CFS: Viral vs somatization

On 10/08/09, the NIH and Science through press releases announced the following remarkable information:  Consortium of Researchers Discover Retroviral Link to Chronic Fatigue Syndrome (CFS.) From Science on line:

Scientists have discovered a potential retroviral link to chronic fatigue syndrome, known as CFS, a debilitating disease that affects millions of people in the United States. Researchers from the Whittemore Peterson Institute (WPI), located at the University of Nevada, Reno, the National Cancer Institute (NCI), part of the National Institutes of Health, and the Cleveland Clinic, report this finding online Oct. 8, 2009, issue of Science.

“We now have evidence that a retrovirus named XMRV is frequently present in the blood of patients with CFS. This discovery could be a major step in the discovery of vital treatment options for millions of patients,” said Judy Mikovits, Ph.D., director of research for WPI and leader of the team that discovered this association. Researchers cautioned however, that this finding shows there is an association between XMRV and CFS but does not prove that XMRV causes CFS.

I was as surprised as others on reading this release. A disorder followed for over a century, commonly believed to be an emotionally-based, mood disorder (somatization) is found to have a viral “association”? Although the release states “association,” many readers are likely to read “cause.”  The vigor of the news releases and the enthusiasm of investigator comments sure lead one in that direction.

Surprised? Rather, shocked – reading simultaneous news releases from the journal Science (on-line version) and the NIH plus about association with the Cleveland Clinic. These are big time sponsors and investigators. The announcements are intended to be taken seriously. Yet I have doubts.   

The announcements and releases are a bit trumpety. But aren’t most such releases the same?  Yes, but then why the doubts here, which led to a skeptical blog like this.  Well, I saw a few problem clues – I thought I’d “share.”

But first, here are the present principles we use in thinking about CFS.  These principles compose a paradigm of the nature of CFS for which the new findings, if proved causal, would require a thorough re-structuring.

CFS has been recognized and described for over a century. It is commonly known by an array of different names, applied to the phenomenon’s syndromes, most of which have shared characteristics: chronic fatigue, fibromyalgia, da Costa syndrome/effort syndrome, neurasthenia (and even “pseudo-neurasthenia,”) myalgic encephalitis (M.E. – UK) chronic Lyme disease, multiple chemical sensitivities, Icelandic (Akureyrie) disease, subclinical hypothyroidism,  hypometabolism, hypoglycemia, candidiasis,  chronic mononucleosis/ Epstein-Barr disease.  Sharing symptoms and presumed differing only in prior associations have been shell-shock (WWI,) battle fatigue (WW II),) post-traumatic stress disorder (Viet Nam and subsequently,) and Gulf War Syndrome. The current paradigm includes all these as variants of somatization, somatiform illness, somatic conversion – all expressions of the same problem through a similar mechanism.

Each of those syndromes differs from others in the focus or dominance of the major symptom and the perceived cause. According to medical historians, these functional disorders were described as early as the mid-19th century (Charcot), and defined or elaborated and popularized by Freud in the early 20th as hysterical (blindness, paralysis, etc.) illness or conversion hysteria.   

Later 20th century manifestations were mostly vague physical symptoms, still expressive of somatization – a transfer of focus from emotional source to bodily functions and discomfort. The originating problem is thought to be too threatening to the person’s self image or identity to deal with consciously. Most physician observers detect signs of secondary gain in most patients.  

A signal finding of CFS people is a solidified lack of insight, and resistance to introspection and to pursuing psychotherapy or psychological investigation. Psychotropic drugs are generally unable to produce relief or a sense of help. This characteristic has made a diagnosis of underlying depression uncertain, and psychological approaches unsuccessful. But the lack of insight and the surface hostility to medical approaches cause a standoff between the affected and the medical system. Affected people drift easily into aberrant sectarian systems and methods, often claiming dramatic, though temporary results from them. Although most psychological approaches meet with resistance, some success is reported with cognitive behavioral therapy, perceived as non-threatening.

CFS uniformly spontaneously resolves over time. According to CDC, almost all cases are resolved by three years, although there are many of longer record.  If anyone has ever died with CFS, I’ve not heard of it. Nor have there been complications or sequelae. Coming close was a young man whose self-recorded history is on Phoenix Rising, one of the CFS web pages I came across. His is a lengthy story – not a typical CFS case – remarkable in its severity, duration, and  disability and even to cachexia.   

The major and signal symptoms have varied over the decades (centuries?) to conform to changes in medical heuristics and scientific explanations. Patient perceptions seem to accommodate to physician perceptions of what might be acceptable as physical illness. Despite this variation, in the early to mid 1980s, the Centers for Disease Control (CDC) synthesized a collection of major and minor criteria for following a population of CFSers for epidemiologic study. At the time, some experts estimated the affected US population at some 2 million.

The Incline Village epidemic

The current CFS wave started in about 1985 with a small population of patients in a small medical practice of two physicians in Incline Village Nevada, a resort collection of homes and condos on Lake Tahoe. The two physicians claimed that the symptoms of fatigue and poor mental functioning had affected the town in unusual numbers. They suspected the condition acted like a viral disease traveling through their community. Thus began a search for a viral etiology – Epstein-Barr, followed by HHV-6, then  mycoplasma, and other organisms. The affair led eventually to a national search and a sudden appearance of other clusters as well as widespread isolated cases.

Among multiple news stories in print and television, was a Newsweek cover story, identifying the phenomenon as an epidemic of mysterious origin, and ignoring the century-long identified history of mood disorder.

Another vogue concept in the mid-1990s was some ill defined adreno-pituitary-hypothalamic axis “imbalance” as seen by yet another array of mild abnormalities on various measurements including stress testing, hormonal assays, and blood pressure measurements, especially to tilt-table positioning.  These have led to other theories of vascular and pressure instability or electrolyte imbalance. Some of these studies bore the name of the future Director of the National Center for Complementary and Alternative Medicine, Steven E. Straus.

The problem has been that no laboratory or physical test abnormality had been found consistently in different groups or by different investigators.  There are over 4 600 references in Medline, and Google Scholar records over 400,000 references.  One would think there would be little left to discover. And, there is already a credible explanation for most cases of CFS – somatiform illness.

