be less physically active, and reduced physical activity, in turn, exacerbates weight gain. Reduced physical activity and excessive media exposure are likely to be factors that increase inadequate sleep hygiene, which can result in insomnia leading to sleep deficiency and daytime sleepiness.

In addition, the lack of discipline in the home and in public education system, as well as shopping centers that are open 24 hours per day and mobile phone, might contribute to poor sleep hygiene. Data obtained from 17,465 university students, aged 17 to 30 years, that were taking non-health-related courses at 27 different universities in 24 countries, revealed that both male and female students in Japan exhibited the shortest sleep duration and the highest rate of self-rated unhealthiness [30]. In addition, according to the study performed by Walt Disney Studio Home Entertainment in 2008, sleep duration of individuals aged 18-64 years was shortest in Japan, from the 17 countries evaluated [31]. I wonder that most adults, including parents in Japan, do not view sleep as a valuable behavior and, therefore, neglect sleep, which might lead to increased prevalence of inadequate sleep hygiene among the younger generation.

The major complaints of elementary school and junior high school students in 2001 in Tokyo [10] are listed in Table 2. Most of these complaints were consistent with symptoms described as associated features of behaviorally induced deficient sleep syndrome (irritability, concentration and attention deficits, reduced vigilance, distractibility, reduced motivation, anergia, dysphoria, fatigue, restlessness, lack of coordination, and malaise) in the International Classification of Sleep Disorders-2 (ICSD-2) [32]. Can these complaints, however, be explained by sleep insufficiency?

Table 2. Major complaints of students (>20%) [10]. 

Elementary school students

Persistent need to yawn (62%), desire to sleep (58%), desire to lie down (47%),

Eyestrain (33%), difficulties to sit straight (29%), memorizing difficulties (28%), irritated (27%),

Neck stiffness (26%), low activity (25%), difficulties to concentrate (25%),

Hypersensitive (24%), thirsty (21%), make many mistakes (20%)

Junior high school students

Desire to sleep (boys/girls; 73.8%/80.8%), persistent need to yawn 43.6%/69.1%),

Desire to lie down (43.2%/47.2%), eyestrain (40.7%/44.7%),

Memorizing difficulties (35.2%/33.6%), neck stiffness (29.3%/35.1%),

Lumbago (26.5%/23.2%), low activity (21.3%/28.0%),

Hypersensitive (20.0%/27.0%), difficulties to concentrate (21.0%/23.8%),

Irritated (20.5%/24.2%),

As mentioned previously, bedtime delay in youngsters reduces total daily sleep duration [8], and approximately 80% of kindergarten and nursery school teachers reported that many children are sleep-deprived [20]. In fact, sleep deprivation has been demonstrated to exert a negative effect on daytime functions [33-35], general well being [36], metabolic and endocrine function [37, 38], and body weight [29]. However, the required sleep duration of an individual person is very difficult to determine, because the need for sleep is variable and depends on several factors [39]. Adults normally sleep for varied lengths of times, and such habits are considered to develop at a young age [32]. Of course, these differences should not mean that one should not take care of their sleep duration. If individuals are alert and active during late morning, then they are more likely to have healthier sleep duration, sleep quality, and life rhythms.

Nocturnal Lifestyles and Behaviors

Not only a shortage of sleep duration, but also delayed bedtimes and wake-up times are known to produce physical, mental, and/or emotional problems.

Adults and Older Children

Later bedtimes and wake-up times are significantly associated with sub-clinical manic-type symptoms among working adults [40], and evening-type medical school students are reported to experience reduced sleep efficiency compared with morning-type students [41]. To determine if an individual is a morning-type or evening-type person, a self-assessment questionnaire was used. According to an original report [42], morning-type people went to bed and arose significantly earlier than evening-type people. Evening-type young adolescents in Taiwan exhibited a greater association with mood and anxiety symptoms [43]. Among 6631 adolescents aged 14.1-18.6 years, evening-types were found to exhibit more attention problems, perform more poorly in school, experience more injuries, and were emotionally upset more often than the other chronotype individuals [44]. Japanese junior high school students, with an evening preference, were reported to be more likely to exhibit poorer sleep-wake parameters and lifestyle habits than those with a morning preference [45], and there was a greater association between evening-type individuals and impulsivity in students [46]. Compared with morning-type students, evening-type 12- to 13-year old students were reported to be more likely to exhibit behavioral/emotional problems, suicidal behavior and ideation, and habitual substance use [47]. Evening-type children aged 8-13 years have been shown to exhibit a greater tendency towards antisocial behavior, rule-breaking, attention problems, conduct disorder symptoms in boys, and aggression towards others in girls [48].

According to a nationwide survey, students in Japan with regular bedtimes and waking times showed better school performance than those with irregular sleeping times [49]. And conversely, an irregular lifestyle is known to be associated with delayed bedtimes and waking times. Of the college students surveyed, those with poor sleep quality exhibited less regularity in social rhythms relative to those with good sleep quality, and later rising times and bedtimes were reported to be associated with worse sleep quality [50]. Moreover, in adult populations, evening-type people are reported to demonstrate a more irregular daily lifestyle than morning-type people [51].

These reports all suggest an association between delayed waking times, bedtimes and irregular lifestyle with problematic behaviors of older children, adolescents, and adults.

