A Test for Chronic Fatigue Syndrome
huffingtonpost.com
huffingtonpost.com
The committee argues that, "ME/CFS is a serious, chronic, complex, multisystem disease that frequently and dramatically limits the activities of affected patients. In its most severe form, this disease can consume the lives of those whom it afflicts. It is 'real.' It is not appropriate to dismiss these patients by saying, 'I am chronically fatigued, too'".
Theodore Ganiats, one of the committee members wrote, "The literature review found sufficient evidence that ME/CFS is a disease with a physiologic basis. It is not, as many clinicians believe, a psychological problem that should not be taken seriously" [2].
The committee proposed new diagnostic criteria and a new name "systemic exertion intolerance disease".
In my opinion, getting past the psychological and psychosomatic theories of CFS is a huge step towards meaningful research funding to address this disease. The IOM publication [1] and committee members efforts to disseminate the findings of this report [2,3] to the medical community is a big step forward.
[1] http://www.iom.edu/Reports/2015/ME-CFS.aspx [2] http://annals.org/article.aspx?articleid=2118972 [3] http://jama.jamanetwork.com/article.aspx?articleid=2118591
While I'm happy for people here who have resolved whatever underlying psychological and/or emotional issues that were causing them problematic fatigue, the experience of many CFS/ME patients suffering post-exertional malaise is generally much more specific in the type of fatigue suffered, and much broader in the range of symptoms experienced.
One example of cutting edge CFS/ME treatment research focuses on the use of rituximab, which has been pioneered by Norwegian oncologists who discovered its effectiveness accidentally, and are now pursuing a phase three trial after successful smaller trials. There are a variety of other approaches being explored too (e.g. Pridgen & anti-virals with anti-inflammatories, Montoya at Stanford, and so on).
The work on rituximab, and other research (e.g. this POTS research on autoimmunity: http://www.dysautonomiainternational.org/blog/wordpress/new-...) suggests autoimmunity, but much more research needs to be done.
A serious disease needs serious research, and serious research requires serious funding. Psycho-social theories do a disservice to those suffering from a very real, very debilitating illness, and the sooner these distractions can be dispensed with, the better.
Regarding the rituximab trial, it's primary end-point was actually negative. It will be interesting to see if the results are replicated.
Do you have a source for your comment about the end-point being negative? The last interview I read with the researchers suggested they were still getting results in 2/3rds of patients, they were optimising their dosing schedule, and were fairly upbeat about their prospects for their phase three trial. I'd be interested to read more discussion on their work though.
To dismiss any emotion-based causes/treatments as "woo" is to claim that there is no link between emotional activity and physiological functioning.
There's every bit of difference between saying to a CFS patient "it's all in your mind, go and get a haircut to make you feel better", and saying "your emotions - particularly your subconscious ones - play a huge role in your physiology, you can improve your health by improving your emotions using this technique for which there is a solid track record of success."
Psycho-social theories do a disservice to those suffering from a very real, very debilitating illness, and the sooner these distractions can be dispensed with, the better.
No, it's the refusal to consider such theories and include them in proper research that does the disservice to sufferers. For as long as this continues to be the case, a genuinely effective treatment for CFS will not be found.
I should emphasise: I don't argue for a psychology-only approach to treatment, far from it. My improvement is as much a result of physiological treatments as emotion-based ones. My argument is that both are important, and one without the other will not work.
But they have been considered. And studied. And found wanting. It is not, anecdotes notwithstanding, possible to "improve your health by improving your emotions using this technique for which there is a solid track record of success". There _isn't_ a "solid track record of success. That's the whole point. If there was, we wouldn't be having this conversation, because everyone with CFS would be cured several times over by now.
That's why there is a need for real (read: effective) treatment. If I, or any other of the many sufferers out there, could heal ourselves through some emotional technique then we would be _over the moon_. But we (and many others) have read the books; tried the techniques; and are right where we started: wanting real funding for real research for a real disease.
Physiological treatment will work alone, just like they have for stomach ulcers, and countless other illnesses that were previously attributed to vague, non-scientific explanations. We just need to do the research.
I think the problem with CBT for CFS is that it has an incorrect etiology, and more effective psychological treatments will likely become available.