When the CDC completed its initial investigation, it found no evidence of a viral etiology, or even of an identifiable physical disease. To many of us, the sudden epidemic-like spread acted as much like a mass psychogenic illness as it did an infectious disease. At least two self-help, patient-organized CFS societies formed for patient education and advocacy, lobbying the CDC for research, and Congress for funds.   

CFS, lacking consistent definable characteristics, was somewhat arbitrarily defined by epidemiologists at the CDC in order to select a study population. Simply put, the symptoms are common to almost everyone at some time or other – fatigue, myalgia, specific tender “trigger points,” sleep disturbance, sore throat, mental fog, and inability to concentrate, all lasting a minimum of six months. The physical findings are also minimal – limited to perhaps a mild fever and/or mildly enlarged lymph nodes without pathology, tender muscle areas, but no specific objective finding, no radiographic finding, and no consistent blood or other lab test abnormality. 

The virus found by the current investigators was described as a xenotropic murine leukemia related retrovirus – like RNA virus previously found in men with aggressive prostate cancer. I know nothing about this virus or why they suspected it or how they happened upon it.  The article’s full text was still unavailable at the time of this writing. If I had read it, I still might need a virologist to interpret the lab methods and findings.

The report’s abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines following exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.

Note the description of a debilitating disease of unknown etiology… with no mention of current theory –  none of the reports so far has mentioned the current opinion on the nature of CFS and its other forms – somatization. All news reports contain only comments on theories of infection and the mysteries of CFS. Nevertheless, the researchers found the virus in blood and immune cells of 67 percent of CFS people as compared with 3.7 percent in normal people. That is impressive.  Determining what the XMRV is doing there is guesswork at this point.

Then two names on the news releases and the report caught my eye. The major research organization publicizing the discovery was the Whittemore-Peterson Institute for Molecular Biology. Reno is not far from Incline Village and the name D. Peterson – that turned out to be Daniel Peterson, the second physician in the original Incline report, along with Paul Cheney.  Over twenty years of searching for a cause of a phenomenon (an infectious epidemic) determined not to have occurred – and the search continues?  I could not help but take notice. And who is Whittemore?  He is a real estate developer in Reno who supplied the first $1.4 million for the new research institute to be at the University of Nevada Reno’s medical school, to be devoted to investigating neuro-humoral systems.  I suspected some family connection to CFS so looked through the releases and found a note that his daughter, 26, is…a sufferer from CFS.  None of this detracts directly from the weight of the experimental findings, but it’s just unsettling.

I do not know what will result from this work. Certainly, the work of 13 authors from four different research institutes must mean something. They could not all be deceived?  Eight authors from four countries were deceived in the original Benveniste homeopathy report. Then, tens to hundreds of investigators at NIH may have drunk of the NCCAM Kool-Aid by this time, believing at some point that there might be something worthwhile in CAM methods.  Funny things happen. I’m betting that either the work will not be replicated, or that some other innocent explanation such as an artifact of lab technique accounting for viral presence will be found. I estimate the odds at 80:20 (4 to 1.)

If the association is confirmed, the finding will have near-revolutionary implications for our understanding disease – particularly infectious disease.  If there is a confirmed model for such a vague set of symptoms signifying some occult infection limited to immune cells, which produces no repeatable cellular or antibody abnormality, no susceptibility to other infections (such as with HIV) and in which the sites of infection (immune cells) bear no relation to the sites of symptoms and produce no physical abnormality, I haven’t known of it.  Interesting times.

Posted in: History, Medical Academia, Neuroscience/Mental Health, Science and Medicine

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38 thoughts on “CFS: Viral vs somatization

  1. Mark Crislip says:

    I have always thought one part of my job is to find a pattern in the noise. It is all ID docs have: take extensive histories to try and discover what the patient has.

    I see my share of CFS patients, and they all have large psycological overlays. But.

    There has always been the subset who were high functioning, had an acute febrile illness, and never recovered. They give a different pattern than the borderlines or the somatiform illness..

    It has always sounded like an acute infection to me and I tell these patients it sure sounds like you had an infection, and I bet that something is continuing. And I have no therapy. I use a rock in a lake metaphor. The infection in the rock, the ripples are their illness, and I tell them it will fade with time. My bet is that in some subset of patients CFS have an infection yet to be discovered (my perpetual bias).

    The problem with many of these studies is that the final common pathway of many processes is CFS, so these patients are mixed in with the somatisizers and the depressed and the crazy.

    This fits with what retroviruses do, and I have been waiting for some clever virologist to find a new organism. As to new organisms, I have to learn one or two a month to keep up in the field. So a new retrovirus? Sure. I have yet to read the actual article, just my local papers description, and the interwebs. What I read seems cool.

    I bet 4:1 it will be reproduced. I bet it will be the answer for the subset that CFS patients with an acute onset.

    Dr. Sampson: 100 bucks to the James Randi Education Foundation by the loser that by 2015 it’s found to be cause of more than 20% of the CFS patients.

  2. JayHawkDoc says:

    What a terribly fascinating development. Great commentary. I, like Dr. Crislip, don’t necessarily agree with all your conclusions, but an excellent article nonetheless.

  3. jmm says:

    First, somatization hardly seems to me to be a scientifically useful paradigm, since it largely consists of “we can’t think of anything else”. What exactly is somatization supposed to mean, and how does such a label help either further research or treatment?

    Second, links between cfs and depression have by now been thoroughly debunked. Rates of depression in cfs patients are consistent with those seen in other serious, life-changing illnesses (eg MS, cancer), so cause and effect relationship seems obvious enough.

    Third, whole-genome expression profiling did show distinctive differential patterns in cfs patients: just because no single marker exists, abnormalities abound.

    As for resistance to psychological approaches, resistance is perfectly natural when it is patently obvious to the patient, if not to a doctor one has just met, that until recently one was a perfectly sane and balanced human being, and this psychological state has not suddenly changed just because of failure to recover from an infection, so why would one possibly expect psychological intervention to help? Cognitive behavioral therapy, on the other hand, is invaluable for developing coping strategies, which ultimately assist recovery by modifying lifestyle so as to avoid making the illness worse.

    Also check out the strength of the association with joint hypermobility and low blood pressure. The effect size is enormous. In comparison, this recent study is only the second largest correlative factor found. Do you have a theory linking somatization to that strong correlation?

