Understanding Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) has baffled scientists and doctors alike, for quite some time now. The syndrome had to be diagnosed by elimination of other neurological and psychological maladies rather than be recognized by its own unique symptoms. Typically, patients report feelings of listlessness (anergy), depression, joint and muscle pain and headaches. Another remarkable symptom of this syndrome is the development of severe exhaustion, post-exercise. It is easy enough to see that these symptoms overlap with several other known malaises. CFS affects 0.2-1% of the population in the US. Women are more susceptible to CFS but patients from all age groups have been reported as well.

Viral infections were thought to be the root cause of CFS, typically infection with the XMRV (Xenotropic Murine Related Retrovirus). However, this theory has been discarded owing to conclusive evidence that patient samples in this study were found to be contaminated. Also, absence of the virus in body fluids of patients with confirmed CFS has been reported.

Recent research actually indicates that CFS is a complex syndrome of the nervous as well as immune systems. Blood supply to the brain was found to be reduced in CFS patients when compared to that seen in normal people. Exposure to cadmium is a possible factor that may cause reduced blood flow to the brain seen in CFS patients. There are structural changes in the brain as well. CFS patients show reduced grey matter as well as white matter in occipital lobes. These structural deficits may result in abnormal visual processing as well as reduced eye-limb coordination.

Researchers from the Queen Elizabeth Hospital, Adelaide, have reported changes in the structure of the brain stem in CFS patients. Grey matter (cell bodies of neurons) is reduced in the brainstem of CFS patients and altered regulation of blood supply to various parts of the brain is also observed. Alterations in the functions of astrocytes are thought to cause these changes. Astrocytes are star-shaped cells in the brain which provide nutrients to neurons and also have a role to play in tissue repair following brain trauma. The study indicates defects in astrocytes as well as trauma to the brain stem can contribute to structural abnormalities in the brain that lead to the development of CFS.

Another model for understanding this complex disease suggests that a combination of immune factors such as increased levels of pro-inflammatory cytokines and changes in brain pathology may by jointly responsible for the development of CFS. This model can therefore accommodate the fact that CFS has been known to set in after patients have experienced a bout of infection from various known pathogens (apart from XMRV). This model suggests that infections could trigger a pro-inflammatory response as well as deplete antioxidants from the body. These changes may contribute to development of CFS.

Therapeutic approaches to CFS are limited. Supplementation with magnesium and zinc has been suggested if cadmium is detected in patients with CFS. Current therapies focus on providing relief from specific symptoms. Scientific evidence, however, indicates that an efficient therapeutic strategy can emerge only after the neuronal correlates of this disease are understood.


Barnden LR, Crouch B, Kwiatek R, Burnet R, Mernone A, Chryssidis S, Scroop G, & Del Fante P (2011). A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis. NMR in biomedicine, 24 (10), 1302-12 PMID: 21560176

Biswal B, Kunwar P, & Natelson BH (2011). Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling. Journal of the neurological sciences, 301 (1-2), 9-11 PMID: 21167506

Morris G, & Maes M (2012). A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome. Metabolic brain disease PMID: 22718491

Pacini S, Fiore MG, Magherini S, Morucci G, Branca JJ, Gulisano M, & Ruggiero M (2012). Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medical hypotheses, 79 (3), 403-7 PMID: 22795611

Puri BK, Jakeman PM, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH, Waldman AD, & Gishen P (2012). Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study. The British journal of radiology, 85 (1015) PMID: 22128128

Image via Adam Gregor / Shutterstock.

  • Tiffani Cappello

    I suffered CFIDS for many years and have since overcome it. Last summer I ran 20+ miles a week as a testimony to the fact that this illness can be overcome.

    I am firmly convinced that CFIDS is rooted in a complex interaction between psychological and physiological factors. It is the exhaustion stage of Hans Seyles GAS syndrome. Few therapies that do not address psychonueroimmunological factors are ever successful in bringing about long term recover for patients.

    • mary

      Hi Tiffani, it’s so nice to read about someone overcoming CFS and being to run! So, what did you do? How did you battle it away? When you got it, was it a sudden onset after a virus?? Any more info you could give me I would appreciate.
      Thank you. I’m happy for you.