From what I can see, CFS definitely can be cured by "some sort of emotional technique". It's just that a lot of CFS patients simply don't want to believe it, so they essentially end up doing the exact opposite of what is required to recover, resulting in further illness rather than recovery.
How much of this is due to your personal experience vs survey of the data? "Cure" is a very powerful word. There are several examples of CBT providing beneficial results, but nowhere near complete cures as far as I know. It's important to separate our personal experience from the data about a disease with possibly heterogeneous patient population.
For the record, I have no doubt psychological state has an effect on ME/CFS symptom severity.
Unfortunately there is no effective, evidence-based treatment that is based on a sound etiology of the illness. However if you understand the etiology you can certainly "hack" your brain to fully recover from CFS like myself and many other patients have done.
Sorry but this is dangerous and insulting to a lot of CFS patients. I wonder how far down you were as I've seen several examples of people driven to near suicide if they had the energy. These are people who are desperate beyond comprehension and will literally believe anything put in front of them.
You may have been able to hack yourself better but you are going down the route of victim blaming here suggesting "if only you believe it will work".
CFS seems to have a lucky group who recover and then become almost evangelical about their approach, thinking it will work for everyone. Often this treads dangerously close to pseudoscience and how they know more than doctors.
9 times out of 10 a book or audio course is not far behind.
If there is a subset of chronic fatigue patients that are helped by your method, great. But you don't seem to accept that some CFS/ME patients have tried and have not responded to those sorts of techniques. They did believe it. It didn't work. They need proper medical treatment, in the same way (say) MS patients do, not blame for "simply not wanting to believe it".
Please try and accept that there's more nuance to the situation, rather than painting everyone with the same brush.
Also, I'm not really sure if patients have "tried and not responded" to these techniques. (If you're talking about CBT, relaxation or positive thinking, that is not what I'm talking about). I think you're perhaps assuming that because CBT isn't very effective that no psychological treatment is effective. That's like saying that because one drug doesn't cure a disease then no drugs will work.
>A lot of CFS patients bring up the subject of stomach ulcers. It's almost as if they want to prove that psychosomatic illness doesn't exist.
And we're the ones with the negative attitude?
Anyway, I'm sorry you suffered from a psychosomatic illness.
I see that you've written a book (http://www.amazon.com/Mind-Body-Health-Stress-Tolerance-Jame...) and have articles covering your views on CFS & recovery here: http://www.mind-body-health.net/cfs.shtml. You say:
>However, recovery is possible in all cases, even for the most severely disabled patients, and in many cases this can be achieved by a relatively simple change in lifestyle
You appear to have reached that conclusion by extrapolating from positive, lifestyle magazine style reports of CFS recovery based on a range of dubious treatments (which you put down to the placebo effect) -- along with your own experience.
Can I suggest that's not a great source of evidence?
If I understand you correctly, you believe HPA-axis dysfunction causes the symptoms of CFS, which is prolonged by "factors such as mental attitude and negative feedback". Change your mental attitude and you stop the negative feedback loop, allowing recovery to occur.
This theory appears to me to be:
- Based on many unproven assumptions and leaps of logic around HPA-axis involvement.
- Based on inherently biased recovery reports that could be due to spontaneous recovery (which you mention) as much as anything.
- Results in an unfalsifiable theory that blames patients for their continued suffering (people can recover if they change their attitude/lifestyle; if they don't, they mustn't have changed their attitude/lifestyle).
This is not scientific. Theories around HPA-axis involvement are a dime a dozen. Theories around changing your lifestyle/attitude resulting in a "cure" are simplistic and patronising to the many, many sufferers who have done just that, and not seen the cure you say is possible for all patients.
CFS patients get sick of this sort of thing because it seems to be the proponents of psycho-social approaches with faulty beliefs and poor logic -- not the patients -- that leads to unfalsifiable, unscientific theories being promoted to very sick, very vulnerable people, who you say could be cured, if only they stopped with their gosh darn negative attitudes and poor lifestyle choices!
You need better evidence than anecdotes from mass media and a hand-wavvy physiological/psychological explanation to make such grandiose claims.
Please consider re-evaluating your own beliefs in light of the much broader evidence. For example, a positive attitude and lifestyle change are the driving forces for many CFS patients that leads them on decade+ journeys attempting to right the ship, only to find improvement fleeting at best.