    I do agree substantially with Mark Crislip: a failure of the convalescence process is not a bad model of the disease.

    Full disclosure re the passion of my ranting here: I have myself recovered from cfs over the course of 10 years. I have never suffered from depression or any other mental disorder. I guess I would be one of Mark Crislip’s outliers. There are more of us than you think: after learning that no effective medical treatment was available, I did the rational thing and stopped going to the doctor. Those seen most often are not necessarily representative.

  4. Deetee says:

    Great overview.
    Like Mark, I suspect that this virus may be a factor in a small subset of patients who get the CFS label.
    Might antiretroviral drugs have a future role?

  5. wertys says:

    Like the other commenters so far, I would also bet that some type of unknown infection could account for a proportion of CFS, just like the subgroup of that other poorly defined entity, Fibromyalgia Syndrome who do not seem to have any particular psychopathology and who respond almost instantly to gabapentin or pregabalin and immediately resume their premorbid activities.

    As one who has read Ioannidis et al I am appropriately skeptical of the leap from correlation to causation, and they would still have to fully characterize the virus and fulfil Koch’s Postulates, but at least it seems like a promising and potentially plausible finding.

  6. Wallace: You had me at hello. And lost me when you started claiming that there is no such thing as PTSD, but that these people happen to be somaticizers who happen to have combat in their past history.

    I dare you to develop the case that there is no such thing as PTSD.

    The symptom pattern does NOT fit these other “disorders.” Symptom patterns DO fit recognizable patterns: a combat vet who was a medic may suffer intrusive thoughts, disturbing dreams, etc., related to those a PHYSICIAN might have: blood-andguts, failing to save a life and feelign guilty and responsible; at the same time, a vet from the SAME conflict who had a DIFFERNT role will have DIFFERENT symptoms: if he jumped out of choppers, he will have intrusive thoughts, disturbing dreams, of FALLING. Not blood-and-guts and failing to save a life and begin guilty for failing to save a life. Fo rsomeone from the Korean war, COLD weather, but not fog, can trigger a spacey, dissociative state; for someone from the Vietnam war, a foggy morning, but NOT cold, can trigger a spacey, dissociative state.

    This does NOT fit the “medically unexplained symptom” (“MUS”) pattern.

    The MUS crowd does NOT booby-trap their home.

    The POWER of these problems leads many to drug use, and to suicide. That characteristic does NOT fit fibromyalgia, MCS, Environmental Illness, chronic Overachiever Fatigue Syndrome (I just mande that one up), etc.

    The WIVES of these combat vets KNOW that the husbands are not seeking secondary gain, and KNOW that the husbands do not learn these behaviors from others. In contrast, the wives are surprised and relieved to learn that there are others who do the SAME things.

    Husbands notice a certain pattern in intimacy relationships when they are married to woman who has been raped in their adulthood. There is a somewhat DIFFERENT pattern for the wives who were sexually molested by a family member in childhood.

    These women, and their husbands, discover these patterns. They are similar, but distinct.

    This is just the tip of the iceberg regarding the validity of PTSD, and the distinciton between PTSD and “MUS” conditions.

    I understand what you are talking about. I have received counseling referrals from docs who know they are dealing with MUS. For a fair portion of cases, things have been managed to the degree that the symptom complaints decreased, and the person began to move on twith their life. I have worked with vets trying to get a disability check — one guy explained how much he hated [derogatory term for Asians], just like some other Vietnam era vets — in a later meeting, I learned that he NEVER served overseas in Asia!!! He was just looking for the disability hook-up – I know. I understand. I have read Ioannidis. And Kock. And Bradford Hill. And Descartes. And Hume. And a lot more on science and causality. I have a lot of clinical experience with patients reporting MUS, or with the various diagnoses in their charts. I understand your point.


    Despite fakers, there is actually a clinical syndrome called PTSD.

    So please enlighten us and let us know how we all have it wrong about PTSD.

    God help you, and your patients, if you are in a position to “help” people with PTSD.

  7. daedalus2u says:

    I think the association with virus is likely to be real but non-causal. I don’t think the virus causes CFS, I think a persistent low NO state allows for virus to persist at higher levels in PBMCs. I think this is very similar to the increased levels of mycoplasmas also found in PBMCs of CFS patients. The clearance of intracellular debris (including mycoplasmas) is by autophagy, and this is triggered in PBMCs by increased ATP levels. The ATP level is controlled (in part) by the NO level (NO and ATP co-modulate sGC). Low NO levels will reduce clearance of intracellular infectious agents including mycoplasmas (and likely viruses too).

    In the brain during neuroinflammation, the low NO causes low ATP and reduces intracellular transport by ATP powered motors (i.e. transport down the axons). This shows up as reduced proton diffusion on MRI, as “white matter hyperintensities”. The cargo being moved up and down the axons entrains water and that shows up as anisotropic proton diffusion. White matter is mostly axons, so with less ATP, the movement is slowed so there is less apparent proton diffusion. This is non-linear and pretty complicated too. NO is the link between low O2 consumption, low blood flow, low ATP, neuroinflammation and white matter hyperintensities observed in essentially all neurodegenerative diseases (including neurosyphilis). I think this is the source of the “brain fog” that many experience following infections, ARDS, sepsis, major trauma, surgery and chemotherapy.

    The classic sign of CFS (exercise intolerance) is due (I think) to low systemic NO, which reduces mitochondria biogenesis so there are not enough mitochondria to support increased aerobic ATP production necessary to increase muscle metabolic activity above basal levels.

    If the virus is causal, then by looking at blood transfusion records it might be possible to find people who were transfused from someone with CFS. If the virus is causal, transfusion with infected blood should cause CFS. If virus can’t be isolated from individuals (who don’t have CFS) transfused with virus infected blood, then is more likely that people with CFS simply don’t clear the virus as people without CFS do (which is what I expect to see).