      • Shirley

        I am sorry to tell you but there is not a ‘cure’ for CFS. CFS has a pattern of remission & relapse. If there was a cure, it would be docmented, tested & based on scientific results. Not just the say so of a person…how do you know that the person actually had CFS? A good place to find out about & get good information from is the CDC website. It writes about chronic infections, stress, immune dysfunction and nutritional deficiency. Also the release of cytokines, interferon- Alpha & Interleukin-6 which cause sleep problems, fatigue, metabolism & immune problems, as well as, changes in the secretion of the hormone cortisol. Hormone dysfnction has a huge impact on how the body maintains homeostasis or balance. There is a feedback system that is destroyed by the huge increase of cortisol in the body from stress, illnesses, infections, etc. Please read the info. from the CDC. I hope it helps.

  • Agatha Andrews

    Thanks for a generally informative piece about this disease. However, it is not in fact true that “listlessness and depression” are symptoms of this disease. Those would be symptoms of a coexisting depression, if the patient were also depressed. However, listlessness and depression are not themselves symptoms of CFS (now widely known as ME/CFS). Most people with CFS are anything but listless. In fact, we are trapped inside of extreme fatigue or hamstrung by the severe reactions we get to exertion. If a ME/CFS patient is not clinically depressed, which most are not, we are actually frustrated and chomping at the bit to be able to be more active. The major diagnostic symptoms are: 1) post-exertional reactions (flu-like exhaustion for days, weeks, or even months in response to a minor increase in activity); 2) extreme fatigue that is unrelieved by sleep; 3) disordered sleep; 4) joint, muscle, and neuropathic pain; 5) cognitive deficits, especially when overexerting. Some patients also have overactive or underactive immune responses, orthostatic intolerance (reactions to standing or sitting upright), and other symptoms.

  • Victoria

    You may want to look at the web site of the National CFIDS Foundation that just announced a cause accompanied by a dozen references! People who think they may have “had” this illness are probably confused by the name which is but one symptom.


  • Valentijn

    Listlessness and depression are not part of ME/CFS. Post-Exertional Malaise is the central symptom, and OrthostaticIintolerance is another very common symptom of ME/CFS – either can force us to slow down and lay down a lot, but it’s for completely physical reasons. Otherwise a pretty good article, thanks 🙂

  • Trisha

    I really believe I have this disorder I suffer from extreme fatigue and never knew why and I have been searching for explanations. How would I find out if I have this please help

    • Shirley

      Chronic Fatigue Syndrome (CFS) occurs usually after trauma/surgery, or a really debilitating virus, such as mono. Stress plays a huge role in how bad your reaction is & how long the CFS lasts. If your immune sytem is weak and you have huge life stressors, your body will shut down. What is happening is that the brain will not produce your usual hormones and cortisol in large doses are released into your system (via hypothalmus pituitary axis/adrenal glands)Your immune system shuts down & you are not getting thyroid hormones therefor decreasing your energy, your body temperature is usually warm, sweating & then cold. These hormones also control your sleep paterns. You end up with sleeping lightly through the night & wake up exhausted & are exhausted throughout the day. If you are a woman, I would get your estrogen & progesterone blood levels checked because they are affected also. HRT meds can help with some of the symptoms.

  • Validator

    The author of the XMRV study you’re probably referring to, Dr Ian Lipkin, is currently involved in ongoing studies looking at other viruses in ME. ME has always been associated with viral infections and shadowed polio, even conferring immunity to poiovirus before it was eliminated in the West. Cocksackie, Echo, parvovirus, HHV6 are commonly found in ME patients and around 80% or more have acute onset with a viral infection. Foreign, pathogenic proteins have been found in spinal fluid and mutated viral particles in the gut. It is wrong to dismiss viruses as a whole as this article does.

    @Trisha, google “international consensus criteria”, “ME definition”, “Byron Hyde”, “canadian criteria” for criteria and go ask your doctor if he thinks you could have ME or CFS, if you disagree with him, see another doctor, good luck and don’t stop searching for answers.

