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Desynchronized body timers may lead to abnormal “ups” and “downs” in psychiatric disorders

Posted February 17, 2015

Most living beings, such as ourselves, respond well to routine – we usually sleep and wake in regular intervals, which depend on the 24 hour light and dark cycle; we have daily energetic or idle periods; we get hungry and fulfill other natural needs at predictable times. Disruption of our internal clocks often lead to health issues, including cognitive problems and mood disorders. But does it all come down to the one master clock, or does our body keep many timers going at the same time?

Credit: martinak15 via Flickr (CC BY 2.0)

Credit: martinak15 via Flickr (CC BY 2.0)

The central pacemaker – SCN – is famous for driving our circadian rhythms and keeping us in line with a 24 hour cycle. However, growing body of research suggests that ultradian, i.e. “faster”, clocks of the body, which cycle at 2-6 hour intervals, not only operate in addition to, but can persist completely independently of the master circadian clock.

Ultradian rhythms are known to be involved in most daily physiological activities, including alertness, activity and sleep patterns, appetite and internal bodily changes, such as temperature and hormone fluctuations. In spite of their physiological importance, the mechanisms behind these regulators are not well understood.

Recent research published on eLife has found that complete removal of the central pacemaker or any day/night cues does not interfere with regular ultradian rhythms, suggesting alternative timers are still running in the body even if the master clock is broken for any reason at all. Instead, these rhythms greatly depend on dopamine signaling in the brain.

Dopamine is well-known for its role in pleasure and motivated reward. However, as research now shows, it also largely responsible for setting our internal clocks straight. In fact, while normal dopamine regulation causes regular bursts of activity every ~4 hours, overstimulation (e.g. after using methamphetamine, or when other elements in the system go out-of-whack) is likely to extend these intervals, and in extreme cases lead to “free-running” alertness cycles of up to 48 hours.

Curiously, such circabidian (48 hr) or “free-running” behavior patterns have been observed in schizophrenic patients; abnormal length “up” and “down” (manic and depressive) periods are also characteristic of bipolar disorder.

While previously attributed to circadian rhythms, these findings suggest that mood and other psychiatric disorders might develop due to desynchronization of dopamine-dependent ultradian timers, rather than the master clock. As such, genes and pathways involved in the system might make promising new targets for treatment, and help to make these debilitating conditions that much more manageable.

Written by Eglė Marija Ramanauskaitė

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