  8. MalcolmHooper says:

    The term CFS is not 100 years old it was introduced in 1988 against the wishes of the sick patients and some physicians who were treating people with ME, myalgic encephalomyelitis. Somatisation transfers the responsiblity for the disease to the patient and excludes him/her from any serious consideration of their illness. Somatisation has a long and much discredited history since it offered ‘explanations’ of illnesses like diabetes, Parkinson’s disease and multiple sclerosis before the physiological bases of these illnesses were identified. Somatisation is the last resort for those who will not think more deeply and collect data to help understand an illness. It gets difficult patients off the physicians list and reduces the need for any engagement with them.
    The term ME has been included in the WHO international classification of diseases, ICD-10, since 1969 under neurological illnesses chapter G 93.3. ME identifies muscle pain with inflammation of the brain and spinal cord and is a clear and meaningful clinical definition. The recent Canadian Consensus fills out this definition with an abundance of clinical signs to help any compassionate physician engage with this illness. Please reada and use it.
    Over 50 years of dedicated research by Dr John Richardson provides very strong evidence for an enteroviral related illness that is confirmed by the recent studies of Dr John Chia. There is compelling evidence that other rviruses may play a part partcularly those of the herpes family. Some 4000 papers addressing the biological basis of ME have provided definitive biological evidence for this complex chronic multi-system illness.
    Please read them and do not belittle sick patients by the use of terms like somatisation.

  9. jmm says:

    Here is the link to a study of the strongest correlation found for cfs It’s a small study, but that’s all you need when the effect size is that massive. The article includes a perfectly coherent etiology consistent with the data.

    Cfs is often triggered by serious infection, and as a result it has shown mild correlation with literally dozens of infectious agents. None is 100%, including the current striking results. The data is clear: there is no causal “cfs virus”. This is paradigm that has been thoroughly investigated, exhausted, and should be laid to rest.

  10. jmm says:

    Apologies if this is a double post, my last didn’t seem to show.

    Here is the link to a review of the strongest correlation to date with cfs, that with hypermobility and associated traits: It’s a small and simple study, but that’s all you need when the effect size is so large. It includes an entirely plausible etiology consistent with the data.

    In the face of this evidence, I find it irritating that far more resources continue to go into chasing viruses. Cfs is correlated with a history of serious infectious illness in general. It is therefore not surprising that it is frequently correlated with a great variety of specific viruses, and that some of these correlations will by chance be stronger than others. There is no causal “cfs virus”, this paradigm is dead and should be replaced by more productive ones.

  11. I agree with MedsVsTherapy. As a researcher in psychiatry who has worked on the topic I object to the concept that PTSD being a factitious. PTSD is a debilitating disorder with symptoms that distinguish it from conditions such as CFS. Patients with PTSD have experienced a traumatic event, such as combat, crime, accident or natural disaster, which leads to sensitization of the memory of the trauma. Though they share some symptoms with CFS, such as fatigue and anhedonia, unlike CFS, patients with PTSD have flashbacks and nightmares of the traumatic event, as well as avoidance of stimuli related to the trauma, hyper-vigilance, irritability and an exaggerated startle and fear response.

    I do suggest you look at the diagnostic criteria for PTSD before making any assumptions about it’s similarity or dissimilarity to CFS or any other condition.

  12. Rob Tarzwell says:

    I worked in a clinic and continue to collaborate with a psychiatrist who has been diagnosing and treating somatization using ISTDP (Intenstive Short-Term Dynamic Psychotherapy) for approximately 20 years.

    He has a growing database of about 500 cases of various forms of Somatoform Disorders successfully treated, with video-tapes of therapy sessions and pre-therapy and post-therapy questionnaires: Brief Symptom Inventory and Inventory of Interpersonal Problems. The sample includes a large subset of individuals with CFS.

    While we would never say that all cases of CFS are the result of emotional dysregulation, many are, and they can be successfully treated with brief dynamic therapies, not merely given new coping strategies, the current CBT approach. (Note, I think having good coping strategies is a good thing, but when a direct cure is possible, I think that’s even a better thing.)

    We created a pilot project at the QEII Health Sciences Centre’s Emergency Department in Halifax, Nova Scotia to provide a rapid access service to assess and offer brief therapy for somatization. The first patients’ data have been analyzed, and a paper was just accepted by the Canadian Journal of Emergency Medicine. It’s unfortunately not yet on PubMed, but a few papers produced by the centre can be accessed via PubMed:

    I. Short-term psychodynamic psychotherapy for somatic disorders. Systematic review and meta-analysis of clinical trials.

    II. Direct diagnosis and management of emotional factors in chronic headache patients.

    III. Chest pain–consider panic disorder.

    So, in our view, somatization is a very real phenomenon, can be directly diagnosed by psychodiagnostic interview, and in many cases can be cured or greatly relieved by psychodynamic psychotherapy. This includes CFS.

  13. Dr Benway says:

    I’ve had seen several patients struggle with what appear to be bodily hallucinations. Their head doesn’t feel right. Their stomach doesn’t feel right. They need to vomit to get something out that doesn’t feel right inside. As the psychotic episode fades, the unpleasant physical feelings seem to fade as well.

    I’ve also seen a few patients with epilepsy or hypothalamic tumors who have auras involving nausea.

    So the body affects the mind which affects the body.

    It’s true that “somatoform” is a diagnosis of exclusion. It’s not a satisfying diagnosis because it doesn’t explain what’s causing the discomfort. But the good news is it’s not cancer.

    I find it unfortunate that people feel insulted by a diagnosis that suggests the brain might be doing something weird to cause the symptom. To me it’s all the same, suffering. There’s no moral stigma.

  14. trrll says:

    “Somatization” is a name, not an explanation. That doesn’t mean that it is wrong; after all, like “psychogenic,” it is just another way of saying “a poorly-understood cause involving the physiology of the central nervous system.”

    Nevertheless, I’ve long suspected that a number of poorly-defined illnesses will turn out to be retroviral. After all, if people with HIV didn’t die of unusual infections, the virus would almost certainly never have been identified. And HIV infection can persist as a chronic infection for many years without the emergence of AIDS, while apes with HIV typically never develop any clear signs of illness at all. It seems unlikely that all chronic retroviral infections must be either ultimately lethal or completely harmless, suggesting that there is probably a whole family of retroviral infectious diseases for which the symptoms fall somewhere in the middle ground. Will this turn out to be the first such low-grade chronic retroviral illness to be identified? The news reports I’ve seen have been fairly conservative in reporting the finding as an association rather than a cause.

  15. jmm says:

    I agree that there should be no moral stigma associated with suffering whose origin is psychological. I just don’t think that this is the case with the typical cfs patient, and that this diagnosis is therefore unhelpful either for research or treatment. Please point to the data if you think it exists.

