Explanations of Narcolepsy

The main explanations for narcolepsy involve genes and the neurotransmitter orexin. It has been suggested that a defective gene on chromosome 6 is responsible for narcolepsy in humans, based on the identification of a defective gene on chromosome 12 responsible for narcolepsy in dogs. These genes code for proteins in the brain which act as receptors for orexin, which plays a role in the regulation of appetite, sleep and wakefulness. With these receptors functioning abnormally, regular orexin transmission cannot happen in the brain so it cannot properly control sleep behaviour - leading to the symptoms of narcolepsy such as excessive daytime sleepiness, cataplexy and sleep paralysis.

It is also suggested that narcoleptics transition straight into REM sleep from wakefulness rather than going through light sleep and slow wave sleep first, leading to the sudden loss of muscle tone in cataplexy and sleep paralysis; hypnogogic hallucinations represent dreams experienced in a state of semi-wakefulness.

Lin et al provided supporting evidence for the role of genetics in the development of narcolepsy. Using genetic analysis techniques, a gene mutation on the 12th chromosome was identified in dogs as being responsible for narcolepsy - on a gene which regulates orexin receptors. A similar mutation on the 6th chromosome was identified on a gene with the same regulatory purposes - these results would support the hypothesis that genetics and impaired orexin receptors may play a causal role in narcolepsy. 

Thannickal et al carried out research supportive of Lin's suggested role of orexin in narcolepsy. Scanning the brains of narcoleptics and healthy controls, they found a severely reduced quantity of orexin-producing cells in the narcoleptics compared to the control group - supporting the hypothesis of abnormally low orexin levels causing narcolepsy. However, determining the direction of cause and effect is a difficulty with these results - although the reduced density of orexin cells may have caused narcolepsy, the condition itself may have caused the reduction in orexin. Causation cannot be determined, weakening the validity of the supporting evidence.

However, research by Gordon et al supports a different explanation - of narcolepsy as an autoimmune disorder, rather than it being caused by genetics or orexin. Mice were injected with antibodies from the blood of either narcoleptics or non-narcoleptics - the group injected with narcoleptic antibodies developed the symptoms of narcolepsy. This suggests that narcolepsy is caused by our own antibodies malfunctioning and attacking brain tissue, challenging the genetic and orexin hypothesis.

On one level, Gordon's research can be seen as scientifically credible through its use of a control group. The use of one group injected with non-narcoleptic antibodies to compare the experimental group to allows cause and effect to be determined - we can be fairly sure that the injection of the antibodies led to the development of narcoleptic symptoms in the mice. However, the use of non-human animals is an issue here - neurological or immune differences between mice and humans may mean that it would be overly anthropomorphic and invalid to generalise the conclusions of this study to humans - narcolepsy may not work the same way in both species.

The orexin explanation of narcolepsy has valuable real world application in the use of stimulants such as Ritalin and Modafinil to treat the excessive sleepiness associated with the condition. These stimulants act as orexin agonists, and have had much success in treating the sleepiness, cataplexy and lapses into daytime sleep that the condition causes, and the success suggests that narcolepsy does have a cause related to orexin deficiencies. 

The identification of a possible chromosome mutation responsible for narcolepsy does not necessarily mean that genes are a definite cause, as it is possible that environmental triggers can play a role. It is more likely that the condition can be explained through a diathesis-stress hypothesis, with a genetic basis requiring specific environmental stressors to be present in order to result in the condition, an interaction between the effects of both nature and nurture. Not all people with the 6th chromosomal mutation on the specific gene develop narcolepsy, while not all narcoleptics have this gene mutation - suggesting factors other than genetics are involved. It would be too reductionist to simplify the condition down to the presence of one gene, ruling out environmental triggers such as stress or sleep deprivation or biological factors such as autoimmune malfunction.