While some people may spontaneously recover along the way, confusing correlation for causation, and painting a minority of psychological cases as reflective of the whole is unhelpful and, honestly, could do with a large serving of humility and more research about those that haven't recovered before you make grand claims about "recovery in all cases" based on mental attitudes and lifestyle changes.
Again, what patients need is real research from the scientific and medical establishments, not hand-savvy, victim-blaming theories from armchair internet experts.
The "hand-wavy" stuff you refer to is really just to try to explain things better to patients, however the actual theory itself (https://peerj.com/preprints/860/) should be solid. However, now that you point it out, I can see there are some sections of the website which I'll need to take a look at again.
Actually, rather than blaming victims, I'm actually saying that most patients don't really have good information about the etiology of the illness, which is what I'm attempting to address. (There is some anti-psychiatric bias as well, but that is present in the general population as well). Anyway, if you have any constructive comments I'd love to hear them (email is probably easier). Otherwise there's probably no point discussing any further.
1) We're on the same side here. I've been through the same exasperating journey as you, being infuriated at suggestions from doctors and armchair experts that I just needed to pull myself together and adopt a more positive attitude to life. I get it, it's horrible and patronising to be told that, and I totally understand you having the reactions your having in this thread.
2) You've inferred from the fact that some people recover from CFS via emotion-based treatments, that they weren't really very sick. This certainly hasn't been the case for me. My illness was very severe and debilitating, and is still not completely healed. My recovery has not been spontaneous or imagined (according to observations from those close to me), but has happened steadily over the 2-3 years I've been doing this very specific (but little-known) subconscious-emotion-based treatment, along with a sensible (not obsessive) diet, a small number of supplements, and gentle exercise. Sure, I would love it if there were just some pill I could take that would rapidly cure me, but as you point out, it doesn't exist, so I'm going with whatever I can find that helps, and what I'm doing now is remarkably effective.
3) But we (and many others) have read the books; tried the techniques; and are right where we started
I get it. I've done the same thing. Nothing worked. Until I discovered NET, then adapted it to be more effective for my own condition. I don't think it's the be-all-and-end-all, by any means. But I know it's promising, and it warrants research - yes, research that conforms to the scientific method - just as much as any pharmaceutical approach.
4) wanting real funding for real research for a real disease
It's not as if there hasn't already been a lot of research put into CFS over a long time. Could there be more? Sure. Would even an unlimited amount of pharmaceutical-focused research yield results? I strongly believe it wouldn't.
5) Physiological treatment will work alone, just like they have for stomach ulcers, and countless other illnesses that were previously attributed to vague, non-scientific explanations.
There's no reason to believe this is true. All the evidence I can see indicates that it fits more into the category of MS, MND, Alzheimer's, autism spectrum disorders and all the other illnesses (including many cancers) that have been extensively researched for years and show no signs of being any closer to being solved.
6) If I, or any other of the many sufferers out there, could heal ourselves through some emotional technique then we would be _over the moon_
If you're serious about this, you should get in touch. I don't expect you to blindly accept any of my claims and undertake the same treatment program as me. But I'm quite serious about getting some proper research done into the treatments that have been effective for me and others I know.
So if you'd like to know more, or contribute in some way, even as a well-meaning naysayer, feel free to drop me a line - tom.howard/gmail.
But, if you want something more real, how about cancer pain? Many people experiencing cancer pain experience relief from that pain with the help of the treatment you ignorantly dismiss as "self help emotional woo".
Everyone knew that there were multiple contributing risk factors, including physiological, behavioral, and stress-related, for gastric ulcers before H. Pylori's contribution was discovered. And all those other factors are still relevant after H. Pylori, too, its just one added factor that wasn't known previously.
A lot of CFS patients bring up the subject of stomach ulcers. It's almost as if they want to prove that psychosomatic illness doesn't exist.
It feels so weird to separate the psychological and physiological so cleanly. It seems obvious psychological stresses can damage someone physiologically over time, and vis versa. Otherwise you are making a claim that 'mind' and 'body' are separate, an outdated viewpoint originating in ancient times when everyone believed in the soul.
It just seems that having a certain type of prolonged psychological outlook (say, being stressed to death because of school, work, social pressures, existential angst, etc.) can cause serious, and 'real' physical issues and imbalances, enough for doctors to label something as a syndrome.
