Sleepiness in CFS and Fibromyalgia May Be a Form of Narcolepsy!

In our recent blog discussed how orexin(hypocretin) effects sleep patterns and may have an important role in CFS and sickness syndrome. A new study using a pharmaceutical called sodium oxybate showed significant improvement in patients in fatigue with both chronic fatigue syndrome and fibromyalgia and point to the "real possibility" that sleep problems in these conditions are similar to narcolepsy. In addition, the study suggests, even though further study is warranted that both CFS and FM are similar or not the same condition because of the improvements seen in patients with them.  We have noted similarities to sickness syndrome in these conditions and have emphasized that sickness syndrome also occurs in animals and importantly, narcolepsy also is not exclusive to humans and in often seen in dogs. Some breeds more commonly than others.

Other recent discoveries indicate that the major pathophysiology of human narcolepsy "is the loss of lateral hypothalamic neurons that produce the neuropeptide hypocretin (orexin). Approximately 90% of people diagnosed as having narcolepsy with cataplexy are hypocretin ligand deficient." Narcolepsy is thought to be an autoimmune related disorder and can alter regulation of cortisol and influence steroid production which also may initiate panic.  In our recent blog, we wrote how streptococcus pneumoniae may be an important trigger of orexin-influenced narcoleptic sleep behavior. This is important because this pathogen effects the severity of H1N1 and may mean that patients with EI may be more susceptible to both. Parkinsonism is also associated with alterations in hypocretin and future therapies in PD may involve treatments involving orexin. Some suggest that narcolepsy and Parkinson's disease have a common and therefore, one must begin to hypothesize that CFS and fibromyalgia may have the same or similar causal factors as PD and and narcolepsy.

For Further Reading About Orexins in CFS, Sickness Syndrome and Fibromyalgia, see

• How Changes in Neurons May Lead to Altered Cortisol in CFS/ME & Sickness Syndrome. HEIRS, January 1, 2010.
• Hormone Linked to Panic Attacks Also Linked to Endotoxin and Sickness Behavior

Spitzer, A. R. and Broadman, M. (2010). Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Practice, 10(1):54-59. http://www.citeulike.org/user/HEIRS/article/6512085
Zeitzera, J. M., Nishinob, S., and Mignotc, E. (2006). The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. Trends in Pharmacological Sciences, (27):368-374. http://www.citeulike.org/user/HEIRS/article/6512089
Thannickal, T. C., Lai, Y.-Y., and Siegel, J. M. (2007). Hypocretin (orexin) loss in parkinson's disease. Medscape Today. http://www.citeulike.org/user/HEIRS/article/6512132

How Changes in Neurons May Lead to Altered Cortisol in CFS/ME & Sickness Syndrome.

Background: Many research experts believe that endotoxin is a causal factor in the development of chronic fatigue syndrome. (Maes) In addition and as we have discussed on this blog, many of the symptoms may be attributed to sickness behavior or sickness syndrome. Generally, this is regarded as a reflection of immune responses that alter normal functions of hormones, neurotransmitters, etc. resulting in changes in behavior in humans and other animals.

We recently discussed how dysregulation of the hormone, ghrelin, may effect sickness behavior. A study just published provides more details about how another hormone may contribute to sickness syndrome and related alterations in behavior. According to the study, LPS endotoxin suppresses the neuronal circuitry in orexin and histamine neurons. As the abstract describes, the orexin neurons in the brain are important for behaviors including waking, feeding and reward-related behaviors and can be regulated by dopamine (Bubser), provide antinociceptive protection (Mobarakeh) and may reduce gastrointestinal injury through several mechanisms including injury from TLR signaling. In other blogs, we describe in detail how LPS from gram-negative bacteria and other environmental contaminants such as ozone can initiate inflammatory effects through TLR signaling and that genetic or environmental dysruption of the Nrf2 system will enhance the inflammatory effects.

