Seasonal affective disorder (SAD) is a syndrome characterized by recurrent depressions that occur annually at the same time each year. We describe 29 patients with SAD; most of them had a bipolar affective disorder, especially bipolar II, and their depressions were generally characterized by hypersomnia, overeating, and carbohydrate craving and seemed to respond to changes in climate and latitude. Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave (delta) sleep. Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect.

Seasonal Affective Disorder: A Description of the Syndrome and Preliminary Findings With Light Therapy

1. In the first part of the paper, the model of non-parametric entrainment of circadian pacemakers is tested for the case of nocturnal rodents. The model makes use of the available data on freerunning period (τ) in constant darkness and on phase response curves (PRC) for short light pulses. It is tested in experiments using 1 or 2 light pulses per cycle. 2. Mesocricetus auratus and Peromyscus leucopus entrain to Zeitgebers involving 1 pulse (15' or 60') per cycle. The phase angle differences between rhythm and light cycle depends on the periods (τ and T) as predicted by the model. Entrainment of P. leucopus is unstable due to the after effects on τ created by the light pulse. 3. The limiting values of Zeitgeber period to which the animals entrain are much closer to 24 h than in Drosophila pseudoobscura, as the model predicts. However, frequent failures to entrain to T = 23 and T = 25 h are only explained if we take considerable interindividual variation in both τ and PRC into account. 4. With 2 pulses per cycle, the model predicts that entrainment will be more stable when activity is in the longer interval between the pulses than when it is in the shorter interval. This is true in the experimental data, where the phase relationships match predictions for skeleton photoperiods up to ca. 14 h. Increasing asymmetry forces animals into a "phase jump", so that activity shifts from the shorter to the longer interval. These ψ-jumps are accurately predicted in the hamster, but they occur at much longer photoperiods than predicted in P. leucopus. 5. Thus, the unqualified model, using a rigidly fixed species τ and PRC, is surely inadequate to explain entrainment. The extent to which variations in τ and PRC-shape, both "spontaneous" and induced by the entrainment process, can be known or inferred restricts the validity of the predictions. Yet we conclude, from a good deal of agreement between experiment and prediction (i), from the close correspondence between complete and skeleton photoperiods (ii), and on behavioural grounds (iii), that non-parametric entrainment by short light signals has a major share in the entrainment of nocturnal rodent rhythms in nature. 6. With these restrictions in mind, we analyse in the second part of the paper how the empirical regularities concerning τ and PRC contribute to the stabilization of the phase angle difference (ψ) between the pacemaker and the external world. Use is made of computer simulations of artificial pacemakers with variable τ and PRC. 7. ψ is most sensitive to instabilities in τ when ¯τ is close to 24 h. Thus the very circadian nature of these pacemakers helps to conserve ψ. Selection pressure for homeostasis of τ has been large in a species (M. auratus) where ¯τ = 24 h. The effect of ψ-instability is further reduced by entrainment with 2 pulses (dawn and dusk), made possible by the PRC's having both an advance and a delay section. 8. To analyze the contributions to ψ-conservation with seasonally changing photoperiod, we have assumed that it is of functional significance to conserve the phase of activity with respect to dusk (nocturnal animals) or to dawn (diurnal animals). We distinguish three contributions of nocturnal pacemaker behaviour to this type of ψ-conservation: increased amplitude of the PRC (i), asymmetry in the PRC, such that the slope of the delay-part is steeper than the slope of the advance-part (ii), and a short freerunning period in DD (iii). 9. A further contribution must derive from parametric effects of light, which are not traceable by the model, but certainly effective in preventing in complete photoperiods the ψ-jump which is seen in skeleton photoperiods. The existence of parametric effects is further demonstrated by the change of τ with light intensity in LL, described by Aschoffs Rule, which presumably reflects differences in PRC-shape between nocturnal and diurnal animals. 10. The paper concludes with an attempt to distinguish the features of circadian clocks that are analytically necessary for entrainment to occur (i), or have functional meaning, either in the measurement of the lapse of time (ii) or in the identification of local time (iii).

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A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. I. The Stability and Lability of Spontaneous Frequency

Human behavior shows large interindividual variation in temporal organization. Extreme "larks" wake up when extreme "owls" fall asleep. These chronotypes are attributed to differences in the circadian clock, and in animals, the genetic basis of similar phenotypic differences is well established. To better understand the genetic basis of temporal organization in humans, the authors developed a questionnaire to document individual sleep times, self-reported light exposure, and self-assessed chronotype, considering work and free days separately. This report summarizes the results of 500 questionnaires completed inapilotstudy.Individualsleeptimesshowlargedifferencesbetweenworkand freedays,exceptforextremeearlytypes.Duringtheworkweek,latechronotypes

/pdf/life-between-clocks-daily-temporal-patterns-of-human-2i1rqfyvgw.pdf

Life between clocks: daily temporal patterns of human chronotypes.