A psychosomatic diagnosis is often a cop out when your illness doesn't fall within the confines of a doctor's knowledge. You should never take such a diagnosis at face value.
There is so much we don't know about the impact of viruses & microbes on our immune system.
Well, this is the worst possible interpretation of my point, or whatever they call that in debate circles. I never said all physical ailments have a psychological basis, obviously a virus doesn't, just some of them very well could.
I think it's crazy as well as ignores a lot of evidence out there to rule out all physical ailments from having a psychological basis. A scenario often cited towards this is the plunge in life expectancy across the board following the collapse of communism in ex-communist states, due to tremendous amounts of stress from a forced change in your way of life. Clearly psychological dimensions can affect your physical health and balance of systems in your body.
I agree that such a diagnosis should only be a last resort, but I disagree that it should never be considered a valid diagnosis.
From this experience, here are my thoughts:
- I do believe its primary cause is psychological, but it's symptoms are real, physical and profound.
- I do believe it should be taken very seriously by mainstream medicine.
- I believe it can be cured, but not by focusing exclusively on physical symptoms, or through any treatments currently offered by conventional mental health professionals.
The best progress I've made in overcoming the condition is through a non-medical treatment to identify and correct subconscious traumas and self-sabotaging beliefs. The closest thing in mainstream medicine is CBT, but what I'm doing seems far more effective.
On the physical side, there is an obvious inflammatory immune response going on. I'm allergic to just about everything. I have IBS, I have GERD.
On the psychological side, this inflammation causes a constant sense of panic. The symptoms of the anxiety cause muscle tenseness and lead to further inflammation. The adrenaline causes me to be tired after low levels of exertion.
I've learned to manage the anxiety through mindfulness and CBT (some days are better than others) but the chronic inflammation is still there.
So, while I agree with you that there is a psychological component and that treating it helps CFS sufferers to cope, I think it's a chicken-and-egg argument at this point about which started which. I wouldn't jump to the conclusion that it's all psychological just based on having some improvement to quality-of-life by working on your mental health.
Not that it's not worthwhile -- it definitely is -- it just probably isn't the whole 'answer".
And I don't believe the physical symptoms should go untreated; throughout my illness I've put a lot of work into alleviating physical symptoms, and continue to do so.
Indeed, I'm well aware the whole concept of "primary cause" in such a complex system as the human organism is very fuzzy.
But my experience is this: for the first few years of being ill, I focused purely on physical symptoms and undertook physical treatments; I experienced some level of improvement, but it was never profound or sustained.
Since finding a treatment that focuses on underlying emotional issues, and persisting with it over a couple of years, the improvement has been profound and sustained.
And having developed a deep understanding of the way emotional traumas can lead to physical symptoms, it now makes complete sense to me that the trauma came first, and physical stuff happened as a consequence, so to completely reverse the illness, the original trauma needs to be completely healed.
From talking to others with similar illnesses, a significant level of early life trauma seems to be a consistent factor.
I'm well aware that chiro attracts much contempt in forums like this one, and indeed I'm not in any way a devotee of chiro generally (anymore).
But I was made aware of NET when I was trying chiro as a possible treatment for my condition, and found that whilst conventional chiro didn't help much, NET helped a lot.
I've since learned how to do it myself without the help of a practitioner, so I can do it daily without having to spend the time or money visiting a clinic.
I've also found my progress has accelerated since I started doing a particular kind of yoga called Kundalini. I now try and do that daily too.
NET is just one of many techniques for improving the subconscious mind; others include more traditional practices like meditation, hypnosis, prayer, as well as more recently-developed ones like neuro-linguistic programming and emotional freedom technique ('tapping').
But I've tried all these over many years, and NET has been by far the most effective.
CFS is not a diagnosis, it's a label for a syndrome which should only be applied after a medical practitioner has exhausted all her diagnostic capabilities without conclusive results. CFS is not something that should ever be on top of the list, it's only a fallback for when you reach the end of the list, and it has to be this way by definition.
However, these syndromes sometimes develop a life of their own. It can be because our diagnostic means still have glaring weaknesses. Or because doctors don't want to explore something any further. Or because a syndrome becomes a cultural phenomenon. This is parodied pretty well in an animated Dilbert episode with "Chronic Cubicle Syndrome".
