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What are the Causes of Narcolepsy?

By D. Jeffress
Updated May 17, 2024
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Narcolepsy is an uncommon condition in which biological patterns of sleeping and wakefulness are poorly regulated by the brain. Sufferers are prone to excessive daytime sleepiness and quickly falling into deep slumbers where their muscles can become temporarily paralyzed. Despite many years of modern research, the exact causes of narcolepsy remain unclear. The disorder is almost certainly the result of specific genetic mutations, and recent studies have come close to pinpointing the genes involved and explaining how they trigger symptoms. In addition, several different environmental factors can increase the likelihood of developing the sleep disorder if the initial genetic causes of narcolepsy are present.

Most sleep experts believe the primary causes of narcolepsy are related to genetic mutations on chromosome six. A group of genes on the chromosome called the human leukocyte antigen (HLA) complex have been studied in depth. The HLA complex is primarily involved in maintaining immune system functioning in humans. In many people with narcolepsy, mutations on HLA genes appear to trigger autoimmune responses that attack neurons that carry hypocretin, an important chemical that promotes wakefulness. Without enough hypocretin, the brain is unable to maintain normal sleeping and waking patterns.

Other genetic causes of narcolepsy have also been identified. In studies on dogs, researchers found that chromosome 12 mutations can impair neural receptor sites for hypocretin. Instead of neural cell death, the lack of hypocretin is caused by an inability of neurons to absorb it. Ongoing research hopes to better elucidate the links between hypocretin, narcolepsy, and neural activity.

Genetics alone is usually not enough to trigger narcolepsy. Other factors such as traumatic brain injuries and tumors may impair the parts of the brain that regulate sleep cycles, consciousness, and muscle control as well. In particular, damage to the hypothalamus and the pons in the brain stem is closely associated with the expression of narcolepsy symptoms in some patients. Biological factors related to hormone imbalances and prolonged periods of stress may contribute to the disorder as well.

Environmental factors are also potential triggers or causes of narcolepsy for patients who are genetically predisposed to hypocretin shortages. Severe viral infections, smoking, exposure to pollutants, and poor dietary choices leading to obesity have all been correlated with narcolepsy symptoms. It is likely that future genetic research and clinical trials will uncover more information about the roles that mutations and environmental factors play in altering brain chemicals and leading to the expression of the disorder.

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