Sleep Genes

Sleep is an active state of unconsciousness where the brain is responsive primarily to internal stimuli. It is an extremely complex process that is driven by the interaction between two largely independent basic mechanisms ¹:

• The circadian rhythm
• The homeostatic drive to sleep.

Sleeping from 7 to 8 hours per night is considered optimal for health, since, in cross-sectional studies, both shorter and longer sleep have been related to poor health outcomes, including obesity, heart disease, neuroticism, anxiety, and death.

Although it may seem obvious, the exact purpose of sleep has not yet fully been determined. Numerous theories exist ², such as:

• Inactivity theory

This theory is based on evolutionary pressure and suggests that creatures being inactive at night were less likely to die from the predation of injury in the dark.

• Energy conservation theory

This theory states that sleep reduces the energy demand during part of the day and night when it is least efficient to hunt for food and is supported by the fact that the body’s metabolism decreases by up to 10% during sleep.

• Restoration theory

This theory suggests that sleep allows for the body to repair and replete cellular components necessary for biological functions. This is also supported by the fact that several hormones are secreted during sleep.

• Brain plasticity theory

This theory is based on the notion that neural reorganization and growth of the brain’s structure and function occur during sleep.

These theories are not exhaustive and do not include all the relevant theories as to why sleep is so essential, however, a combination of these theories likely explains why humans cannot function without it.

Interestingly, research has shown that changes in gene expression occur during sleep and wakefulness cycles. Extended wakefulness causes increased energy expenditure in the brain and therefore multiple mechanisms are employed to limit the duration of wakefulness, resulting in limited energy expenditure. Research has found that ‘sleepiness’ begins when the expression of certain genes is increased to a point where their products accumulate, which is usually at the end of the day ³.

Factors responsible for regulating sleep

Although sleep and wakefulness cycles depend on the synchronization of numerous biological factors, they are a few main role players that affect our ability to become sleepy and finally fall asleep.

Melatonin

Melatonin secretion is stimulated by darkness and is inhibited by light. It, therefore, plays a central role in maintaining the circadian rhythm and prepares us for sleep when it gets dark. The receptor for melatonin in the brain has been observed to be prone to single nucleotide polymorphisms (SNPs) in its gene. Research has shown that SNPs in the gene of this receptor have been linked to sleeplessness and insomnia, as well as the risk of developing type II diabetes ⁴.

Adenosine

Adenosine is an end product of energy degradation that accumulates within our brain as the day progresses, or with prolonged wakefulness, and decreases during sleep. Interestingly, there’s a very close link between adenosine and melatonin; it was observed that the addition of adenosine onto brain sections of rats caused a significant release of melatonin ⁵. There is an enzyme that is responsible for degrading adenosine, and its function affects not only the adenosine levels in the brain but also melatonin production.

It is not surprising that studies have found that SNPs in the gene of this enzyme affect sleep quality. One study found that individuals possessing a particular SNP resulted in them having significantly higher evening melatonin levels as well as significantly better sleep quality. Individuals with a different SNP in this gene showed a significant relationship between insomnia and anxiety as well as insomnia and stress ⁶.

Adenosine also has a specific receptor that it binds to in the brain to exert its function. Interestingly, caffeine typically contained in coffee, tea, energy drinks, foods, and pharmaceuticals can inhibit or block this receptor. When this happens, the effect it causes is similar to that of insomnia. This is particularly true for individuals who have SNPs in the gene that codes for the adenosine receptor ⁷.

Glutamate

Neurotransmitters, which are molecules that activate the neurons in the brain, also have an important role in sleep/wake cycles. Glutamate is one of these neurotransmitters that is involved with the initiation and maintenance of these cycles and is also thought to regulate muscle tone during periods of wakefulness ⁸.

SNPs in genes associated with glutamate production or signaling have been linked to both mood disorders and sleep disturbances. Specifically, different SNPs in the glutamate receptor have been linked to longer or shorter sleep durations, depending on whether the individual possesses the major (dominant) or minor (recessive) allele ⁹. This study, as well as others, suggests that mood disorders and short sleep may share a common genetic background.