    How can one possibly distinguish between a physiological disease of yet-unknown cause and a somatiform disorder? If someone could answer this question in a sensible way, I’d be willing to take somatiform disorder more seriously as a diagnosis.

    This post bordered on the absurd in hinting in the direction that a patient’s resistance to psychiatric treatment should be interpreted as evidence that they are insane…

  16. pmoran says:

    jmm: “How can one possibly distinguish between a physiological disease of yet-unknown cause and a somatiform disorder? If someone could answer this question in a sensible way, I’d be willing to take somatiform disorder more seriously as a diagnosis.”

    In my patient population, patients liable to be labelled with CFS or fibromyalgia or MCS usually had multiple OTHER episodes of exhaustive negative investigations for symptoms involving differing bodily systems — sometimes to an extreme degree.

    There was also often an extreme disparity between the stated disability, and obvious, ongoing, blooming health. You don’t ever want to get a condition that makes you feel like you have terminal cancer or advanced pulmonary TB , but which leaves you bouncy, ruddy of complexion and gaining weight, because doctors may well be fooled. We can’t help it — we are so accustomed to the more usual illness accompaniments. .

    Also, medicine is above all a practical discipline. A diagnosis of somatiform disorder has certain prognostic and therapeutic implications. The patient may at least be helped to cope while the body and mind becomes less sensitive in so many ways with age and as stressors come and go.

    How does it help to attribute an illness to an unknown, undiagnosable, potentially untreatable disease state? The doctor should be keeping part of his mind open, anyway, and be preapred ot investigate further with little prompting.

    This is one of the reasons why MCS is one of the most ill-conceived pseudo-diagnoses. It has no useful therapeutic implications and can condemn the sufferer to escalating disability and social isolation.

  17. Rob Tarzwell says:

    I strongly disagree that Somatoform Disorders are diagnoses of exclusion. They can be directly diagnosed through emotion-focused interviewing, through paying attention to readily observable and repeatable signals manifest in the patient’s bodily reaction to internal emotional stimuli.

    In my experience, patients are often not resistant to exploring emotional factors in their symptomatic presentations. Those who are resistant have often had extremely negative physician encounters where they have been essentially blamed for their problems. Once they realize that an empathic and properly trained assessor has no stake in forcing a diagnosis, they’re often quite relieved to finally have sensitive attention paid to their emotional lives.

    I’ve never once told patients they are somatizers. Through an exploratory process, we both come to discover whether they are or aren’t in a specific, reliable, repeatable manner.

    Here’s a link to a 2005 paper in the Journal of Family Practice on direct diagnosis of somatization through emotion-focused interviewing.

  18. lab001 says:

    Your article must be some kind of joke, surely? You have not read the paper. You have not read the paper? You write a lengthy piece rubbishing a paper published in “Science” and you haven’t read it? And the name of this website is….?
    And you make some inference with regard to the fact that the study wouldn’t have taken place without financial assistance from the mother of a woman who has been ill for many years. Are you suggesting this woman would be glad to have fake results of some kind in order to “help” her daughter? Are you somehow inferring that Judy Mikovits – 20 years’ experience of HIV – and Robert Silverman – even longer experience in cancer research – have somehow manufactured data and fooled that slipshod, second-rate journal “Science”?
    There are many factual inaccuracies contained in your ramblings but it is clear to anyone with a modicum of objectivity that you are not the type to accept that you might just be incorrect on certain multiple points. You lost me at the point you revealed you hadn’t read the paper.
    It’s a cosmic joke isn’t it? These poor patients – the ones with a well-defined chronic disease and not the depressives given a “CFS” tag by lazy or incompetent physicians – sit in a consulting room with people brimming with the type of attitiude you display. Which one is deluded?
    I suggest you rename your site “ArchaicBeliefsSpoutedWithoutReadingNewEvidenceBasedMedicine”.

  19. brightleaf says:

    Rob Tarzwell essentially hits the nail on the head regarding resistance to emotional factors often being as a result of the patient feeling blamed for their condition. This is extremely unfortunate, because time has to be taken to put the patient at ease in this regard. Some of them have had very condescending and negative interactions with the medical profession and expect my interactions with them to go poorly.

    However, I am disappointed by what appears to be the overuse of somatization by physicians who are not qualified to diagnose it. This is a weighty diagnosis which should only be given if any other conditions which could cause a patient’s symptoms have been ruled out, because if given incorrectly, it can hamper investigations and doctor patient interactions.

    Additionally, a physician should not start, a priori, with a bias about the psychology of a patient because they carry a diagnosis of CFS. I have found that a number of patients have been misdiagnosed because they have not had a full work-up. This may include a neurological exam, blood pressure monitoring sitting and standing (orthostatic intolerance and blood pressure dysregulation can produce the nausea, fatigue and “brain fog” some patients complain about), questioning the patient about their sleep (some of them have sleeping disorders), etc. As a diagnosis of exclusion, often not enough exclusion is being done, and I feel this is because CFS itself carries a stigma which portions of the profession won’t admit to. I won’t even entertain CFS as a true diagnosis on the basis of a blood panel as the sole method of exclusion, but incredibly this is actually being done.

    Care must also be taken to separate out the emotional reactivity associated with the losses that accompany CFS and negative experiences as a patient from somatization. I have to say that somatization is not a diagnosis I give lightly or often, and again can only express a disappointment for how often it seems to be used as a heuristic device rather than as a true explanation.

    As for the research, if it is consistently replicated in the patient population then somatization will cease to be a useful construct in affected individuals and will necessarily be abandoned as the rigors of science requires. I do feel that perhaps some individuals will have trouble revising their view of the condition if this is the case, and some of the criticism of this research appears to be a form of resistance in itself. This is preliminary stuff, we don’t know yet, let’s see how it pans out instead of defending our pet theories and let science take care of what is objectively the case.

  20. daedalus2u says:

    That article on joint hypermobility is quite interesting. It turns out that NO generated by deformation of tissue is the major control mechanism for determining the stiffness of that tissue. That is the control paradigm for bone, for blood vessels, for ligaments. When the basal NO level is low, it takes greater deformation to produce the same NO signal to trigger increasing the stiffness of the tissue. The “setpoint” for tissue stiffness is lowered by a reduced basal NO level. This is why low NO causes osteoporosis (bones need to deform more to achieve the same NO level) and lax joints (the ligaments have to deform more to achieve the same NO level).

