The weird science behind the antidepressant effects of sleep deprivation

We know poor sleep is often associated with deteriorating physical and mental health but for decades scientists have reported a strange phenomenon whereby acute sleep deprivation actually leads to antidepressant effects. For a short time following just one sleepless night depressed patients can sometimes experience an elevated mood. Even healthy people can relate to that loopy, punch-drunk feeling after pulling an all-nighter and running into the next day. Yevgenia Kozorovitskiy and a team of researchers from Northwestern University set out to investigate this odd physiological sensation.

“Chronic sleep loss is well studied, and its uniformly detrimental effects are widely documented, but brief sleep loss – like the equivalent of a student pulling an all-nighter before an exam – is less understood,” Kozorovitskiy explained.

To investigate exactly what happens in the brain after a night of acute sleep deprivation the researchers developed a unique experiment to keep mice awake for extended periods of time. The device they used consisted of a small platform a few centimeters above a slowly rotating beam circling the floor. If the mouse fell asleep it would topple off the platform and be awakened by the rotating beam. The goal was to create a situation where the animal could be kept awake without it being excessively stressed.

After a sleepless 12 hours the animals were seen to become hyperactive and hypersexual. These traits tended to disappear after a few hours but further tests designed to assess depressive states saw distinct antidepressant qualities from the sleepless night lasting up to three days. Further study revealed heightened activity in dopamine neurons were responsible for the behavioral changes in the mice.

“We were curious which specific regions of the brain were responsible for the behavioral changes,” said Kozorovitskiy. “We wanted to know if it was a large, broadcast signal that affected the entire brain or if it was something more specialized.”

Three particular brain regions seemed mostly responsible for the effects of sleep deprivation – the prefrontal cortex, the nucleus accumbens and the hypothalamus. Homing in specifically on the antidepressant effects, the researchers discovered dopamine neurons in the prefrontal cortex to be solely responsible.

Even more interestingly, the researchers discovered sleep deprivation apparently triggered a degree of synaptic plasticity in the prefrontal cortex. And it was this mechanism that generated the antidepressant effects in the mice.

Exactly why acute sleep deprivation causes this effect is still a bit of a mystery. Kozorovitskiy suggests the mechanism could have evolutionarily beneficial roots, helping sharpen up an animal for a short period of time when faced with a threat.

“You can imagine certain situations where there is a predator or some sort of danger where you need a combination of relatively high function with an ability to delay sleep,” speculated Kozorovitskiy. “If you are losing sleep routinely, then different chronic effects set in that will be uniformly detrimental. But in a transient way, you can imagine situations where it’s beneficial to be intensely alert for a period of time.”

It's hoped the new findings will point researchers in the direction of new therapeutics for mood disorders. Finding ways to pharmacologically harness this rapid antidepressant mechanism could be incredibly useful considering most current medicines take weeks to kick in.

Kozorovitskiy does stress these findings are not encouragement for depressed people to stay up all night as a way of bumping up their mood.

“The antidepressant effect is transient, and we know the importance of a good night’s sleep," she said. "I would say you are better off hitting the gym or going for a nice walk.”

The new study was published in the journal Neuron.

Source: Northwestern University