Introduction
Scientific Overview
Stress and Stress Tolerance
HPA Axis
Circadian Rhythms
Immune System
Placebo Effect
Burnout
Chronic Fatigue Syndrome
Chronic Pain
Psychiatric vs Organic Debate
Irritable Bowel Syndrome
Chronic Lyme Disease
Recovery from CFS
Resources
Search Site
Contact

NOTE: for a scientific overview of the theory, see the persistent burnout theory of CFS.

Chronic Fatigue Syndrome (CFS)

Chronic Fatigue Syndrome (CFS, also known as myalgic encephalomyelitis or ME), is a severe, debilitating condition consisting of a number of different physical, physiological, neurological and psychiatric symptoms including:

Not all patients suffer from all of the symptoms, and there are many other symptoms that are also present in some patients. The only symptom that must be present for a diagnosis of CFS to be made is severe, disabling fatigue for a period of over six months. Other symptoms will occur in most cases, but are not required for a diagnosis under the Oxford criteria (although the CDC criteria does require at least four other symptoms out of a list to be present). There is no definitive test for CFS, so it is essentially an exclusion diagnosis that is reached when all other causes of illness have been ruled out. (As of 2015 there is potential for the repeat cardiopulmonary exercise test to be used to diagnose CFS, but more research is needed to verify this test).

Sometimes muscle pain is listed as a symptom. However if the pain is widespread it may result in a diagnosis of fibromyalgia rather than CFS. The symptoms of fibromyalgia are very similar to CFS, the difference being that with fibromyalgia the main symptom is widespread chronic musculoskeletal pain. There is, however, a broad overlap between CFS and fibromyalgia, with many patients suffering from symptoms of both conditions, and it is possible that both CFS and fibromyalgia are caused by the same underlying illness mechanism.

There is also a spectrum in severity of symptoms, with many patients suffering from what could best be described as mild burnout or chronic fatigue, without being ill enough to be classified as having CFS. Many people suffer from symptoms such as being tired all the time, unexplained weight gain or susceptibility to infections. While some people would like to classify these patients as having a different (and less important) illness than CFS, this does not reduce the impact that these symptoms have on the lives of the people suffering from them.

In the UK CFS used to be known as myalgic encephalomyelitis (ME), as it was originally thought to be caused by inflammation of the brain and spinal cord due to a viral infection. Encephalomyelitis can occur after infection by a number of viruses and bacteria, such as measles, herpes simplex, human herpesvirus 6 (HHV-6) and Epstein-Barr virus. However the inflammation in ME was always just presumed to occur, according to Donald Acheson who originally coined the term ME. Research since then has failed to find encephalomyelitis, and the term ME has largely been abandoned by researched in favour of CFS. The term ME, however, remains popular among patients who feel that the name CFS trivialises their illness.

There is much debate about whether CFS is a "real illness", whether it is caused by a virus, and whether it is just psychological (or "all in the head"). Anyone who takes even the most cursory glance at the recent scientific evidence can clearly see that CFS is most definitely a real condition, and not purely an imaginary illness. This evidence includes CAT scans showing significantly shrunken adrenal glands in a subset of patients, as well as various physiological abnormalities.

As for the symptoms of CFS, there is a wide overlap with a number of other conditions such as burnout, fibromyalgia, atypical depression, panic-anxiety disorder, irritable bowel syndrome and dysthymia.

Dysthymia is a form of long-term depression lasting more than two years, which also includes symptoms such as poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or indecisiveness, and feelings of hopelessness. Many CFS patients suffer from most or all of the symptoms of dysthymia.

Atypical depression is a type of major depression that includes symptoms such as marked fatigue/weakness, excessive sleepiness, weight gain, and moods that strongly vary based on circumstances. As well as sharing similar symptoms to CFS, atypical depression is also associated with a reduced HPA axis drive similar to CFS.