Because of this cultural baggage (which affects physicians as well) it might be better to move away from a syndrome-based nomenclature for these things. Idiopathic Chronic Fatigue would be a much better term.
That's why I think studies on groups of patients labeled with a syndrome are net-beneficial while every patient actually "diagnosed" with CFS is a medical defeat.
Chronic fatigue triggers -> medicines (many of them are starting to be known for being cytotoxic - bacteriocidal antibiotics anyone?), surgery (plenty of well-known mito diseases are triggered by general anesthesia or exacerbated by), severe infections (energy saps of the body that can throw off the energy homeostasis greatly even in normal people).
Hell depression and anxiety may even be mitochondrial disease manifestations in the brain in some cases.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760005/
http://www.ncbi.nlm.nih.gov/pubmed/22579150/
http://www.mitoaction.org/files/Dykens%20for%20Mitoaction.pd...
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763246/
http://triggered.stanford.clockss.org/ServeContent?rft_id=in...
It's completely fucking tragic that society has to demonize mental illness and all these debilitating diseases that we are causing ourselves in many cases. It's a fucking luck of the draw whether or not it will destroy you and possibly harm your future lineage.
It makes sense that stress reduction helps some people because stress uses up a lot of energy. That's less energy for maintaining homeostasis in a weak metabolic system.
One open question is to whether it is secondary or primary mitochondrial disease.
This article reports on doctors still diagnosing people with chronic fatigue syndrome and backs up their study with actual research. But this huffington article gives no real information - it just states that the study had a control group of 358 and a test group of 298. It doesn't give any numbers other than that.
Chronic fatigue syndrome and, now, chronic Lyme disease are probably more related to depression than to any external biological agent like a virus or bacterium.
But the fact remains that the disease, a very complicated disease with no direct simple cause and no direct simple cure (let alone treatment), exists. A large part of the problem is there is little money in it, from the medical industry's perspective. Not a large enough "market" of sufferers. Not a large enough business opportunity for the pharmaceutical industry. Not a large blip on the radar of the health insurance industry who don't give a damn. Not a large enough concern for the NIH and other government agencies. And so the money doesn't flow. And that means a lot of research doesn't get done. And CFS/ME stays on the "fringe", and a lot of mainstream doctors in Kaiser and other big systems don't know how to or don't want to deal with CFS/ME, because it doesn't show up on their checklists, it's too nuanced for them to bother with, and the patients are sent "out of network" (read: they're on their own).
And so it goes.
Finally, I would beg to differ regarding no viral or bacteriological signatures for CFS/ME. More than a decade and a half of direct experience with a loved one with CFS/ME suggests that there is, based on evidence shown of viral markers revealed in exotic, hard-to-get blood tests (read; insanely expensive, not-covered-by-insurance) that most labs won't even do.
As someone who has been battling something that seems to fit the description of CFS for several years, I agree with you that it is largely a psychosomatic condition, and the success I'm now seeing in overcoming it has coincided with a lot of work I've been doing to overcome emotional traumas and self-sabotaging beliefs.
That said, I have seen studies that show a correlation between CFS symptoms and active infections of several viruses including Epstein-Barre, Cytomegalovirus, and Human Herpesvirus 6.
These viruses are present in most people but dormant - whereas they are commonly found to be active in those diagnosed with CFS (along with MS, Aspergers's, Alzheimer's and other auto-immune conditions).
I was tested for EBV and CMV (HHV6 wasn't available at the lab I went to) at the time I started to feel significantly better, and was found to have evidence of previous active infections of both, but neither were active at the time of the test.
From all the research I've done, the mechanism seems to be: prolonged emotional stress/trauma -> weakened immunity and/or auto-immunity -> fatigue and illness as infections take hold and body tissue is damaged by auto-immunity.
So I guess you're right in the sense that there is no single bio-marker for CFS, but there are correlates that can help to support a diagnosis.
As for treatments, well I haven't seen any practitioners offer anything convincing. So maybe your comment was totally valid after all.
[1] http://journals.plos.org/plosone/article?id=10.1371/journal.... [2] http://www.ncbi.nlm.nih.gov/pubmed/?term=15113035 [3] http://journals.plos.org/plosone/article?id=10.1371/journal....