Outside the brain, orexin neurons stimulate the production of cortisol in the adrenal glands and another studies shows orexin can time-dependantly raise cortisol levels as well as, influence steroidogenesis. Orexin studies have also revealed it regulates histamine release in the brain. Interestingly, narcolepsy which is suspected to be an autoimmune-related condition is associated with orexin deficiency. Aran proposes that streptococcus is an environmental trigger of narcolepsy. For this reason, the results of these studies in combination suggest that both gram-negative and gram-positive bacteria may contribute to sickness syndrome by altering orexin levels. In addition, orexin is a sexually-dimorphically expressed hormone which may help to explain the gender differences in the rates of environmental illness. (Johren)

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Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI

Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI: "URL: Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI

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Chronic stress is associated with high cortisol levels and emotional coping mechanisms in amnestic mild cognitive impairment.

Souza-Talarico, J. N., Chavesa, E. C., Nitrini, R., and Caramellic, P. (2009). Chronic stress is associated with high cortisol levels and emotional coping mechanisms in amnestic mild cognitive impairment. 28(5):465-470. http://www.citeulike.org/user/HEIRS/article/6197689

Low waking and Secretion of Cortisol Associated with the Presence and Genesis of Fatigue.

New study shows that low salivary waking cortisol and flat slope of diurnal secretion associated with fatigue. Cortisol is associated with future fatigue and cortisol secretion occurs early in the genesis of fatigue.

Kumaria, M., Badrick, E., Chandola, T., Adam, E. K., Stafford, M., Marmot, M. G., Kirschbaum, C., and Kivimaki, M. (2009). Cortisol secretion and fatigue: Associations in a community based cohort. Psychoneuroendocrinology, 34(10):1476-1485. http://www.citeulike.org/user/HEIRS/article/5951174

High Fat Diet Alters Testosterone and Cortisol Levels in Healthy Volunteers.

Title: Effect of meal fat content on salivary testosterone and cortisol levels in healthy female volunteers.

Summary: "indicate that the amount of fat consumed in a meal, can influence postprandial levels of salivary testosterone and cortisol and their circadian rhythm profile. Such an effect on steroid hormones might have an impact on the person’s daily activities and general health and wellbeing."



Citations: Al-Dujaili, E. A. S. and Bryant, M. L. (2005). Effect of meal fat content on salivary testosterone and cortisol levels in healthy female volunteers. http://www.citeulike.org/user/HEIRS/article/5927406

HPA Dysregulation Negatively Influences Cognitive Function in the Elderly.

Title: HPA Dysregulation Negatively Influences Cognitive Function in the Elderly.

Summary:  HPA axis dysregulation seems to be associated with low cognitive performance in the elderly. Slower cortisol elimination rates could predict cognitive decline affecting principally non-verbal functioning in men and verbal functioning in women. Interventions blocking this pathway may provide new therapies for blocking cognitive decline.

Citation: Beluche, I., Carrière, I., Ritchie, K., and Ancelin, M. L. (2009). A prospective study of diurnal cortisol and cognitive function in community-dwelling elderly people. Psychological medicine, pages 1-11. http://www.citeulike.org/user/HEIRS/article/5926636

Ptsd is associated with an excess of inflammatory immune activities

Gill writes, high lelels of inflammatory cytokines have been linked to PTSD vulnerability in trauma victims which the evidence suggests may be due to dysregulation of cortisol. The inflammatory decline may be responsible for health decline in patients with PTSD and treating the PTSD may decrease the risk for further negative health-related consequences. For more see the citation below.






Gill, J. M., Saligan, L., Woods, S., and Page, G. (2009). Ptsd is associated with an excess of inflammatory immune activities. Perspectives in Psychiatric Care, 45(4):262-277. http://www.citeulike.org/group/6880/article/5843242

Gene–environment interactions predict cortisol responses after acute stress: Implications for the etiology of depression

Gene–environment interactions predict cortisol responses after acute stress: Implications for the etiology of depression