For further discussion on the psychiatric versus organic debate about the illness, see:

Psychiatric vs Organic Debate

Mechanism for CFS

Both CFS and burnout are associated with an underactive HPA axis, the body's main stress regulation system. This hypofunction of the HPA axis is also seen in long-term chronic stress, PTSD, as well as after the cessation of a period of long-term stress. It is unlikely that there is any actual damage to the HPA axis. Rather, it is likely to be an imbalance in the neurons and receptors in the hypothalamus, prefrontal cortex and other brain structures which control the HPA axis, in the same way that major depression is thought to be caused by an imbalance of serotonin and noradrenaline neurons and receptors. The changes that occur in the hypothalamus and other brain structures during CFS may be protection mechanisms that prevent the body from undertaking stressful activities that appear not to be beneficial.

With CFS, the initial trigger is usually a viral infection, environmental toxin or emotional stress—all of which are known to activate the HPA axis—or a combination of such stressors. Due to factors such as personality, genetics and mental attitude, this initial trigger then leads to a prolonged imbalance in HPA axis function in some patients, resulting in CFS. This is summarised below:

This is in contrast to the simplistic psychiatric model for CFS, which goes something along the following lines:

Although there is no direct conscious control over the hypothalamus or the HPA axis, there are many pathways from the cerebral cortex to the hypothalamus that could cause the disturbance in HPA axis function seen in CFS patients. One possible candidate is the prefrontal cortex (PFC). The PFC is an involved in planning long-term goals, and is an important negative-feedback regulator of the HPA axis. Studies on mice have shown that the forebrain (which includes PFC, hippocampus, and basolateral amygdala) regulates the stress response to psychogenic stressors, reducing the HPA axis response through negative feedback. Interestingly, this negative feedback only seems to apply to psychogenic stressors, not physiological stressors.

A number of studies have shown that CFS patients have reduced grey matter volume in the lateral PFC, and one study has shown that this reduction is reversed after treatment with CBT. It may be that in CFS the PFC gets stuck in a negative feedback loop, resulting in the continued suppression of the HPA axis even after the initial stressor has been removed.

Fries et al hypothesize that the hypocortisolism seen in stress-related disorders such as CFS, burnout and PTSD is actually a protective mechanism which has evolved to conserve energy during threats that are beyond the organism's ability to cope. CFS may be a maladaptive burnout state resulting from this protective mechanism.

Gupta et al developed a model of the HPA axis, and found that in certain situations it could get stuck in a low-cortisol state which corresponded to the HPA axis abnormalities seen in CFS patients. A follow-up report by Ben-Zvi et al hypothesized that the HPA axis could possibly be corrected by suppressing cortisol for a time, until the HPA axis naturally moves into its normal steady state. However they say that the model of the HPA axis is incomplete, and that further research is necessary to fully understand the dynamics of the HPA axis.

Brain vs HPA axis in causing CFS

Although the HPA axis has been shown to be dysfunctional in CFS, it is unclear exactly how central this is to CFS. In many CFS patients cortisol has been shown to be normal, and the HPA axis only shows abnormal function during stress tests. Even then, the reduction in cortisol does not appear to be sufficient to cause the severity of the fatigue seem in CFS.

As discussed in the burnout section, the brain has a number of areas dedicated to assessing the costs vs benefits of stressful activities, as well as a "central governor" which generates the feeling of fatigue. The "central governor" directly controls the motor cortex, which could be what causes the fatigue in CFS (and would also explain symptoms such as paralysis, weakness and numbness which are sometimes associated with CFS). These areas of the brain are also important regulators of the HPA axis, which may contribute to some of the fatigue experienced in CFS, especially during exercise (where cortisol is important for maintaining a high level of energy output).

Autonomic Nervous System

Many CFS patients suffer from a dysregulated autonomic nervous system (ANS), with symptoms such as dizziness, tachycardia, anxiety, reduced gut motility and impaired stomach emptying. Research by Tanaka et al. shows that CFS patients tend to have decreased parasympathetic nervous system function, along with a corresponding compensatory increase in sympathetic nervous system function. This parasympathetic-to-sympathetic shift also happens in healthy controls who are suffering from acute fatigue.

Research shows that the autonomic nervous system and HPA axis are closely linked, and that activation of one system causes a corresponding activation of the other. It is likely that the same part of the brain which is suppressing the HPA axis is also suppressing the parasympathetic nervous system, and the sympathetic nervous system has to compensate when the person tries to push through the fatigue, resulting in symptoms such as tachycardia and anxiety.

