Humans show large inter-individual differences in organising their behaviour within the 24-h day—this is most obvious in their preferred timing of sleep and wakefulness. Sleep and wake times show a near-Gaussian distribution in a given population, with extreme early types waking up when extreme late types fall asleep. This distribution is predominantly based on differences in an individuals’ circadian clock. The relationship between the circadian system and different “chronotypes” is formally and genetically well established in experimental studies in organisms ranging from unicells to mammals. To investigate the epidemiology of the human circadian clock, we developed a simple questionnaire (Munich ChronoType Questionnaire, MCTQ) to assess chronotype. So far, more than 55,000 people have completed the MCTQ, which has been validated with respect to the Horne–Østberg morningness–eveningness questionnaire (MEQ), objective measures of activity and rest (sleep-logs and actimetry), and physiological parameters. As a result of this large survey, we established an algorithm which optimises chronotype assessment by incorporating the information on timing of sleep and wakefulness for both work and free days. The timing and duration of sleep are generally independent. However, when the two are analysed separately for work and free days, sleep duration strongly depends on chronotype. In addition, chronotype is both age- and sex-dependent.

This article reviews circadian thermoregulation in relation to sleep induction and phase of entrainment in the light of the comprehensive thermophysiological and chronobiological concepts of Jürgen Aschoff. The idea that temperature and sleep are interrelated is based on evolutionary history. Mammalian sleep developed in association with endothermy, and all species, independent of temporal niche, usually sleep during the circadian trough of their core body temperature (CBT) rhythm. The circadian pattern of CBT results from the balance between heat production and heat loss, the latter being relevant for sleep induction. Sleep under entrained conditions is typically initiated on the declining portion of the CBT curve when its rate of change and body heat loss is maximal. Body heat loss before lights off, via selective vasodilatation of distal skin regions, promotes sleepiness and the rapid onset of sleep. This thermophysiological effect represents the cement between the circadian clock and the sleep–wake cycle, and in turn determines phase of entrainment (?) and sleep onset latency (SOL). These interrelationships have been recently studied in a particular subset of the general population, mainly women, who suffer from cold hands and feet (the so-called vasospastic syndrome, VS). Women with VS exhibit not only a lower capacity to lose heat during the daytime but also a prolonged SOL, a disturbed ? of the circadian clock with respect to the sleep–wake cycle and psychologically, a disposition to turn experienced anger inwards. This naturalistic model leads us to a more general conclusion that regulation of distal skin blood flow may have clinical relevance for insomnia, in particular sleep onset insomnia.

Light exerts powerful non-visual effects on a wide range of biological functions and behavior. In humans, light is intuitively linked with an alert or wakeful state. Compared to the effects of light on human circadian rhythms, little attention has been paid to its acute alerting action. Here I summarize studies from the past two decades, which have defined and quantified the dose (illuminance levels), exposure duration, timing and wavelength of light needed to evoke alerting responses in humans, as well as their temporal relationship to light-induced changes in endocrinological and electrophysiological sequelae of alertness. Furthermore, neuroanatomical and neurophysiological findings from animal studies elucidating a potential role of light in the regulation of sleep/wake states are discussed. A brief outlook of promising clinical and non-clinical applications of lights’ alerting properties will be given, and its involvement in the design of more effective lighting at home and in the workplace will be considered.

