The trouble with sleep

We all need sleep – but what happens when sleep goes wrong? Laboratory News investigates

Is sleep an evolutionary mechanism developed to keep us out of harm’s way in the dark hours, or is it way to repair and recuperate after the day before? Scientists are still unsure exactly why we sleep, but they can agree that sleep is an essential part of our day.

Lack of sleep can be incredibly dangerous – ten rats subjected to long-term total sleep deprivation in 1989 died within 11-32 days, with no obvious anatomical cause of death¹. The rats had a debilitated appearance, lesions on their tails and paws, and lost a considerable amount of weight. While it is impossible for humans to be completely deprived of sleep over long periods – the brain shuts down and takes microsleeps, falling into a sleep state for a period of up to 30 seconds – sleep deprivation can affect the brain and cognitive function, leading to other problems.

Professor Francesco Cappuccio from the University of Warwick was part of a team that – together with researchers from University College London – found lack of sleep is associated with a doubling in the risk of death from cardiovascular disease. In 2007, researchers found that reducing sleep from seven to five hours doubled the risk of death from cardiovascular problems among their participants – 10,308 civil servants².

“Sleep represents the daily process of physiological restitution and recovery, and lack of sleep has far-reaching effects,” Cappuccio said. “Fewer hours sleep and greater levels of sleep disturbance have become widespread in industrialised societies. This change, largely the result of sleep curtailment to create more time for leisure and shift-work, has meant that reports of fatigue, tiredness and excessive daytime sleepiness are more common than a few decades ago.”

Interestingly, too much sleep also increased mortality. Individuals who increased their sleep to eight hours or more a night were more than twice as likely to die as those who had not changed their habit, but not from cardiovascular-related diseases.

Cappucio’s team concludes that sleeping around seven hours per night is optimal for health and a sustained reduction may predispose to ill-health, but some people find sleeping for this amount of time hard to achieve.

To understand what causes sleep deprivation, we have to understand what actually happens during sleep. Our sleep cycle is controlled by the circadian clock, which works with adenosine to inhibit the bodily processes associated with being awake. The body produces adenosine throughout the day, and high levels cause sleepiness. It also causes the release of melatonin and a decrease in the level of serotonin – together these two neurotransmitters are key in maintaining our sleep cycle.

Sleep is characterised by an absent – or much reduced – consciousness and inactivity of voluntary muscles. It cycles between two broad types – REM and non-REM, each of which has distinct physiological/neurological and psychological features.

Non-REM sleep
N1	Drowsy sleep with sudden twitches where the brain waves begin to change
N2	Characterised by sleep spindles or sudden bursts of energy in the brain
N3	Deep or slow sleep
REM	Accounts for around 20-25% of an adult’s total sleep, and is where most of our memorable dreaming takes place

These sleep cycles can be disrupted, sometimes due to medication; sometimes it’s a deeper neurological condition like Restless Leg Syndrome (RLS) or Willis-Ekborn disease. RLS is a neurological disorder where sufferers have an irresistible urge to move their body – usually the legs but sometimes the arms, torso and even phantom limbs – to stop uncomfortable or odd sensations. Sufferers describe the sensation as an itching or tickling they just can’t relieve, and liken it to the urge to yawn – just in their limbs.

The desire to move often starts and intensifies during wakefulness – particularly when relaxing – and while walking or stretching can bring about temporary relief, sufferers still get limb jerks during sleep that they’re completely unaware of.

“I could be sitting there watching TV and just all of a sudden need to get up and walk about,” said Simon Taylor, who developed RLS after being prescribed an antidepressant.

Simon also has ME and thought it was that which was causing him to feel tired all the time, but what he didn’t know was that he’d been twitching in his sleep.

“With ME you feel tired – a lot – but I was waking up feeling worse that I went to bed. It wasn’t until my wife mentioned I’d been jerking in my sleep for the last month that I began to look into it a bit more.”

The cause of Simon’s RSL was probably Prozac, a selective serotonin reuptake inhibitor (SSRI) antidepressant. Other medication, such as antipsychotics, antiemetics and antihistamines are also linked to RSL, although the exact causes are unknown.

