Remember that Friends episode, when Chandler fell asleep at a meeting and ended up with a job in Tulsa? How about the time the bus driver had to wake you up at the end of the line, or that high school teacher who always fell asleep during detention? It happens to the best of us, most often when meetings are called for in the afternoons and when the caffeine is not in abundance. We are quick to blame big meals, not enough sleep or lack of exercise for our afternoon slump, but what about genes? Our genes can most definitely influence how much sleep we need, and in the extreme cases, genetic differences can even lead to sleep disorders. Narcolepsy is one such example, when genetic changes in one gene, HLA-DQB1, increase the risk of developing a disease that affects the balance between sleep and wakefulness.
Sleep is one aspect of our biology that still remains a mystery even to scientists. Depending on how long we sleep, we go through four to six separate cycles of sleep. Each cycle lasts about 100-110 minutes with two phases called non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. We enter REM sleep about 70-90 minutes after falling asleep and during REM sleep the brain becomes active. During this stage, we experience temporary muscle paralysis and we dream. People with narcolepsy enter REM sleep just a few minutes after falling asleep, which helps to explain the symptoms associated with narcolepsy – sleep paralysis, vivid hallucinations and collapsing into a sleep-like state while remaining conscious (cataplexy). Have you ever woken up in the middle of a bad dream, unable to scream or move? If you have, that very brief moment of sleep paralysis and cataplexy was probably enough for you to realize how terrifying the symptoms of narcolepsy can be. Even with their involuntary daytime naps, people with narcolepsy are sleep-deprived, because their night sleep is interrupted by frequent awakenings.
One way to diagnose narcolepsy is by looking at the levels of the neurotransmitter hypocretin (also called orexin), a chemical produced in the brain that controls alertness and prevents REM sleep. Individuals with cataplexy have lower levels of hypocretin because the nerve cells (neurons) that produce hypocretin die off overtime. Over 90% of these patients also have genetic changes in one gene, HLA-DQB1, which is thought to play a role in regulating hypocretin levels. The HLA-DQB1 gene normally encodes a protein that is involved in signalling the immune system against foreign bodies (e.g. bacteria and viruses). However, a different version of HLA-DQB1 gene encodes a protein that may recognize the hypocretin-producing cells as being foreign and signals for them to be killed. Genetic changes in HLA-DQB1 predispose individuals to narcolepsy, increasing the risk of developing narcolepsy by 7- to 25-fold.
More than 250,000 Americans have narcolepsy, but only 25% of these cases are accurately diagnosed, because it is often mistaken for depression, epilepsy or bipolar disorder, or simply dismissed as laziness. Cataplexy can be triggered by just an emotion, and it can be extremely dangerous in some situations, like driving or crossing the street. Adding insult to injury, a long list of health risks, including high blood pressure, obesity and decreased resistance to viral infections, are also associated with sleep-deprivation. There is no cure for narcolepsy, but the symptoms can be managed through medications that improve the level of alertness. A large proportion of us don’t get the recommended eight hours of sleep a night and are most likely sleep-deprived, but to experience what a non-medicated narcoleptic feels like every day, we would have to stay awake for two to three days straight. So, the next time you see that colleague who has trouble staying awake at meetings, and you think they are just lazy, you might want to stop and consider how different your life might be if you had narcolepsy.