Why do some people fall into a deep slumber the moment they get horizontal, while others go through  jittery, fitful sleep every night? Some are simply high-strung individuals; they just can’t relax, divorce their minds from any thought of their daily issues. We all experienced it sometimes; I almost invariably wake up several times a night if I have to catch an early flight the next morning, especially if I didn’t set up the alarm clock. But what about those unfortunates who are chronically sleep deprived despite their best efforts? A surprising clue came recently from a study on narcolepsy.

What is Narcolepsy?

According to the National Institute of Neurological Disorders and Stroke “narcolepsy is a chronic neurological disorder caused by the brain’s inability to regulate sleep-wake cycles normally. At various times throughout the day, people with narcolepsy experience fleeting urges to sleep. If the urge becomes overwhelming, patients fall asleep for periods lasting from a few seconds to several minutes. In rare cases, some people may remain asleep for an hour or longer.

Contrary to common beliefs, people with narcolepsy do not spend a substantially greater proportion of their time asleep during a 24-hour period than do normal sleepers. In addition to daytime drowsiness and involuntary sleep episodes, most patients also experience frequent awakenings during nighttime sleep. For most adults, a normal night’s sleep lasts about 8 hours and is composed of four to six separate sleep cycles. A sleep cycle is defined by a segment of non-rapid eye movement (NREM) sleep followed by a period of rapid eye movement (REM) sleep.

Scientists now believe that narcolepsy results from disease processes affecting brain mechanisms that regulate REM sleep. For normal sleepers a typical sleep cycle is about 100 – 110 minutes long, beginning with NREM sleep and transitioning to REM sleep after 80 – 100 minutes. But, people with narcolepsy frequently enter REM sleep within a few minutes of falling asleep.”

What causes narcolepsy?

The complete answer is still unknown, but what is known is surprising. A number of variant forms (alleles) of genes located in a region of chromosome 6 known as the HLA complex have proved to be strongly, although not invariably, associated with narcolepsy. The HLA complex comprises a large number of interrelated genes that regulate key aspects of immune-system function. The majority of people diagnosed with narcolepsy are known to have specific variants in certain HLA genes. However, these variations are neither necessary nor sufficient to cause the disorder. Some people with narcolepsy do not have the variant genes, while many people in the general population without narcolepsy do possess these variant genes. Thus it appears that specific variations in HLA genes increase an individual’s predisposition to develop the disorder-possibly through a yet-undiscovered route involving changes in immune-system function-when other causative factors are present.

What does the immune response have to do with sleep? There is no satisfactory answer yet. But let me point out that the nervous system exerts a strong influence on the immune response, and sleep deprivation has been shown to cause a decline in immunological activity and an increase in susceptibility to infection.

What about gene carriers who do not have narcolepsy?

This question was the subject of a study published in the October issue of Neurology. The study looked at people who have a gene variant that is closely associated with narcolepsy. However, having the gene variant, called DQB1 *0602, (which is part of the HLA complex, which is associated with the immune response) does not mean that a person will develop narcolepsy; depending on the population, 12 to 38 percent of those with the variant do not have the sleep disorder and are considered healthy sleepers. Also, people without the gene variant can develop narcolepsy, though this is less common.

For the study, 92 healthy adults without the gene variant were compared to 37 healthy adults who had the gene variant but did not have any sleep disorders. All of the participants came to a sleep laboratory. For the first two nights, they spent 10 hours in bed and were fully rested. The next five nights they underwent chronic partial sleep deprivation, also known as sleep restriction, where they were allowed four hours in bed per night. During the remaining time, lights were kept on and participants could read, play games, or watch movies to help them stay awake.

Researchers measured their sleep quality and self-rated sleepiness and tested their memory, attention and ability to resist sleep during the daytime. The people with the DQB1*0602 gene variant were sleepier and more fatigued while both fully rested and sleep deprived. Their sleep was more fragmented. For example, those with the gene variant woke up on average almost four times during the fifth night of sleep deprivation, compared to those without the gene variant, who woke up on average twice. Those with the gene variant also had a lower sleep drive, or desire to sleep, during the fully rested nights.

Those with the gene variant also spent less time in deep sleep than those without the variant, during both the fully rested and sleep deprivation nights. During the second fully rested night, those with the variant had an average of 34 minutes in stage three sleep, compared to 43 minutes for those without the variant. During the fifth night of sleep deprivation, those with the variant spent an average of 29 minutes in stage three sleep, compared to 35 minutes for those without the variant. The two groups performed the same on the tests of memory and attention. There was also no difference in their ability to resist sleep during the daytime.

What are the implications?

Millions of people suffer from sleep deprivation. People on night shifts are chronically sleep deprived, irritable, and tend to perform poorly on tasks that require concentration and quick decision making. Road warriors who fly across several time zones notoriously suffer from “jet lag”. And people with a lot on their mind, be it family problems, job pressures, or generally being “worry warts” –all are prime targets for the debilitating condition of sleep deprivation.

This study, albeit coming at the problem from the narcolepsy angle, is an important step in deciphering the puzzle of sleep and its disorders.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

1 COMMENT

  1. I agree, that sleeping disorders lead to various problems in health. It is important to single out the reason and to start a course of treatment if necessary.

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