From Sleep Study, Clues to Happiness

A little over a decade ago, scientists discovered that narcolepsy, the neurological disorder that leads to episodes of irresistible sleepiness, is caused by the loss of brain cells that produce hypocretin, a neurotransmitter that promotes wakefulness.

But the discovery did not shed light on two other mysterious problems associated with the disorder. Narcoleptics have profoundly high rates of depression — up to six times the rate in the general population — and they have a tendency to collapse when swept by some emotions, a phenomenon known as cataplexy.

Now research shows that in addition to regulating sleep, hypocretin also appears to govern emotion, particularly experiences of joy and happiness.

The study has implications that extend beyond narcolepsy. It suggests that the brain has several different arousal systems, and that one of them, driven by hypocretin, has the specific function of keeping people awake for pleasure.

It also raises concerns that drugs that block hypocretin could potentially cause depression and other unexpected side effects. One such medication, a sleeping pill from Merck called suvorexant that works by blocking hypocretin, essentially causing narcolepsy for a night, is awaiting government approval.

The new research, published this month in the journal Nature Communications, involved a small group of patients with epilepsy who had special electrodes implanted in their brains that could directly monitor seizure activity and hypocretin levels around the clock.

“Apart from their seizure disorder, these patients were normal,” said Dr. Jerome Siegel of the V.A. greater Los Angeles Healthcare System, the study leader and a psychiatry professor at U.C.L.A. “They’re watching TV, they’re talking to their relatives, walking around the hospital, going to the bathroom. They’re not mentally handicapped in any way, and we are observing them with video and periodically asking them to complete forms indicating how they feel – whether they’re happy or sad, hungry or thirsty, in pain or not.”

Dr. Siegel, along with graduate student Ashley Blouin and their colleagues, expected to find that the ebb and flow of hypocretin mirrored the sleep cycle, rising in the morning and falling at night.

“But what we found was more complex,” Dr. Siegel said. “The maximal release of hypocretin was not really related to arousal in the usual way. It happened during waking for sure, but the maximal release was simply when people reported they were happy.”

The findings showed that hypocretin levels surged when the patients experienced joy and pleasure – while watching a favorite team win a baseball game, for example, or spending time with family. But when they experienced pain from their surgical implant, or anxiety about their medical situation, their levels of hypocretin fell. To read more from ANAHAD O’CONNOR, click here.