Mice Study Suggests Some Disorders May Be Tied to 4-Hour Cycles

A new animal study finds that four-hour cycles driven by the neurotransmitter dopamine may be implicated in the disturbed sleep-wake cycles of some mental disorders such as bipolar disorder and schizophrenia.

The study, led by Kai-Florian Storch, Ph.D., of the Douglas Mental Health University Institute and McGill University, has been published in the online journal eLife.

It is common knowledge that our daily sleep-wake cycle is governed by an internal 24-hour timer, the circadian clock. But researchers believe there is evidence that daily activity is also influenced by rhythms much shorter than 24 hours.

These rhythms are known as ultradian rhythms and follow a four-hour cycle. This cycle is frequently displayed in infants before they are able to sleep through the night.

Moreover, ultradian rhythms may explain why, on average, we eat three meals a day that are relatively evenly spaced across our daily wake period.

These four-hour ultradian rhythms are activated by dopamine, a key chemical substance in the brain, according to researchers. When dopamine levels are out of balance — as is suggested to be the case with people suffering from bipolar disease and schizophrenia — the four-hour rhythms can stretch as long as 48 hours.

In the study, genetically modified mice were used to demonstrate that sleep abnormalities, which in the past have been associated with circadian rhythm disruption, result instead from an imbalance of an ultradian rhythm generator based on dopamine.

The team’s findings also offer a very specific explanation for the two-day cycling between mania and depression observed in certain bipolar cases.

Researchers believe the cycle is a result of the changes in dopamine that occur on a 48-hour cycle.

The research is groundbreaking, they said, not only because of its discovery of a novel dopamine-based rhythm generator, but also because of its links to psychopathology. This new data suggests that when the ultradian arousal oscillator goes awry, sleep becomes disturbed and mania will be induced in bipolar patients.

Researchers believe oscillator imbalance may also be associated with schizophrenic episodes in schizophrenic subjects. The findings may have implications for the treatment of bipolar disease and other mental illnesses linked to dopamine dysregulation, they said.

Source: Douglas Mental Health University Institute/EurekAlert