A large body of literature describes all the possible consequences of living against the clock. These consequences can be divided into three categories. Emotional, Cognitive, and Somatic responses. As we will cover in more detail later, living against the circadian clock is often associated with sleep loss. We all know the emotional consequences of having slept too little. We are exhausted and irritable, our mood fluctuates, and we are impulsive. We suffer more easily from anxiety or depression and get easily frustrated and angry. And we are more clumsy. We tend to use both more uppers like caffeine and nicotine, and more downers, such as sedatives, sleep pills, or red wine. Discrepancies between internal and external time and the resulting sleep loss leads to a reduction in practically all cognitive functions ranging from lower concentration, decreased performance, and potential to worse memory capacities. We are not as good at multitasking or decision making. Our creativity and productivity suffers and we have less social competence. Challenging our circadian system also leads to a variety of somatic problems. Besides all the symptoms of sleep loss, we can have sensations of cold and even of pain. Our risk to develop almost any disease is increased ranging from cardiovascular and metabolic abnormalities to different forms of cancer. Both our immune and endocrine systems are affected, with all the potential consequences. Let's look at the effects of circadian dissonance on sleep. I would like to begin by reviewing different sleep patterns. The grey area in this graph represents a 12-hour equinox night from sunset to sunrise, flanked by 6 hours of daylight on each side. The first blue bar represents "normal sleep". Sleep onset around midnight and sleep end is around the time between 7:00 and 8:00, which gives us a sleep duration also between 7 and 8 hours. This sleep pattern is most probably quite "modern", because experiments have shown that people sleep more symmetrically around the mid-dark phase and can expand their sleep duration way beyond eight hours, when they are not allowed to use artificial light. You have seen in the lecture about human clocks that sleep duration has a wide distribution in the population. We therefore have to consider short sleepers as well as long sleepers as additional sleep patterns. Independent from sleep duration is sleep timing. As we have discussed in detail earlier in this course. What could be simply considered at being at the right end of a chronotype distribution is considered a "syndrome" or even a "disorder" by sleep clinicians. According to this diagnostic scheme, someone who sleeps much later than the general population is considered to suffer from DSPS, or Delayed Sleep Phase Syndrome. At the other end of the distribution, those people who sleep much earlier than the general population are diagnosed to suffer from ASPS, or Advanced Sleep Phase Syndrome. There is no doubt that both extreme chronotypes can have great difficulties to function normally in our society. And therefore should be entitled to medical help. However, the amount of suffering will also depend on geographical location and culture. Here, we compare the chronotype distribution of the Indian population in our database with that of Europeans, or US Americans. You can see that an extreme early chronotype, who probably would be diagnosed as an ASPS patient in the US or in Europe, would be in good company in India. One should not evoke quantitative cut-offs or thresholds to distinguish between "normal" and "abnormal" because the actual timing of the chronotype distribution depends on location and culture. The next sleep pattern is that of irregular sleep. Which can have a host of different causes, such as old age, obstructive breathing, or many other sleep pathologies. The circadian clock may also be the cause of irregular sleep. Sleeping at the wrong internal times may lead to more sleep interruptions, as can be the case in shift-workers. Other circadian reasons would be if the functioning of the SCN was disrupted for example by a haemorrhage or a tumor. Another sleep pattern refers to non-24-hour sleep, people who basically have no sleep problem but who's circadian clock is not entrained. Some blind people are not entrained to the 24-hour day despite a regular life involving work, meals and exercise. To understand why only some and not all blind people suffer from this problem, we have to add an important bit of information to understanding light entrainment in mammals. The mammalian clock can only be influenced by light via the retina in the eyes. As you probably know, several dedicated light receptors allow us to form images that help us to analyse our environment visually: The rods that allow us to see in low-light conditions and the different cones that allow us to see colour. At the end of the last century, circadian researchers wanted to know which of these receptors were crucial for circadian light entrainment. A series of ground-breaking experiments showed that light entrainment was still possible without cones and without rods. This surprising result led to the discovery of an additional light receptor in the retina that was hitherto unknown to eye researchers. This light receptor also involves an opsin which is involved in cones and rods and other receptors to detect light. But this so-called "Melanopsin" had a different structure and was not part of a dedicated receptor cell. Melanopsin is found in a special group of ganglion cells, and these light receptive Ganglion cells are directly connected to the SCN. With this knowledge, you can now understand my statement that only "some blind people are not entrained to the 24-hour day". Those blind people, who have no conscious visual perception may still have a functional Melanopsin System that allows their circadian clock in the SCN to entrain to the 24-hour day. Only those blind people, who have also lost light reception in the Melanopsin System are prone to be un-entrained despite a normal regular life. These patients have periodic sleep problems. If their clocks runs free with a 25-hour period, their internal time will shift an hour per day in reference to the external time. After 12 days, they are 180 degrees out of sync with the outside world and another 12 days later, they are for some days in sync again. Like in shift-workers, their sleep is usually interrupted and irregular on their out-of-sync-days, while it is quite normal during their in-sync-days. In summary, almost all challenges that lead to "circadian dissonance" will also result in some type of sleep deprivation or perturbed sleep. Let's now take a closer look why circadian dissonance also leads to metabolic problems. You have just seen this graph showing the activity of somebody who travels many timezones to the East. Experiments have shown that the SCN- controlled circadian system re-entrains gradually to the new light-dark cycle. A thumb rule for humans is approximately one day per each hour time change. If we start to eat at the usual local time after arrival at the destination, the liver clock will adjust much faster. This suggests that all situations of circadian dissonance -jetlag, social jetlag and shift work- may be associated with what biologists call "internal desynchrony". This refers to significant relative changes among different parts of the circadian programme, such as circadian rhythms in the liver and those in the brain. Some subjects who lived in the bunker -which you have encountered several times during this course- showed a signficant desychrony between basic physiological parameters -such as the core body temperature rhythms- and their sleep-wake cycle. While the physiological rhythms showed a period of approximately 25 hours, the period of the sleep-wake cycle could be as long as 48 hours. Thus, circadian dissonance can also lead to internal desynchronization. The part of the circadian system that regulates our individual sleep-wake cycle may get out of phase with the liver metabolism, when we are forced to be active against our internal time. For example, social jetlag makes most of us increase weight in a dose dependent manner. The metabolic problems could be a direct consequence of internal desynchronisations but they also could be caused by the fact that we eat at the wrong time. Studies have shown that we can more easily lose weight, if we shift our meal times earlier into the day -despite the same amount of consumed calories. The table of potential consequences lists stimulus consumption under emotional responses. One could argue that some of these are physiological medication to let us fall asleep before our individual sleep window opens and to make us alert despite of being woken in the middle of our subjective night. The more social jetlag people are exposed to, the more likely they are smokers, the more alcohol they drink, and the more caffeine they consume. [SOUND]
