By Rich Van Konynenburg, Ph.D.
Gail Adler, M.D., Ph.D. is an Associate Physician at Brigham and Women's Hospital and an Assistant Professor of Medicine at Harvard Medical School, both in Boston. She is an endocrinologist and has performed research on the factors regulating secretion of cortisol and aldosterone, and how these are involved in disease states. She has also studied the interactions between the hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system.
Gail spoke at the NIH CFS Workshop on June 12, 2003, about the HPA axis and the autonomic nervous system in fibromyalgia (FM), and in particular about a study to see if there are differences in the circadian pacemaker (biological clock) operation between FM patients and healthy normal controls.
Before discussing her talk, I want to give some background information: In a normal human the daily circadian ("about a day") rhythm is set by a pacemaker that is located in the suprachiasmic nuclei (SCN), which are part of the hypothalamus in the brain. In the absence of synchronizing input, this pacemaker would establish a natural rhythm with a period slightly longer than 24 hours. This is called the endogenous circadian rhythm. In a normal person, this endogenous rhythm is entrained to the 24-hour day-night cycle established by the sun by means of special photoreceptors in the retinas of the eyes, which send signals to the SCN. If a person flies to a different time zone, it takes a while for the endogenous rhythm to be entrained to the new day-night cycle, and this is called jet lag. Some blind people lose their synchronizing signal, while others, who still have these special photoreceptors operating, remain synchronized to the day-night cycle.
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The circadian rhythm controls several cycles in the human body: the sleep-wake cycle via melatonin secretion from the pineal gland, the cortisol secretion cycle by the adrenals via control of ACTH secretion from the pituitary gland, and the core body temperature cycle, regulated by the hypothalamus. Growth hormone secretion by the pituitary is linked to stage 4 sleep, which in turn is linked to the sleep-wake cycle.
Disruption of the normal synchronization of the circadian rhythm with the sleep-wake cycle (as can occur in shift work) or with the day-night cycle (as in jet lag) is known to produce many of the same symptoms that are found in FM and CFS, including difficulty sleeping, fatigue, malaise, pain in the muscles, problems with the digestive system, and decreased cognitive function. This has prompted researchers to look into the circadian rhythm in these disorders, and the work that Gail described was a study of the endogenous circadian rhythm in FM.
The goal of this study was to remove the entrainment signals and allow the endogenous circadian rhythm to run free, comparing its behavior in PWFs [persons with fibromyalgia] and normal, healthy people. She and her group studied premenopausal women, placing them on 40 hours of what is called a constant routine. This amounts to constant enforced wakefulness, constant posture, hourly small meals, controlled activity and very low light levels (doesn't that sound like fun?) They measured the core body temperature and blood levels of melatonin and cortisol over time. They found that there was no significant difference between the women with FM and the control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, or core body temperature. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with FM compared with healthy women, there were no circadian rhythms in either parameter. The conclusion of the researchers was that abnormalities in circadian rhythmicity are not a primary cause of FM or its symptoms.
In one of her published papers, Gail and coworkers noted that "Studies suggest that there may be lower activity of a number of hypothalamus-pituitary-peripheral gland axes and altered autonomic nervous system function in patients with FM. These reductions in activity are mild to moderate and do not result from alterations in circadian rhythms. The reduced hormonal and autonomic responses appear to reflect an impairment in the hypothalamic or central nervous system response to stimuli rather than a primary defect at the level of the pituitary gland or the peripheral glands."
I think that these results are consistent with some type of damage process that takes place in the hypothalamus or in parts of the brain that feed signals to the hypothalamus. At this point, I don't think anyone knows what this damage process is.