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March 21, 2008

Page history last edited by PBworks 16 years, 2 months ago


 

Reference(s):

  1. Main Reference: Droogleever Fortuyn, H. A., Swinkels, S., Buitelaar, J., Renier, W. O., Furer, J. W., Rijnders, C. A., et al. (2008). High Prevalence of Eating Disorders in Narcolepsy with Cataplexy: A Case-Control Study. Sleep, 31(3), 335-341.

 

Article(s):

  1. Droogleever Fortuyn High Prevalence of ED in Narcolepsy w_ Cataplexy.pdf

 

Discussion:

Thanks to Nick Bello for presenting this paper and the background science that explores the link between narcolepsy and eating disorders. Nick's presentation and our discussion focused on Narcolepsy as a syndrome; it's relationship with certain HLA haplotypes, suggesting an autoimmune etiology; the definition of cataplexy; features of case-control design and reasons for including two different control groups; the main findings of the paper; possible etiopathologic links between sleep and eating behavior:

 

  1. Narcolepsy is a syndrome of disordered sleep in which patients experience abnormal urges to sleep and have an increase in the number of sleep cycles on polysomnogram. Nick reviewed briefly what normal sleep architecture looks like, and noted that patients with narcolepsy experience sleep-onset REM during the multiple sleep latency test (MSLT). Other symptoms present in narcolepsy include hypnagogic and hypnapompic hallucinations, sleep paralysis, and cataplexy. For further information, see the NINDS narcolepsy page, or Stanford's Center for Narcolepsy web pages.
  2. Cataplexy is the sudden loss of voluntary muscle tone. It is often brought on by states of emotional or physical arousal. Not everyone with narcolepsy has cataplexy, but those who do have among the strongest associations with HLA-DQB1*0602, which suggests that narcolepsy for many people may have an autoimmune cause. All the patients in the current study were HLA-DQB1*0602-positive.
  3. It is important in a case-control design that the controls have been chosen properly. The first control group was a group of age- and sex-matched controls chosen at random from a population-based sample used as controls in another study. Using this group allowed the authors to establish that rates of eating disorders were higher in their narcolepsy clinic than in the general population; however, because narcolepsy is associated with overweight, and because overweight is associated with eating disorders, the authors obtained a second group of controls that were age-, sex-, and BMI-matched, in order to control for the effects of BMI on frequency of eating behaviors.
  4. The authors found that rates of ED (mostly EDNOS) in their narcolepsy clinics was higher compared to the general population, and that even controlling for BMI, rates were higher, suggesting an effect of the diagnosis of narcolepsy on the rates of eating disorders above and beyond the effect of narcolepsy on weight.
  5. The above is fascinating because patients with narcolepsy have low CSF levels of orexin, a compound simultaneously discovered by groups interested in eating (they called it orexin because it is orexigenic, or stimulates eating) and groups interested in sleep (they called it hypocretin, because of homology with secretin and its being produced in the hypothalamus). The problem is that, as noted here, narcolepsy patients have low levels of orexin, but tend to overeat or binge, which would suggest that they have high levels of this orexigenic hormone. The authors speculate that the relationship between narcolepsy, orexin, and eating disorders might be mediated by melanocortin 4 receptors, which have been associated with binge eating and are located on cells in the arcuate nucleus of the hypothalamus. Clearly more needs to be worked out!

 

These words arrived from our sleep expert, David Neubauer, who was not able to make it to the meeting:

Exactly how orexin (also called hypocretin) is associated with sleep and feeding remains to be elucidated, but clearly there are important roles.

Orexin is very low in narcolepsy with cataplexy patients, who, by definition, are excessively sleepy. There's still no direct way to increase their orexin levels in the hypothalamus. However, the discovery of the narcolepsy association has led some pharmaceutical companies to explore whether decreasing orexin could benefit insomnia patients. A Swiss company has been very active in this area and hopes to market an orexin antagonist within a few years. I wonder how that would influence eating behavior.

 

Hopefully David will be able to join us for another meeting....

 

 

Thanks for coming to this meeting. The next journal club will take place on APRIL 4 at NOON. As always, PLEASE let me know if there are topics/areas you are interested in, and we will work on getting them included.

 

 

Graham

 

 

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