    Thus joint laxity due to low basal NO is consistent with the low NO causing insufficient mitochondrial biogenesis and leading to exercise intolerance.

  21. Recovering Cam User says:

    As both a longtime CFS patient and an avid reader of this blog, I was very curious to see how the latest research would be addressed here. I am seriously disappointed by Dr. Sampson’s post, which betrays a broad ignorance of research done into CFS and reflects the cognitive biases of entrenched perspectives far more than the science-based perspective this blog is supposed to have.

    FWIW, it is the attitude expressed by doctors such as Sampson over the last 15 years which drove me deep into the arms of CAM in search of help with my own sudden-onset CFS.

    I will be watching closely to see if this research is replicated – if it is, and effective treatments for CFS are developed as a result, I suspect that the CAM world is going to lose a huge portion of their business as patients who have been left out in the cold by the medical establishment suddenly get the attention they have long needed.

  22. jmm says:

    pmoran, if you look at the link I posted before I hypermobility, you will see the physiological reason why cfs patients tend to be hyperenergetic always-on sort of people before they get sick. What you see afterwards may strike you as bouncy, but is sometimes a pale shadow of what the person used to be. In addition, a cfs patient will typically “rise to an occasion” including a visit to a doctor’s office, and pay later for the overstimulation that was induced. I do understand the natural bias of doctors here about “looking sick”, but it does serve cfs patients very badly.

    brightleaf, thank you for your thoughtful post. If all somatization diagnoses were in hands like yours, I would not object to them.

    lab001, thank you for telling it like it about the quality of the post. SBM should not host a post about cfs from someone unfamiliar with the state of scientific research about cfs.

  23. jmm says:

    Rob Tarzwell, I would be persuaded if and only if you have clinical trial data showing that dynamic psychotherapy is effective for patients meeting strict cfs diagnostic criteria.

    Cfs is a disease made worse by stress, especially emotional stress, so the protocol you cite would almost always classify it as somatiform. Made worse by emotional stress does not equate to be caused by emotional stress, however. This causal leap is entirely unfounded.

    There is a danger that psychotherapy is traumatic in itself and could make things worse by increasing levels of emotional stress. Throwing together patients for whom emotion makes things worse together with those for whom emotion makes things better as BOTH somatiform may not be wise when sending them both on to the same treatment options.

  24. Rob Tarzwell says:

    jmm, what gives you the idea that the psychodiagnostic interview “would almost always classify it [CFS] as somatiform (sic)”? What experience, knowledge and training have you had in the technique?

    One of our most important tasks at the Centre (Centre for Emotions and Health, was specifically to exclude somatization as a driver in CFS where we found no convincing clinical evidence supporting this.

    You’re right to wait for clinical trial data specifically diagnosing CFS by independent criteria. The Centre currently collaborates with a Physiatrist (Physical Medicine and Rehabilitation Specialist) who independently establishes the diagnosis using the most recent CDC criteria. You can contact the Centre director (Dr. Abbass) through the website if you’re genuinely curious about this. I believe there is an intention to publish specifically on CFS, though I’m not certain whether subjects are being enrolled at present (haven’t worked with the Centre since ’06).

    I agree there is a danger that psychotherapy can be traumatizing. Surgery can be pretty dangerous too. Those are not contraindications. The key to minimizing the risks, unsurprisingly, is to use skilled and competent therapists and to ensure that there is an indication for therapy.

    brightleaf is exactly the kind of MD we like to collaborate with in terms of establishing the diagnosis with precision and then tracking symptomatic shift with emotion-focused psychotherapy and validated scales. We haven’t got the budget for independent raters yet to administer those scales, which would be a great boost, but we do what we can. The brightleafs of the world are both tuned into the patient’s emotional welfare and commited to scientific precision in diagnosis.

  25. godf says:

    Science based medicine?

    Yet you seem uninterested in science which does not support your own prejudices (pardon me – would require a paradigm shift).

    You paragraph starting: “CFS has been recognized and described for over a century” seems to speak with a misplaced certainty about illnesses which are still poorly understood. Some people like to use the language of ‘science’ while maintaining the faith based certainties of a less evidence based belief system. I think this can serve to discredit science in the eyes of many, when it should serve only to discredit the writer.

    “A signal finding of CFS people is a solidified lack of insight, and resistance to introspection and to pursuing psychotherapy or psychological investigation. Psychotropic drugs are generally unable to produce relief or a sense of help.”

    I’ve been trying to source what would make you think ‘a signal finding of CFS people is a solidified lack of insight, and resistance to introspection’, and haven’t been able to find anything. Again, you make this statement very confidently – do you have any reason for doing so?

    Maybe they’re resistant to pursing a psychological response to their illness because so many doctors seem to view CFS as a psychological illness based upon only the flimsiest of evidence. Cancer patients are also highly resistant to receiving psychological intervention as their primary form of treatment.

    My girlfriend and I have suffered from CFS for over seven years, and been repeatedly psychologically examined, without any problem ever being identified. Throughout this period of being treated as if I was crazy, I have read about a lot of psychology. It has not helped me with my condition, but has helped me understand the way in which so many doctors respond to it.

    It must be a psychological strain having to treat patients with conditions we do not understand, and we all seem to have an inbuilt bias towards blaming those who suffer for their hardships. Especially now that we’ve gone through a period where it was seen as acceptable to treat those with CFS as if they were just being lazy and needed to push themselves to get better, many doctors will not want to move away from a primarily psychological model, as that would require them to come to term with the injustices they’ve imposed upon their patients, often through quite heated relationships.

    I certainly don’t think that we can say with any confidence that CFS is primarily caused by a virus, but to pretend we have any more compelling proof that CFS is primarily psychological is to seriously distort the current state of the evidence. When the available evidence is so uncertain, we should accept our ignorance, not give free reign to our prejudices.