Biological rhythms and the behavior of populations of coupled oscillators

In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.

https://science.sciencemag.org/content/sci/288/5466/682.full.pdf

Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

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Exogenous and endogenous components in circadian rhythms.

Like many animals, humans have adjusted to the natural environment so as to be prepared for efficient activity during daytime and to rest at night. As the basis of this program, almost all structures and functions undergo regular changes within 24 hours. Such rhythms have been described in physiological parameters, such as hormone levels in blood plasma, blood pressure and heart rate, body temperature, and sleep propensity, and in behavioral parameters, such as mood, reaction time, computation speed, and performance in learning tasks. These rhythms normally keep distinct phase-relationships with each other, implying a high degree of internal temporal order. In principle, this rhythmicity is maintained when subjects are sleep deprived, when they are starved, or when they receive equal amounts of food at short intervals over the day. The timing of single meals, however, may influence the pattern of some variables, and the sleep-wake cycle can have phase-setting as well as masking effects on the instantaneous value of rhythms as especially known for body temperature and some hormones.

https://science.sciencemag.org/content/sci/148/3676/1427.full.pdf

Circadian rhythms in man.

As in other vertebrates, the human circadian system is characterized by a distinct temporal order of its components. This order is maintained by the coupling forces between various oscillators as well as by the entraining signals from the Zeitgebers (see Chapter 12). There is hardly a tissue or function that has not been shown to have some 24-hr variation. As an example, Figure 1 presents results of an experiment in which six subjects were held in groups of two on the same rigorous schedule. Although there were considerable interindi-vidual differences and also day-to-day variations, patterns like those shown in Figure 1 are satisfactorily reproducible. This reproducibility is again illustrated in Figure 2, which summarizes data on plasma Cortisol collected in six laboratories. To account for possible phase-controlling effects of sleep (see below), the curves are normalized with regard to the various sleep times of the subjects. Despite the fact that Cortisol, like many other hormones, is secreted in a highly variable sequence of episodes (see Chapter 12, Figure 1), a clear circadian pattern emerges in each curve, averaged from the data on n subjects, and there is perfect correspondence in phase and relative amplitude between the curves. It is noteworthy that two submaxima appear in all curves at about the same circadian phases. Presumably, they are not consequences of the usual meal timing but may represent a rhythm component interposed between the circadian domain and the episodes (cf. the discussion in Aschoff, 1979).

The Circadian System of Man

The article reviews most of the data available on the period ẗ of freerunning circadian rhythms, measured in constant conditions. Emphasis is placed on the effects of light intensity and ambient temperature on ẗ, with references to influences of other external as well as internal factors. In the introduction, examples are given of spontaneous and induced variations in ẗ and its dependence on the experimental history. The discussion concentrates' largely on results obtained from arthropods and vertebrates.

Circadian rhythms: influences of internal and external factors on the period measured in constant conditions.

Der Umsatz nuchterner, im Dunkeln sitzender Vogel hat einen ausgepragten Tagesgang; die Sauerstoffaufnahme liegt in der Aktivitatszeit (α) rund 25% hoher als in der Ruhezeit (ϱ) Eine Aufarbeitung der in der Literatur mitgeteilten Mesergebnisse zeigt, das es, zumindest bei Vogeln, moglich und sinnvoll ist, fur die Abhangigkeit des Umsatzes vom Korpergewicht zwei nach α- und ϱ-Werten getrennte Regressionsgeraden zu berechnen Es bleibt eine Frage der Ubereinkunft, ob man im Hinblick auf die Streuungsunterschiede zwischen α- und ϱ-Werten und im Wunsch nach ‚Minimal-Werten‘ kunftig zur Angabe des wahren Ruheumsatzes (Grundumsatzes) nur solche Werte zulast, die in ϱ gemessen sind

Jürgen Aschoff

Papers

Exogenous and endogenous components in circadian rhythms.

Circadian rhythms in man.

The Circadian System of Man

Circadian rhythms: influences of internal and external factors on the period measured in constant conditions.

Der ruheumsatz von Vögeln als Funktion der Tageszeit und der Körpergröße