Circadian rhythms in health and disease have most often been described in terms of their phases and amplitudes, and how these respond to a single exposure to stimuli denoted as zeitgebers. The present paper argues that it is also important to consider the 24-h regularity in the repeated occurrence of the zeitgebers. The effect of the regularity of stimulation by light, melatonin, physical activity, body temperature, corticosteroids and feeding on synchronization within and between the central circadian clock and peripheral oscillators is discussed. In contrast to the phase shifts that can be recorded acutely after a single zeitgeber pulse, the effects of irregularly versus regularly timed zeitgeber can be studied only in long-term protocols and may develop slowly, which is a possible reason why they have received relatively little attention. Several observations indicate a reciprocal relation between the robustness of the endogenous circadian timing system and its dependency on regularly timed zeitgebers. Especially at old age and in disease, proper functioning of the circadian timing system may become more dependent on regularly timed exposure to zeitgeber stimuli. in such conditions, regularly timed exposure to zeitgeber appears to be highly important for health. After a concise introduction on inputs to the central and peripheral oscillators of the circadian timing system, the paper discusses the responses of the circadian timing system and health to (1) a chronic lack of zeitgeber stimuli; (2) fragmented or quasi-ultradian stimuli and (3) repeated phase shifts in stimuli. Subsequently, the specific relevance to aging is discussed, followed by an overview of the effects of experimentally imposed regularly timed stimuli. Finally, a possible mechanism for the gradually evolving effects of repeated regularly timed stimuli on the circadian timing system is proposed.

This paper presents a clinical review of delayed sleep phase syndrome (DSPS) and non-24-h sleep–wake syndrome (non-24). These syndromes seem to be common and under-recognized in society, not only in the blind, but also typically emerging during adolescence. Both types of syndrome can appear alternatively or intermittently in an individual patient. Psychiatric problems are also common in both syndromes. DSPS and non-24 could share a common circadian rhythm pathology in terms of clinical process and biological evidence. The biological basis is characterized by a longer sleep period, a prolonged interval from the body temperature nadir-to-sleep offset, a relatively advanced temperature rhythm, lower sleep propensity after total sleep deprivation, and higher sensitivity to light than in normal controls.
There are multiple lines of evidence suggesting dysfunctions at the behavioral, physiological and genetic levels. Treatment procedures and prevention of the syndromes require further attention using behavioral, environmental, and psychiatric approaches, since an increasing number of patients in modern society suffer from these disorders.

The psychiatric intervention, light therapy, grew from an intensive 25-year research focus on seasonal affective disorder (SAD). Dosing and timing strategies have been honed to optimize the antidepressant effect, and efficacy relative to placebo has provided the evidence base for widespread implementation. A persistent question has been whether the model system for SAD has wider utility for psychiatric disturbance, even beyond depression. The circadian phase-shifting capacity of timed light exposure is universal, and chronobiological factors are at play across the disease spectrum. Recent promising initiatives extend to light treatment for nonseasonal major depressive disorder and bipolar depression, including drug- and electroconvulsive therapy-resistant cases. With light therapy, patients with antepartum depression may find an alternative to medication during pregnancy. Cognitive improvement under light therapy has been noted in adult attention deficit hyperactivity disorder. Motor function in Parkinson's disease has improved in parallel with the antidepressant effect of light therapy. The rest–activity disturbance of elderly dementia has been partially allayed under light therapy. In a new initiative, three major chronotherapeutic inventions—light therapy, sleep deprivation (wake therapy) and sleep time displacement (sleep phase advance therapy) are being combined to snap hospitalized patients out of deep depression and maintain long-term improvement.

Psychiatric chronotherapeutics is the controlled exposure to environmental stimuli that act on biological rhythms in order to achieve therapeutic effects in the treatment of psychiatric conditions. In recent years some techniques (mainly light therapy and sleep deprivation) have passed the experimental developmental phase and reached the status of powerful and affordable clinical interventions for everyday clinical treatment of depressed patients. These techniques target the same brain neurotransmitter systems and the same brain areas as do antidepressant drugs, and should be administered under careful medical supervision. Their effects are rapid and transient, but can be stabilised by combining techniques among themselves or together with common drug treatments. Antidepressant chronotherapeutics target the broadly defined depressive syndrome, with response and relapse rates similar to those obtained with antidepressant drugs, and good results are obtained even in difficult-to-treat conditions such as bipolar depression. Chronotherapeutics offer a benign alternative to more radical treatments of depression for the treatment of severe depression in psychiatric wards, but with the advantage of rapidity of onset.