Recovery from CFS

See also Recovery from CFS/ME/Burnout

In terms of recovery, there is very little research to suggest what actually cures CFS, or that there are any effective cures at all. In most cases the illness simply goes away by itself after a period of time, which can be anywhere from a few months to over 10 years.

There is not much research on the exact percentage of patients who recover from CFS. The main problem is the definition of what recovery actually is. Many patients do recover somewhat, but most of them continue to have some symptoms.

One study gives a figure of 12% for total recovery, while others give figures of between 30% and 60% for improvement and 2% for complete resolution of symptoms. Anecdotal evidence suggests that the majority of patients do recover fully (although exactly what percentage is unclear).

Research shows that an important factor in recovery is the duration of symptoms, with patients who have had the illness for a shorter period of time being more likely to recover at some point in the future. A number of studies have shown that the chances of recovery are greatly reduced if the symptoms have persisted for longer than two years. Some patients recover within six months to a year, while others have had the illness for over 10 years with no sign of a resolution, although the severity of the illness tends to vary over time.

One study reports that 46% of CFS patients showed spontaneous improvement after a period of one year, even though no treatment was used during that one-year period. This study found that complete recovery only occurred when the symptoms had lasted for less than 15 months.

Other factors that have been shown to reduce the chances of recovery include older age, as well as current and lifetime history of dysthymia.

CBT and GET

Recovery from CFS, when it does occur, is generally long-term and gradual. Currently the only treatments for CFS that have been proven to work are cognitive behavioural therapy (CBT)—which addresses psychological attitudes to the illness—and graded exercise therapy—which aims to gradually increase physical activity. However, even these treatments do not help everyone who has CFS, and they tend to be not much better than simply doing nothing at all. Research has shown that adding cognitive elements to a treatment does not make it more effective, and that recovery is not associated with an increase in activity, which calls into question the theories behind CBT and GET.

Long-term follow up studies of CBT and GET all tend to show that while CBT and GET do result in short-term improvement over "usual care", in the long-term the CBT and GET patients don't maintain any significant improvement compared to patients receiving usual care. However this isn't because the benefits of CBT and GET are lost, it is because untreated patients eventually (and gradually) improve. So it seems that CBT and GET result in patients improving more quickly.

Some CFS patients do have unresolved traumas, which CBT can help with. There are also some patients who do cling to abnormal beliefs about their illness, who might be helped with CBT. (Although that is true for all illnesses, and it doesn't really explain the etiology of CFS). CBT may also help patients get out of the negative attitude to the illness itself, which may contribute to symptoms. However, the incomplete theory behind CBT when used to treat CFS puts off a lot of patients, and the reason that CFS works could be something of a placebo, due to the fact that it increases motivation and self-efficacy, and gives patients a positive mindset.

Anecdotal reports of people who have recovered suggest that psychological factors such as self-efficacy, motivation, goals and mental attitude play a significant role in recovery. These are the same factors that are important in determining whether or not someone suffers from burnout during a period of chronic stress.

Reports of Recovery from CFS

There are regular reports of people recovering from CFS published in newspapers and health magazines. The reports of patients themselves are a valuable source of information about the illness, and give an indication of what factors are important in recovery. Obviously caution needs to be exercised when analyzing anecdotal reports, but they can still point towards what might work to treat CFS.

The treatments generally fall into two categories: an alternative therapy which probably relies on the placebo effect, or a change in lifestyle. No matter what type of treatment or therapy is used, in all cases there is an increase in positive goals, motivation and attitude, and it is likely that it is this change that results in a recovery from CFS by normalising the functioning of the HPA axis and related systems. For more details on exactly how an increase in goals and movitation can result in physiological changes and a recovery from CFS, see the Persistent Burnout Theory.

It should be noted that I do not recommend or endorse any of the alternative therapies discussed in these reports. Such treatments are likely to be expensive and potentially dangerous, and many owe their benefit purely to the placebo effect.