Much of the research into the disease mechanism focusses on the dopamine and iron systems. These hypotheses are based on observations that iron and levodopa can treat RLS. Levodopa is a pro-drug – a drug given in an inactive form that when metabolised becomes an active pharmacological substance. Once it crosses the blood-brain barrier, it is metabolised in the brain into dopamine, raising the levels of the neurotransmitter, reducing symptoms and improving the overall quality of life.

Around 20% of cases of RLS are associated with iron deficiency; however, 75% of sufferers with RLS symptoms have increased iron stores. Other associated conditions include Parkinson’s disease – another dopamine-related disorder – varicose veins, foliate and magnesium deficiencies, and fibromyalgia, a condition related to muscle and tissue pain and fatigue.

Around 80-90% of people with RLS also have Periodic Limb Movement Disorder (PLMD) – a similar condition in which patients move their limbs involuntarily during sleep. They also have excessive daytime sleepiness, trouble going to and staying asleep.

Their limb movements occur at periodic intervals – around every 20 to 40 seconds – and usually during non-REM sleep. They can be anything from movement in the ankles or toes, to wild flailing limbs, but are again more likely to affect the legs than other limbs.

The condition can be difficult to diagnose as the causes are unknown, but the patient often has another underlying medical conditions such as narcolepsy or Parkinson’s disease, and the condition can be treated with anti-Parkinson’s medication.

Treatment for both RLS and PLMD is designed to reduce the symptoms and improve the overall quality of life. They are often tailored to the individual based on their symptoms and therapeutic response.

Insomnia is perhaps the most well-known sleep disorder. It is often thought of as a long-term difficulty in sleeping which causes functional impairment and stress during wakefulness, but the disorder encompasses a range of sleep problems from trouble going to sleep (sleep onset insomnia) to waking in the night and not going back to sleep, or waking too early (nocturnal awakenings). A sufferer’s poor sleep quality is down to not reaching the N3 stage of sleep, which has restorative properties.

The disorder can be actually be classified into three types ranging from transient insomnia to chronic insomnia. Transient insomnia lasts for less than a week and is usually caused by a change in the sleep environment – something as simple as a change in light reaching the room or a new smell. With acute insomnia, the sufferer fails to consistently sleep for a period of less than a month. If this carries on for more than a month, it is classified as chronic insomnia, and it can often be caused by another underlying disorder.

Some insomnias can be a result of medication, like fluoroquinolone antibiotics, psychoactive drugs or stimulants – like caffeine – or bought on by stress, fear and anxiety. It is often a symptom of an underlying mental health problem and in fact, half of all insomnia diagnoses are related to a psychiatric disorder. Mood disorders (depression and bipolar disorder), anxiety disorders (anxiety, panic disorders, post-traumatic stress disorders) and psychotic disorders (schizophrenia) can all play a role in affecting sleep, as can neurological conditions like Alzheimer’s or Parkinson’s.

Insomnia can also be linked to circadian rhythm disorders, where the internal body clock is out of sync with the external time cues. Shift work or jet lag can play a part, and treatment involves monitoring the behavioural and environmental factors that precede and interfere with sleep. Factors such as what time you go to bed, food eaten and exercise taken can all affect your ability to sleep.

So why is sleep important, why do we do it? There are many theories, but the truth is we don’t really know. It might be an evolutionary mechanism to help us recover from the day’s struggle or to keep us out of the way of predators, but what we do know is it is necessary. Interruptions in your sleep cycle – particularly if prolonged – can affect your overall health.

 References

1. Sleep deprivation in the rat: III. Total Sleep deprivation http://www.ncbi.nlm.nih.gov/pubmed/2928622
2. Researchers say lack of sleep doubles risk of death...but so can too much sleep http://www2.warwick.ac.uk/newsandevents/pressreleases/researchers_say_lack/

The author: Kerry Taylor-Smith is Web Editor for Laboratory News. She has a degree in Natural Sciences from the University of Bath.