As someone whose partner has CFS (since she was aged 12) I have to disagree strongly on this, although my experiences are anecdotal I'm more than 99% sure CFS is a physical condition rather than mental.
Having also studied much of the scientific literature of the past few years I'd be strongly critical of your assertion based on the results of any respected doctor or controlled study.
Unfortunately suggesting it's a mental condition has resulted in such helpful suggestions from doctors as "get a new hair cut to cheer you up" which is akin to telling a cancer sufferer that lipstick might help.
I'd be happy to discuss further and provide numerous studies suggesting it is a result of a (most likely) viral infection that has had long term repercussions on the immune system.
There are scammers out there, but it's not the patients or the majority of doctors - at least in the UK.
Disclaimer: I'm currently working on a data gathering problem related to this as a side project with a view to crowdsourced funding.
I think you've hit the nub of the problem with your statement that you're "more than 99% sure CFS is a physical condition". The majority of people (including many doctors) simply don't understand certain basic facts about how the body works (such as the fact that cortisol is a stress hormone, but also one of the main modulators of the immune system). Most people still have a Cartesian/Victorian view of the human body, and believe that the mind and body are completely separate.
Telling someone to "get a new hair cut to cheer you up" won't be much use for major depression or PTSD either. Comments like this just perpetuate the misconception/prejudice that psychiatric conditions aren't real illnesses. I think it's a combination of this prejudice, combined with a misunderstanding of how the body works, that has caused most of the problems relating to understanding CFS.
I'm always open to differing views, so would be interested in any recent papers pointing to a psychosomatic cause, especially as this seems to be an area active research is moving away from.
I completely agree the mind/body need to be treated more as a single entity, but the researchers and clinicians I've been engaged with are most certainly looking at this in a non Cartesian way. Nb these are not general practice doctors.
Again, I'm comp sci rather than medical, so my experiences are anecdotal but a good many of the CFS patients I've known have not been under chronic stress with the often exception of CFS seemingly being triggered by a viral infection such as glandular fever. I can't comment on whether cortisol levels remain high.
Fundamentally there is so much we don't understand about what may in fact be a group of illnesses, hence why people's personal stories seem to fall into two or three conflicting camps.
We need more data to go on, which is why I've a side project looking to address this which will hopefully lead to more areas of research.
Studies do show that the majority of CFS patients report more stressful life events preceding their illness than controls (e.g. Salit 1997, Hatcher et al. 2003, Theorell et al. 1999). Also, from speaking to patients, you do very often find that they lived stressful lives prior to developing CFS.
Also bear in mind that it may be burnout more than stress that is important in triggering the illness, and it appears to be possible to have burnout even in the absence of stress (see for example Pruessner et al., 1999).
Infections also activate the HPA axis in a similar way to psychogolical stress, and it may be a combination of stress and infection that causes CFS. (Some studies show that gulf war syndrome is more likely if vaccinations occur during the stress of combat). Alternatively the viral infection at onset might simply be due to suppression of the immune system due to stress.
If you're interested, here is my theory of CFS:
https://peerj.com/preprints/860/
Feel free to email me or leave a comment there if you have any comments. If you're interested in this area, I'd recommend reading the full-text of the studies in my references -- let me know if you want the full-text of any of them. Like you I'm compsci rather than medical, but IMO a lot of the medical people aren't really doing a good job at figuring out this illness.
I saw in one place that your your understanding of the illness was described as "6 months of disabling fatigue, depression, sleep disturbances, and/or GI problems"
If that's the case then I'm afraid I don't think you are really an authority to talk about CFS from the perspective of a former patient. That does sound like a stress related breakdown which happens to share many of the symptoms associated with CFS.
Maybe I misunderstood but it seemed as though you were drawing a line between mental and physical origins of the disease and I just don't see how this is so "highly likely" or even a useful distinction.
That said I think it is highly likely that we simply don't understand enough about the brain or body to say one way or another what could be causing diseases like CFS.
Certainly, it's possible for the brain and body to influence each other. Any severe infection will induce "sickness behaviour" for example, causing symptoms like fatigue and depression -- very similar to CFS in fact. However there is quite significant evidence that is caused by a dysregulation of the stress system, and not really much if any evidence showing an infectious etiology. Pretty much all the pathophysiology is consistent with a stress related illness, including this interferon-gamma biomarker.