It should also be noted that not all alternative treatments are purely placebo, just as some conventional drugs have been shown to be no better than placebo. For a further discussion see the placebo effcect page. However in the end, no alternative treatment—nor any treatment with conventional drugs— will likely do anything other than provide temporary, palliative relief for some of the symptoms of CFS. Permanent recovery is only likely to happen when the patient addresses the factors causing the illness

Alex Howard

"At the age of sixteen years old Alex Howard was left virtually bed-bound and hardly able to walk by a severe chronic illness, which according to the medical profession there is no cure for. After two years of severe chronic illness and developing clinical depression and near suicide, Alex made a life-changing commitment: he would do everything he possibly could to transform himself and his surroundings.

Alex spent virtually every minute of the next five years searching in the fields of psychology, neuro-linguistic programming, life coaching, spirituality, hypnotherapy, personal development, nutrition, meditation and studies of consciousness, yoga and healing, and was eventually able to return himself to health and happiness, along with creating a whole new life for himself."

"Karen", from an article published in issue 27 of "Healthy Way" magazine:

"Karen was diagnosed with ME and for three years it was particularly severe, which left her feeling totally exhausted physically and mentally. Karen was so ill that for two years she was largely confined to bed. However, since having Kinesiology sessions, she has made a good recovery".

The article goes on to say that she is now able to go out of the house on a daily basis, whereas previously she had been confined to bed. She used to feel totally exhausted after walking 5 minutes, but can now walk for 1.5 hours. Her head used to feel "fuzzy", and she had difficulty concentrating, but now she can focus much better.

Karen says that during her Kinesiology sessions it became apparent that she had multiple sensitivities to everyday things such as dust, wheat, etc., and that she had high levels of mercury in her system. She also thinks that she was sensitive to electromagnetic radiation from household appliances.

Kate Lock, from an article published in the Times Saturday Magazine

Two years ago Kate Lock, an author, suffered from intense fatigue, and didn't have the energy to take her daughter to school. She was so tired that she slept all afternoon. She had a succession of illnesses, and her glands were swollen for months. She also had a "fuzzy" brain, and couldn't write more than a paragraph. Her other symptoms included digestive problems, bloating, depression and PMS. This was the latest in a cycle of health problems that had begun in her twenties.

After learning about candida, Kate thought that her health problems might be due to candida infection. After starting an anti-candida diet, Kate noticed a significant improvement in her health within one or two weeks. After being on the diet for six months she felt that she was 70% better, and her symptoms such as thrush, migraines, PMT, joint pains, fatigue and concentration problems had all disappeared.

Anna Selby, from an article published in the Times Saturday Magazine:

Anna began to have the symptoms of ME when she was in science college at 16. Her symptoms included weight gain, low energy levels (she was sleeping most of the day and going to college for an hour a day), and intense sweating. One day she came out in a rash, and her symptoms became so severe that she was confined to bed for eight months.

Eventually her family found a doctor who knew about ME, and he suggested that she should go somewhere that meant a lot to her. The family decided to go on holiday to Cardigan Bay, where she had seen her first dolphin when she was four years old.

The article discusses how Anna began to recover from ME, and how she went back to see the dolphins when she had a relapse. She has now fully recovered, and works for the Biscay Dolphin Research Program. The article talks about the therapeutic effects of dolphins, and about cases of people being cured from anorexia, depression and other illnesses through contact with them.

Clare Kerr, from an article published in the Sunday Times:

Clare's symptoms began when she was 17, after a bout of glandular fever. After spending three months recovering from the illness, she was glad to get back to school. As she had been away for so long, she had to catch up on the previous term's work, which meant staying up late to write essays and not getting much sleep.

Six weeks into the term, one morning she woke up and could barely move. The article doesn't give much detail about her symptoms, but they included severe exhaustion, tunnel vision, pounding headache and auditory hypersensitivity. Her doctor didn't believe in post-viral fatigue, and eventually she was taken to St Bart's hospital where she was referred to a psychiatrist. She didn't understand what was happening, as she was sure that there was nothing wrong with her mentally.

For the next five years she tried a number of alternative therapies, but nothing seemed to work. Eventually she was referred to the Breakspear hospital, which has a history of treating patients with ME using various alternative therapies.