    A lot of doctors seem to think that, unless there’s firm evidence an illness has a physical basis then it can be safely assumed to be primarily psychological. This is not a fair assumption to make; especially given the additional hardships which being classed as psychologically ill will create for patients. I was just reading a piece by an American doctor who was claiming that CFS patients ended up developing PTSD as a result of the way their doctors treat them. Certainly many doctors, and this blog post, seem to move far beyond the modesty required by science in the claims they make about CFS, apparently without any thought of the difficulties their assertions may cause others or the discredit they do to science.

  26. jmm says:

    Rob, I took it directly from the link you sent. Diagnosis made when emotions make symptoms worse. Or better. Any time emotions affect symptoms at all. That’s what the linked article said, I am going by that. I do hope that diagnosis is, in practice, more nuanced than that.

  27. Rob Tarzwell says:

    jmm, “That’s what the linked article said.” You’re pretty quick to grossly oversimplify and then dismiss the oversimplification.

    Yes, it’s quite a bit more nuanced than that, and if you read the article attentively, you’ll see that for yourself. I’m not interested in rebutting a straw man.

  28. Harriet Hall says:

    Green sickness that affected young virgins was considered a hysterical “nervous” disease and one doctor recommended that sufferers should “live with men and copulate. If they conceive, they will recover.” Turned out to be iron deficiency anemia, and pregnancy would have made it much worse! But it was easily shown that these patients were iron deficient and that iron was an effective treatment. Science worked.

    Ulcers were thought to be psychosomatic and caused by stress. Then Helicobacter was identified as a cause. It took only a few years from speculation to routine treatment. Science worked.

    If science can determine a physiologic cause for conditions like CFS, we will all be delighted. But we will have to see good evidence. Meanwhile, Morgellon’s sufferers show their doctors pieces of lint and think they are parasites, and somatization is a recognized psychiatric syndrome. Not everything people complain of is a diagnosible physical illness. It is tempting to jump on preliminary studies like this one and raise hopes prematurely. I will keep an open mind and watch future developments with great interest. Science works, and time will tell. Meanwhile, I think many of us will agree that these vague syndromes are being over-diagnosed, muddying the scientific waters so that it is difficult even to define what is being studied.

  29. geo says:

    Science worked, but as you pointed out, Doctors failed their patients. They decided that illnesses were psychosomatic based on little more than their own prejudices. My Grandfather suffered from stomach ulcers, and spent his life being told that this terrible pain was his own fault for getting too stressed and not relaxing enough (what a stressful thing to be told). He died before the truth was discovered.

    We do not know that CFS is a physical illness, but that does not allow us to assume it is a psychological one. We do not know enough to have developed a useful paradigm, never mind feel hesitant about changing it as new evidence comes to light.

  30. Robin says:

    I admit to thinking chronic fatigue is fake too, without really knowing that much about it. But, the explanation of somatization rings alarm bells.

    My mom was ill for decades to the point of disability. Dr. after Dr. told her it was stress or psychosomatic (none of them were Psychiatrists.) She fit the profile of a patient who’s physical complaints shifted from symptom to symptom, who described her problems emphatically, and for whom no physical basis could be found. In high school I spent a couple of years being angry with her about it and demanding she see a psychologist. She refused. Years later she was diagnosed with Sjogren’s syndrome. It wasn’t presenting abnormally and was attacking her organs.

    I suspect some people with chronic fatigue are malingering, but, probably many are just are misdiagnosed. Others may have that retrovirus. Ten minutes on pubmed shows that these people have a lot of hardcore labwork. Natural killer cell dysfunction? Abnormal SPECT scans? Are the patients faking those too?

    Some of your assertions are just wrong. Somatization does respond to anti-depressants according to literature and a Psychiatrist I spoke to about my Mom. And there was a girl that died of fatigue named Sophia Mirza (google is your friend!)

    I know firsthand the emotional damage that can be done by a somatization label on a truly sick patient. I suspect you would have been one of those physicians who summarily dismissed my mother. Keep an open mind.

  31. Prometheus says:

    The study (Lombardi et al 2009) was published as a ScienceExpress online article, which makes it difficult to access if you don’t have a personal subscription to Science (I do). Fortunately, it also means that the article didn’t include the methods or the results, which are published as a separate “supplemental” which is available to anyone (

    One thing that doesn’t show up in any part of this article is a comparison between the subjects with CFS and the “healthy control” group. Thus we are left wondering if the difference is due to the presence/absence of CFS or to some other difference between the groups (e.g. age, gender).

    Rather than try to predict what the future will hold, I’d like to see another group replicate these findings. As they stand right now, there are too many unanswered questions about their results.


  32. bonafide says:

    WPI posted the following on October 17 on their Facebook page.

    “XMRV is strongly linked to patients with ME/CFS. This initial finding was confirmed in three different laboratories, the National Cancer Institute, the Cleveland Clinic and the Whittemore Peterson Institute.”

    “Patient samples were donated from different locations around the US. This was not one cohort. All patients met the Fakuda and Canadian definitions for CFS and the study included age and sex matched controls with zip codes but Science did not feel that information was important to this publication. Not all patient samples that were positive had the biological markers of low NK cell function and RNase L defect.”

    “The importance of this finding is two fold. One that XMRV is an infectious retrovirus found in significant numbers in the blood of people who are ill with CFS and only in a very few without symptoms of ME/CFS. Number two is that it was found in 4% of healthy controls which means that 10 million Americans may be infected with this retrovirus.”

    “What you ultimately call this disease is not important. We must now try to understand how this virus is acquired and how that relates to disease and immune deficiencies. Human infectious retroviruses are not ubiquitous or benign. This virus should not be confused with benign endogenous retroviral particles that we all have in our genome. This is only the third human infectious retrovirus found to be replicating in the blood of humans to date, the other two are HIV and HTLV-1 & 2. It is a gamma retrovirus not a lenti retrovirus which means it is a simple vs. a complex retrovirus.”

  33. Wayne says:

    I just became familiar with this site a week ago or so, and thought it might be a useful place to peruse scientific medical information, especially as it relates to my decades-long struggle with ME/CFS. After seeing this “opinion piece” (totally unrelated to scientific-based medicine), I doubt I’ll be coming back here again.

    I can’t even believe this site (or any other site) would publish such a piece. It seems to epitomize an example of somebody writing about something they know almost nothing about. The author didn’t even read the Science article, knows nothing about the virus, and wouldn’t know how to interpret the findings???? And he obviously knows nothing about the physiology of ME/CFS even though hundreds, if not thousands of scientific articles have been written about it.