    @Tiffani, you were possibly misdiagnosed, a case of ME is with you for life, you cannot “overcome” it, it is not psychosomatic but a complex multisystem neuro-immune disease – the emphasis being on disease; you cannot “think” or “behave” immune complexes and autoantibodies into existance. A subtype can have long lasting remissions which you’ve probably not been told about.

    Unfortunately CFS is or has become a garbage can for all unexplained fatigue with psychiatry and the rehabilitation squad at the forefront of maintaining conflation with differentially classified illnesses. This has been a disaster for patients, allowing dangerous, opportunistic quackery like “the lightning process” to abuses sufferers and further confuses and damage credibility. FOr anyone who is misdiagnosed, insist on more tests and be glad you don’t have ME but also consider a remission is not the same as a cure and recovery is a meaningless, much abused term for a chronic disease.

  • Pingback: PLEASE HELP! Respite Care for our Autistic Children because of Chronic Depression? « zpsychguide1333h()

  • Anonymous

    Thanks for the information.Really a great and useful piece of info.I am satisfied that you shared this useful info with us.

  • Alistair Taylor

    Thanks for the above information.I am satisfied that you shared this useful info with us.

  • Anonymous

    i think HIV AIDS Is deseasej

  • Sara Nakhai

    thanks for the article, Shafali!
    I would also like to add that according to some articles childhood abuse/maltreatment and chronic stress may also play a role in CFS.

    • Dr. Shefali Sabharanjak

      Hi Sara,
      Thanks for the tip. I’ll look into it. 🙂

  • Anonymous

    I like your site very much. You are a good blogger.

    • Dr. Shefali Sabharanjak

      Hi Anon,
      Thanks for your encouragement! 🙂

  • Anonymous

    hi. thanks for sharing this useful information, i really need this.

  • Thanks for a great blog. Really informative.

  • Lauren Michele


    I wanted to recommend a very resourceful doctor who specializes in fibromyalgia and CFS–Jacob Teitelbaum, MD–and he knows these conditions as an insider. He contracted CFS while attending medical school and had to drop out for a year to recover. In the ensuing 30 years, he’s dedicated his career to finding effective treatment. He’s written several books on the topic, including his latest, “The Fatigue and Fibromyalgia Solution” (Avery Penguin, August 6). For more info, check out his website, http://www.vitality101.com and to preorder, http://www.vitality101.com/the-fibromyalgia-and-fatigue-solution.



    • Anonymous

      I have read one of the Doc’s books. Some helpful info. But people write books to also make money. I would suggest if a person has chronic fatigue/fibromyalgia that they go to a Neurologist & have blood work done to rule out different diseases/immune difficiencies. You could be low on vitamin B /iron or have an auto-immune disease. All of which can make you very tired. They can also test for peripheral neuropathy, fibromyalgia, etc. And a sleep study is crucial to see if one is experiencing deep sleep and REM sleep or that they may have sleep apnea. The key is to find out why you are not getting restorative
      sleep, which can cause severe exhaustion. And add a stressful job/life, not eating well, etc. can all add to exhaustion. Pain from Fibromyalgia can be relieved with pain meds.but a tolerance builds up & you need more & more to relieve pain.Check out Neurontin/ Nortriptyline as alternatives for pain. Hope this info helps. RN

  • B

    Thanks for sharing the info.
    I have had CFS for 5 years now. I’m about 50 years old.

    I believe it happens in the lower brain (maybe basal)
    Is anyone else effected by temperature, if it gets hot, over 75 F it really bothers me. Cold too but I can keep warm and I’m OK.

    Also for me it feels like, if a normal person uses 1000 calories in a day, then I only have 600. Eating food makes no difference. If I use more then my 600 I get really sick. If I only use 600 every day I can be quite normal.

  • Pingback: ADHD Insights: Adrenal Compromise And Copper | CorePsych()

Shefali Sabharanjak, PhD

Shefali Sabharanjak, PhD, is a professional science and medical writer. She holds a doctorate in Cell Biology from the National Center for Biological Sciences. Clear and precise communication is her forte.

See All Posts By The Author

Do not miss out ever again. Subscribe to get our newsletter delivered to your inbox a few times a month.