She was diagnosed with a number of vitamin and mineral deficiencies, and was told she had allergies to a number of foods and chemicals. She was also told that her EBV infection (causing the glandular fever) was due to her having a low immune response.

She has now changed her diet in order to avoid the foods that she is "allergic" to, and also takes a number of vitamin and mineral supplements to correct the supposed deficiencies. She also practises yoga and meditation, doesn't smoke or drink, and generally tries to have a healthy lifestyle. Since starting this regime, her health has improved immensely. The article doesn't give too much detail, but the impression given is that her health is now pretty much normal, and she can now live a normal life.

Other reports of patients who have recovered from CFS:

Guardian article about a bed-bound patient who gradually recovered using CBT and GET
Patient who recovered from long-term severe ME
CFS patient who recovered after being put on a management programme by a sympathetic doctor
CFS/FMS patient who recovered after going on an antiviral drug
CFS patient who recovered after following the NAET treatment programme
CFS patient who recovered after following the anti-Candida diet, but later relapsed
CFS/FMS patient who recovered using supplements of sodium, potassium, magnesium and calcium
Bruce Campbell — has been fully recovered from CFS for over a decade, and created a self-help programme.
Dan Neuffer — set up a training programme after recovering from CFS.
Ashok Gupta — created the "Gupta amygdala retraining" programme after recovering from CFS.
Toby Morrison — created a recovery programme after recovering from CFS.
Ken Lassesen — has suffered 3 episodes of CFS over a period of 40 years due to stress, and has recovered each time with the help of antibiotics and probiotics.
Jessica Taylor — suffered from severe CFS and was fed through a tube for 2 years and couldn't speak for 18 months. Although not fully recovered, she is now able to walk, talk, and is getting married, with help from CBT and exercise therapy at the Burrswood hospital.
Shelley Gawith — Recovered from being bedridden with severe CFS after working in a stressful accounting job. She recovered after quitting her stressful job, being nursed back to health by her parents, and changing her diet.
Juliet Preston — recovered after taking supplements, off-label medications, and doing yoga, walking and mental activities.

Sarah Beilfuss, who recovered after being mostly bed-bound for a year:

Treatment of CFS

There is a tendency for both patients and doctors to concentrate on treating the symptoms of CFS rather than trying to cure the illness itself. Many patients take various herbs and supplements in order to cure their symptoms. In most cases these supplements have been shown to have no effect whatsoever, and at best they only give a mild improvement.

CFS researchers sometimes give antiviral treatments to patients who have persistent herpes infections such as EBV. These treatments, while they may help in combating any viral infections, has not been shown to actually cure CFS itself. Quite a few clinical trials have been published by Straus, Lerner, Montoya and others, and all of them have shown that antiviral treatments have no significant effect on the symptoms of CFS.

When hormone tests are performed on CFS patients by some doctors, there is a tendency to treat the illness by replacing deficient hormones, such as testosterone, cortisol, growth hormone or the thyroid hormones. Again, this only cures some of the symptoms and does not provide a cure for CFS.

Many CFS patients use sleeping pills to cure insomnia, but in many cases this simply leads to a dependence on the medication and only offers a partial or temporary cure for the actual insomnia. This is also the case for treatments for other symptoms of CFS, such as depression, anxiety and tachycardia. In some cases the patient ends up taking a large number of different drugs and supplements, and may end up feeling just as bad or worse than if they were taking nothing!

Studies have shown that providing cortisol replacement therapy in CFS patients gives a small improvement in symptoms, but does not cure the illness and is generally not recommended. The problem with cortisol replacement is that it tends to suppress the HPA axis responsiveness of the patient, resulting in adrenal insufficiency after the treatment has ceased. In addition, as it only replaces one hormone it is not surprising that it does not cure all of the symptoms.

The existing CFS treatments really just seem to be skirting about the main issue of trying to restore the normal HPA axis activation / brain function. What is likely to be more effective is to develop a treatment which combines certain aspects of existing treatments such as CBT and graded exercise, and which also attempts to make patients aware of the causes of the illness and the steps that they can take in order to cure themselves.

