Welcome to the lecture dealing with pathologies associated with a malfunctioning circadian clock and the consequences of living against the circadian clock. On the behavioral level there are two sorts of living against the clock. One is associated with demands of the social external clock that force us to live against our biological internal clock. This concerns basically healthy people who gradually develop pathologies due to a chronic life against the clock. The other concerns people who are already ill or suffer from a pathology that appears to be associated with circadian qualities that differ from those of most healthy people. Let us first look at the discrepancies between the social and the biological type. We humans have to live by three clocks, the sun clock, the social clock and our biological, circadian clock. We have seen several examples throughout this course how these three time scales interact. In the great circadian experiment, students who lived a normal urban life were taken camping in Colorado far away from towns or settlements. During the days, they were exposed to very bright light. And during the nights, they had nothing but darkness. While the individual students were significantly different chronotypes in their normal urban life, they became almost the same chronotypes after a week of camping. A similar result has been reported for blackbirds, which either live in the countryside or in towns. During the camping week, the students also didn't live by the social clock, but by the sun clock since there wasn't much to do or to see once the sun had set. One could argue that under these very basic conditions, which simulated how humans lived early on in their cultural history, all three of these clocks coincided, did not show dissonance, but consonance. The blue and the red hands of the clock representing external and internal time overlapped. We have encountered several reasons why the two external clocks, sun clock and social clock, differ from each other and also why they can differ from the biological clock. I call this state, when the hands of the different timing systems don't overlap, circadian dissonance. This dissonance has often been termed circadian rhythm disruption or chronodisruption. But these terms rather describe the actions that lead to the dissonance, rather than the resulting steady state situation. Other terms that are commonly used are circadian alignment or misalignment. Personally, I prefer consonance and dissonance because we are talking of rhythms here that are either swimming together or apart. In the lecture on human circadian clocks in real life, I introduce you to the concept of social jetlag, which leads to the discrepancy between external and internal time. Close to 90% of the population shows marked differences in their sleep behavior between work days and work-free days. On work days sleep is usually terminated by an alarm clock. This concerns more than 80% of the population. Work day sleep is usually earlier and shorter than that on free days. We quantify the amount of social jetlag by comparing the mid-sleep times on work days with that those on free days. Again, the main reason for social jetlag lies in our light behavior. We have already covered this. But let's put some numbers to this statement by comparing daily life profiles of people living in different environments and different light conditions. This is a light exposure profile of an office worker in an urban environment. The maximum of this profile is around 6,000 LUX, a measure for the light intensity perceived by the human eye. This office worker is obviously able to go outside around lunchtime because one hardly ever averages more than 500 LUX within a building. This profile is quite representative for people living in urban settings of industrialized countries. Let's compare this profile with that of somebody who works outside during the day. This person reaches light exposures of 110,000 LUX. The flat blue profile is the one we just saw for the office worker but now scaled to the new farmer profile. Throughout the day modern man is exposed to approximately a thousandfold less light than our ancestors. But the large differences are not only present during the day. During the night this ratio is inverse. People who live without electricity are exposed to very little light after sunset, while most of us average a maximum of around 50 LUX in the evening even when it's already dark outside. Again the light profile just shown for the person living without electricity is redrawn with the same scale used for the modern light exposure. Low light during the day and dim light during the night weakened the time keeper, and as you have heard, this delays our clock. It should be noted that this statement is correct for the majority of human circadian clocks, namely for those that produce days longer than 24 hours in constant conditions. People who have clocks which produce shorter days become even earlier the weaker the time keeper, but they are very rare. If the demands of the social clock don't adapt to this delay, that is, if we still have to go to work at an early hour, social jetlag leads to circadian dissonance. An even more drastic form of social jetlag is found among shift-workers. Here you see an example of an activity of a shift-worker. The work schedules are shown as red boxes in the background. And the daily activity profiles are shown as brown traces. Every couple of days these workers have to be active at different times of the 24-hour day. And they have to try and sleep before they go to work or when they come home. If we highlight the sleep episodes as blue horizontal bars, you can see now how fragmented shift-workers sleep, especially after night shifts. This subject does not sleep at all after the last night shift shown here and recovers from the strong sleep loss on the next free day. While social jetlag concerns over 80% of the population, including workers as well as children and teenagers attending schools, its more severe form, rotating shift-work, concerns about 20% of the working population. A rarer, but well known form of circadian dissonance, is travel jetlag. This graph shows the activity profiles of someone who traveled nine time zones east. Note that all days of the recording are plotted in reference to the local time at the origin. Although it looks as if the activity profiles switch immediately, you know from the content we covered in the lecture about entrainment and circadian formalisms that the underlying circadian clock only gradually, while our so-called transients adapt to the new light-dark cycle. We will come back to this later. A good example of another type of circadian dissonance are large time zones. You have already seen this graph in the lecture on human clocks in real life. The bright green pixels indicate clocks that are very early within the time zone. Black pixels are intermediate, and red pixels are very late in reference to the time zone. The two longitudes, where midnight according to local time represents the middle of the night, are drawn as vertical lines for Greenwich Mean Time, or GMT, and for the Central European Time, or CET. We have already discussed the huge differences in internal circadian time between, for example, the Hungarians and the people from Galicia in northwest Spain. Even more drastic examples of large time zones that leads to circadian dissonances are parts of Russia and the entire area of China. [SOUND]