Studies on Preschoolers

Although few studies have described an association between sleep habits and behavior in preschoolers, problematic behaviors among children aged 4 to 6 years have been associated with late and irregular waking times and bedtimes, but not with sleep duration [52].

Suzuki et al. [53] compared the relationship between a 2-week sleep diary and the ability to copy a triangular figure on the first attempt in 222 children aged 5 and 6 years. The children who successfully copied the triangle had significantly earlier mean morning wake-up times, as well as significantly longer mean total sleep duration, compared with children who failed to copy the triangle. Compared with children with regular sleep-wakefulness rhythms, children with irregular sleep-wakefulness rhythms exhibited a 5.9-times greater risk of inability to copy the triangle. A semi-structured interview with 16 teachers identified 48 troublesome episodes in 42 children. The rate of children with irregular sleep-wakefulness rhythms among the children with the troublesome episodes (19/42) was significantly greater than children without troublesome episodes (15/180). These results suggested that children with irregular sleep-wakefulness rhythms exhibit more behavioral problems, as well as problems with integration of cognitive and motor activity.

In a separate study, 204 children, aged 12-40 months (mean 22.6 months), were assessed for daily average physical activity counts per minute (PA) [54]. Results showed that increased age, male gender, and early wake-up times exhibited significant positive correlations with PA. Among children with a mean age of 7.3 years, higher mean daytime activity counts were reported to be associated with a decrease in sleep latency [55].

Nocturnal Lifestyle and Neurological Systems

The above-mentioned studies on preschoolers, along with previously cited papers on older children, adolescents, and adults, report problematic behaviors that are associated with delayed wake-up times, delayed bedtimes, and an irregular lifestyle. Although delayed bedtimes also resulted in sleep loss [8], problematic behaviors were found to be more likely associated with delayed wake-up times, delayed bedtimes, and an irregular lifestyle, regardless of sleep duration [52]. In the following section, the presumed neuronal mechanisms associated with these results will be addressed.

Biological Clock

Circadian signals are relayed from the SCN to the hypothalamic dorsomedial nucleus via the subparaventricular zone. The dorsomedial nucleus of the hypothalamus combines inputs from the SCN with inputs from other areas, allowing for flexible control, and sends signals to structures that regulate various circadian rhythms, such as feeding, locomotion, sleep-wake alternation, corticosterone secretion [56], and the autonomic nervous system [57]. Typically, the endogenous period of the circadian clock is longer than 24 hours, and it is through exposure to sunlight in the morning people become accustomed to the 24-hour cycle [58]. Conversely, light exposure at night delays the circadian clock phase [58], or disrupts its function [59-61]. Non-photic cues, such as eating times [62] and activity [63], also serve to synchronize the circadian system to a 24-hour day. In the absence of time cues, daily rhythms become altered, developing their own rhythm. After spending life under such conditions for a considerable period of time, the staging of various biological rhythms changes, such as sleep-wakefulness and temperature [64]. Under such conditions, reciprocal phase interactions within circadian rhythms are disturbed. In general, most people spontaneously awake in the morning when the body temperature begins to rise from its lowest level and, conversely, fall asleep at night when the body temperature begins to decline from its highest level. However, once this reciprocal interaction is impaired, the phase relationship between body temperature and sleep-wake circadian rhythms is disrupted [64], known as circadian desynchronization [65, 66]. This condition might produce various physical and mood disturbances (disturbed nighttime sleep, impaired daytime alertness and performance, disorientation, gastrointestinal problems, loss of appetite, inappropriate timing of defecation, excessive need to urinate during the night). Similar complaints and mood alterations have been observed in patients with jet lag [67], seasonal affective disorder [68], and in astronauts [69].

Endogenous phasing of the circadian biological clock in morning-type individuals varies from evening-type individuals [70], who experience a temperature rise later in the morning and later waking times [71]. Moreover, individuals who are alert in the morning experience an earlier circadian rhythm temperature peak than do individuals who are alert in the evening [72]. These reports suggested that evening-type individuals suffer from circadian desynchronization [65, 66]. Those with delayed waking times and bedtimes, and an irregular lifestyle (an evening preference) are hypothesized to suffer from circadian desynchronization.

Arendt et al. [67] showed that jet lag recovery rate, which is attributed in large part to temporary circadian desynchronization, varies with individuals, as well as with the direction of time zone change. The susceptibility for developing symptoms, presumably due to desynchronization, is likely to vary in different individuals. In this regard, the following reports suggest that desynchronization susceptibility is affected by biological background.

Nilssen et al. [73] compared the prevalence of sleep disorders in two ethnically different populations living in the same extreme arctic climate. More than 50% of the Norwegian population in these studies [73, 74] resided in the northern region of Norway, whereas the Russian subjects were primarily recruited from the southern part of Russia and the Ukraine. The study determined that Russians exhibited a greater prevalence of sleep disorders than Norwegians. A one-year prevalence of self-reported depression was also compared in the two populations [74], with similar results. The authors [73, 74] postulated that insufficient acclimatization after migration to the north resulted in these effects. Susceptibility to these symptoms was presumably due to desynchronization, which was likely affected in part by unknown biological background factors, including acclimatization. However, acclimatization cannot be altered within one generation.

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