CBT, although useful, is based on the notion that patients' negative beliefs about their illness serve to perpetuate the illness, through negative feedback. While this may be a factor with some patients, it doesn't fully explain the etiology of the illness, and as discussed earlier research shows that adding cognitive elements to a treatment does not make it more effective. While CBT does help somewhat, it is possible that it is due to something along the lines of the placebo effect, and not for the reasons given by the practitioners. Many CFS patients will not have anything to do with CBT because it implies that they are deliberately prolonging their illness.

The treatments that tend to work best for curing CFS can be divided into three categories: psychological, changes in lifestyle and the placebo effect. All three types of treatment ultimately work in the same way, with the psychology of the patient determining the effectiveness of any particular treatment. In many cases it is probably the act of doing the treatment that results in recovery, rather than any actual benefit from the treatment itself. Purely psychological treatments, such as CBT and counselling, tend not be very effective, as they tend to focus on areas such as emotional problems which are not necessarily a significant factor in many cases. In the lifestyle category, many patients find that getting a new job or changing their career to something that they really enjoy results in curing their CFS symptoms. In terms of the placebo effect, many dubious alternative therapies that rely on the placebo effect for their effectiveness have resulted in people completely recovering from CFS. Treatments that have worked include anti-candida diets, kinesiology, food intolerance diets, as well as many others. It should be pointed out that these were not patients who had mild symptoms; many of these people were bed-ridden and had highly debilitating physical and mental symptoms, all of which were completely cured by apparently trivial treatments.

Perhaps the most beneficial way of treating CFS would be a combination of psychological/lifestyle and pharmacological treatments. Initially, the patient could be treated with drugs to help cure symptoms such as adrenal insufficiency, depression, anxiety and insomnia. This would provide a temporary cure for some of the symptoms, which would then allow the patient to work on the long-term recovery process. Factors that are likely to be important in this healing process might include:

The concept of flow developed by Mihaly Csikszentmihalyi closely corresponds with the factors that result in recovery from CFS. Flow is the mental state of being fully immersed and enjoying an activity, with a feeling of being energized. It is similar to being "in the zone", and is similar to Zen Buddhism. Studies of workers suffering from burnout have shown that the absorption and enjoyment aspects of flow are associated with energy after work, and that a harmonious passion for work results in low levels of burnout.

What is important is to make changes in mental attitude and/or lifestyle that break the vicious circle of HPA axis suppression leading to illness, which then leads to further suppression of the HPA axis.

Patient support groups are not always useful for CFS patients. In many cases these groups foster the myth that recovery is not possible, which may in itself be detrimental to the chances of recovery.

In summary, the only real way to treat CFS is to get to the heart of the illness and treat the underlying factors that cause the various mental, physical, endocrine and immune system symptoms associated with the illness. Concentrating on just one single group of symptoms will only bring partial relief, and will simply serve to prolong the illness. Recovery is not instant, and may take many months due to long-term changes that have occurred in the HPA axis, the brain, and associated areas which may take a long time to reverse. However, recovery is possible, even for the most severely disabled patients.

See also the CFS recovery section.


References and external links

Wikipedia entry on CFS

Furay, A. R., Bruestle, A. E., & Herman, J. P. (2008). The role of the forebrain glucocorticoid receptor in acute and chronic stress. Endocrinology, 149(11), 5482-5490.

Soto NE, Straus SE, "Chronic Fatigue Syndrome and Herpesvirus: the Fading Evidence", Herpes 2000 May;7(2)46-50

White C, Schweitzer R, "The role of personality in the development and perpetuation of chronic fatigue syndrome", J Psychosom Res 2000 Jun;48(6):515-24

Creswell C, Chalder T, "Defensive coping styles in chronic fatigue syndrome", J Psychosom Res 2001 Oct;51(4):607-10

Kuratsune H, Yamaguti K, Lindh G, Evengard B, Hagberg G, Matsumura K, Iwase M, Onoe H, Takahashi M, Machii T, Kanakura Y, Kitani T, Langstrom B, Watanabe Y, "Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake in the brain", Neuroimage 2002 Nov;17(3):1256-65