    To the editors of this website: Why in the world would you publish an article like this that is so filled with scientific inaccuracies? I find it puzzling, and quite frankly, pretty shocking. I can’t help but believe your reputation will be seriously tarnished by your decision to publish this.


  34. Mary says:

    In the main, “science-based medicine” as concerns chronic fatigue syndrome is an oxymoron. I presume when “science” sets out to study an illness, it looks at symptoms and tries to determine causes. It shouldn’t start out by branding patients malingerers or throw out words like somatization before doing even minimal research into causes.

    One of the most debilitating features of chronic fatigue syndrome – ask anyone claiming to suffer from it – is something unfortunately called post-exertional malaise. This term is unfortunate (like the name “chronic fatigue syndrome” itself) because it does not begin to describe the acute exhaustion which follows often rather minimal exertion, which takes days to recover from, but it’s the word “science” has given us.

    Okay. Well then, does “science” then study patients to see if there are objective findings for post-exertional malaise? No????? In fact, I believe the only significant research being done on POST-exertional malaise is being done at the Fatigue Lab at the University of the Pacific at Stockton, California. (see They are doing what should have been started over 20 years ago, performing exercise stress tests one day, and then following up with an exercise stress test the next day – POST-exertion.

    Their findings are extraordinary in that they are showing exactly what CFS patients have been complaining of for over 20 years – severe unprecedented debilitation the day AFTER exertion. . Many of the initial tests show abnormalities, but the most extreme findings occur in the after (or post) exertion tests.

    Why hasn’t “science-based medicine” looked into this before? Is it perhaps because it already made up its mind that the condition didn’t exist, so saw no reason to investigate? Like the author of this article. It’s inexcusable that it has taken a small poorly-funded lab to do this most basic research. Somatization indeed.

  35. MaxJerz says:

    I completely agree with Recovering Cam User. While I don’t have CFS, I do have another chronically misunderstood disease (Chronic Migraines). Like CFS, Migraine sufferers often bear the blame for their illness and often hear the word “somatization” thrown around. Like CFS, there is no “test” for Migraine.

    It’s exactly this sort of thinking that drives chronic illness patients away from the science-based medical system that fails them, into CAM which will at least attempt to treat them.

  36. pmoran says:

    “Their findings are extraordinary in that they are showing exactly what CFS patients have been complaining of for over 20 years – severe unprecedented debilitation the day AFTER exertion. . Many of the initial tests show abnormalities, but the most extreme findings occur in the after (or post) exertion tests.

    Why hasn’t “science-based medicine” looked into this before? Is it perhaps because it already made up its mind that the condition didn’t exist, so saw no reason to investigate?”

    PM It is not so clear-cut. This does not advance understanding of the condition. They are predictable subjective responses in anyone who has such expectations and, indeed, possibly to be expected in anyone who has had a period of minimal physical activivty for any reason.

    Why do you imply that there has been no investigation? What available test or investigation has NOT been performed on CFS sufferers? They are the most investigated group of patients on earth.

    The problem is that while many weak to moderate associations have been found in lengthy study, there is none that so far offers a satrifactory explanation for all cases, let alone led to a relaible cure.

    Nevertheless I think we all agree that the diagnosis of somatisation should not be made lightly.

  37. bonafide says:

    pm: “we all agree that the diagnosis of somatisation should not be made lightly.” Apparently not:

  38. ericaverr says:

    I have looked for the science in this article, but I can’t find it.

    1) “I’m betting that either the work will not be replicated, or that some other innocent explanation such as an artifact of lab technique accounting for viral presence will be found. I estimate the odds at 80:20 (4 to 1.)”

    The CFS study was itself a replication of the original cancer study done by Silverman at the Cleveland Institute. Silverman used a polymerase chain reaction (PCR) test to identify the retrovirus in prostate cancer patients with a specific genetic sequence. Since the Silverman study has been replicated, and because XMRV was not found to be an artifact of that test, there is no possibility that XMRV could be an artifact of the PCR test used in the CFS study.

    2) “I know nothing about this virus or why they suspected it or how they happened upon it.”

    The virus was discovered in a subset of cancer patients who showed an elevation of a specific low-molecular weight viral pathway known as the 3′-5′ Rnase L pathway. CFS patients also show an elevation in the Rnase L pathway. As this is a clinical finding which is not present in the general population, the connection was made.

    As for XMRV’s role in CFS, Dr. John Coffin (a highly respected retrovirus researcher at Tufts) has not been able to come up with a role other than causation. It’s fairly simple: XMRV, like the other two infectious human retroviruses, is not found in the general population. Therefore, it cannot be a consequence of the illness. (Opportunistic viruses must, by definition, be widespread.)

    3) “The problem has been that no laboratory or physical test abnormality had been found consistently in different groups or by different investigators”

    Staci Stevens has demonstrated exercise intolerance measuring oxygen consumption levels after a standard 2-day stress test in 100% of CFS patients. None of the controls shows the same pattern of decreased oxygen consumption.

    4) “If there is a confirmed model for such a vague set of symptoms signifying some occult infection limited to immune cells, which produces no repeatable cellular or antibody abnormality, no susceptibility to other infections (such as with HIV) and in which the sites of infection (immune cells) bear no relation to the sites of symptoms and produce no physical abnormality, I haven’t known of it. ”

    There is no confirmed model for the above, but that is only because you have presented us with a straw man. CFS patients have been shown to have increased susceptibility to other infections (herpes viruses, EBV, bacterial infections, etc.). Immune system abnormalities (low NKC function, shift from Th1 to Th2 immunity, elevation of Rnase L pathway, etc.) have been well documented. Physical abnormalities include fever, swollen glands, hair loss, pallor, flushing …all of which were part of the original case definition.

    Last of all, you have completely missed the true significance of the XMRV study, which is not that the intransigent sufferers of a “mood disturbance” are trying to redefine medicine. The implication of a study revealing a retrovirus in nearly 100% of people suffering from a chronic, debilitating illness (but not in the general population) is that because people such as yourself have defined CFS as a somatization disorder, we now have an untreatable, infectious, carcinogenic and potentially lethal retrovirus (Sophia Mirza died of CFS in 2006) contaminating our national blood supply.

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