Bombardier CH, Buchwald D, "Outcome and prognosis of patients with chronic fatigue vs chronic fatigue syndrome", Arch Intern Med 1995 Oct 23;155(19):2105-10

Pheley AM, Melby D, Schenck C, Mandel J, Peterson PK, "Can we predict recovery in chronic fatigue syndrome", Minn Med 1999 Nov;82(11):52-6

Clark MR, Katon W, Russo J, Kith P, Sintay M, Buchwald D, "Chronic fatigue: risk factors for symptom persistence in a 2 1/2 year follow-up study", Am J Med 1995 Feb;98(2):187-95

Deale A, Husain K, Chalder T, Wessely S, "Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study", Am J Psychiatry 2001 Dec;158(12):2038-42

Brunello N, Akiskal H, Boyer P, Gessa GL, Howland RH, Langer SZ, Mendlewicz J, Paes de Souza M, Placidi GF, Racagni G, Wessely S, "Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas", J Affect Disord 1999 Jan-Mar;52(1-3):275-90

Neeck G, Crofford LJ, "Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome", Rheum Dis Clin North Am 2000 Nov;26(4):989-1002

Scott LV, Teh J, Reznek R, Martin A, Sohaib A, Dinan TG, "Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study", Psychoneuroendocrinology 1999 Oct;24(7):759-68

MacHale SM, Cavanagh JT, Bennie J, Carroll S, Goodwin GM, Lawrie SM, "Diurnal variation of adrenocortical activity in chronic fatigue syndrome", Neurophychobiology 1998 Nov;38(4):213-7

Gaab J, Huster D, Peisen R, Engert V, Heitz V, Schad T, Schurmeyer TH, Ehlert U, "Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation", Psychosom Med 2002 Nov-Dec;64(6):951-62

Malouff, J. M., Thorsteinsson, E. B., Rooke, S. E., Bhullar, N., & Schutte, N. S. (2008). "Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis". Clinical psychology review, 28(5), 736-745.

Fries, E., Hesse, J., Hellhammer, J., & Hellhammer, D. H. (2005). "A new view on hypocortisolism." Psychoneuroendocrinology, 30(10), 1010-1016.

Miller, E. K., & Cohen, J. D. (2001). "An integrative theory of prefrontal cortex function". Annual review of neuroscience, 24(1), 167-202.

de Lange, F. P., Koers, A., Kalkman, J. S., Bleijenberg, G., Hagoort, P., van Der Meer, J. W., & Toni, I. (2008). "Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome". Brain, 131(8), 2172-2180.

Papadopoulos, Andrew S., and Anthony J. Cleare. "Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome." Nature Reviews Endocrinology 8.1 (2012): 22-32.

Gupta S, Aslakson E, Gurbaxani BM, Vernon SD (2007). "Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability." Theor Biol Med Model. 2007 Feb 14;4:8.

Amos Ben-Zvi, Suzanne D. Vernon, Gordon Broderick (2009). "Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction." PLoS Comput Biol. 2009 Jan; 5(1): e1000273.

Lavigne, Geneviève L., Jacques Forest, and Laurence Crevier-Braud. "Passion at work and burnout: A two-study test of the mediating role of flow experiences." European Journal of Work and Organizational Psychology 21.4 (2012): 518-546.

Demerouti, Evangelia, et al. "Work-related flow and energy at work and at home: A study on the role of daily recovery." Journal of Organizational Behavior 33.2 (2012): 276-295.

Tanaka, M., Tajima, S., Mizuno, K., Ishii, A., Konishi, Y., Miike, T., & Watanabe, Y. (2015). Frontier studies on fatigue, autonomic nerve dysfunction, and sleep-rhythm disorder. The Journal of Physiological Sciences, 65(6), 483-498.



Copyright (c) Mind-Body-Health.net, All Rights Reserved

DISCLAIMER: Mind-Body-Health.net is an educational resource for chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), burnout and related disorders, and is not giving medical advice. Seek advice from a medical practitioner before making any changes to your life, or if you experience worsening symptoms. CFS is a diagnosis of exclusion, so it is important to rule out other causes for illness.