Did the "Keep Psychiatry Out of the NIH Study On ME/CFS" Help or Hurt?

[Andrew]

I do understand the stance here, however I feel it is reflective of the profound stimatization of "mental" illness in our culture: including the medical community.

The fact is that all "mental" disorders are in fact neurological and physiological. Each might have multiple causes, though none are the result of "willpower," or some sort of moral failure. The artificial dichotomy, between obsolete notions of "psychiatric" and "physiological" conditions, is ruling this discussion....I know why, and I understand its political implications, but it is a false dichotomy none-the-less.

My own story is an anecdotal case in point. To keep it short: I am depressed, I have severe dysautonomia, confirmed by small fiber biopsies and cardiac testing, and I am a former athlete who is now deconditioned. I feel all these symptoms might be traced to medication that proved to be neurotoxic, and all have made me disabled and bedbound for a year now. (I have not yet been offered a diagnosis of ME...but I'm here because I feel I could.)

I also have a history of trauma (which let's face it, is far more common among those with ME and fibromyalgia, than the general population). A history of trauma is known to have strong physiological repercussions. All of these "bio-behavioral" factors might be coalescing in my case, causing a profound physiological response. (As noted, I do consider depression to be physiological). I also stress this is one case....it does not speak to others' stories, although I'm sure its complexity is shared.

Just this week I had my neurologist do a blood draw to analyze whether specific inflammatory cytokines might be causing my depression, small fiber neuropathy, and my "sickness response." This has shown to be the case in trials...and it took much research on my part to get my neurologist to buy into this hypothesis.

So, I just would like those who shudder at the idea that ME might have what are commonly called "psychiatric" (among many) causes to think about what stereotypes might underlie their reactions. My personal view is ME is an umbrella term, much like "dysautonomia," that now covers a myriad of causes and consequences: including those now unfortunately (mis)labeled as psychiatric in origin.

To understand, and more importantly, successfully treat ME, might take a more open look at what factors and conditions comprise it. My great wish is to remove stigma and bias from the discussion and investigative approach of researchers and sufferers alike.

Nothing short of Brilliant.

I'm not after an answer that sits well with me. I'm after an answer. Period. I don't care whether it's to do with gut bacteria, neurology or psychiatry.

You can't find the truth by entering a discovery process with emotionally driven biases and predispositions.

All avenues should be fully and equally explored or the whole process is pointless.


I'm tired of people deciding what the answer should be based on what agrees with them. I.E It can't be Pace, or it can't be psychological. But for some reason if it involves taking medication then it's a perfectly good solution. I can understand why normal people dismiss CFS as psychological when sufferers try so hard to shutdown anyone that mentions ownership or hard work as a solution. (Not saying that is the solution, or that it's possible, just to be open minded and not be emotional).

 

[laureano]

sorry but I don´t really have the srenght to read so much, what is this NHI study in a nutshell? where an I find more info? thanks!

 

[Cort]

sorry but I don´t really have the srenght to read so much, what is this NHI study in a nutshell? where an I find more info? thanks!

No problem Laureano - I should have included a link:
Nath Digs Deeper Into Big NIH ME/CFS Study: Warns of Push Back

 

[Cort]

I'm just saying that things can change rapidly when the right authority comes to the wrong conclusions. I think the ice we're on is thinner than we think. Look at what happened in the UK, in the beginning there was a strong biomedical approach that was completely reversed in a very short amount of time. I'm not very convinced by the "can't happen here" attitudes.

There's a whole cadre of people out there that very much want to redefine our disease out of existence and their narrative very much matches what people like Brian Walitt are saying.


Given the lessons we've learned from the PACE trial, yes it would be very wise to do so.

Let's hope it all works out. I think we can expect with near certainty some things from this study

• NK cell functioning problems
• Autonomic nervous system problems
• VO2 max problems in some patients

We'll see about the rest of it!

 

[weyland]

NK cell functioning problems

There was no specific or general mention that this type of assay would be performed according to what we've seen so far from Dr. Nath. Correct me if I'm wrong.

Autonomic nervous system problems

Two members of the present NIH study, Carine Maurer and Mark Hallett, have found autonomic nervous system problems (low HRV, same as in CFS) in functional movement disorder patients. Their assumption appears to be that they attribute these autonomic changes to psychological stress.

VO2 max problems in some patients

I don't think there has been any indication that they intend to specifically look at VO2 max as in the 2 day CPET protocol. What they've said is that they want to make patients "tired" and look at their immune profile before and after.

Thank you. Thank you for your answer. So, moving on to other questions. We have, as I said, many and we will probably take a few more. This one, we received three questions like that, it's a technical question. I have a question about, “I understand that they will be — “they” you — will be doing a two-day maximum exercise testing. But will they do the full Stevens protocol, i.e. measure the CPET-values and see if they can validate the findings of the Stevens, VanNess etc., Keller studies?

You know I'm not the world's expert on these kinds of.... My major goal here is to study neuroimmunology. And so every single aspect of it is not my goal. I just want to be able to fatigue patients and see that if before and after fatigue, is there a change in the immune profile? OK. So, that's really my goal. And so the test that we have in order to fatigue patients is going to be different. Some patients are going to get fatigued very easily, some are going to take a long [inaudible] to do it, but once they get fatigued we're going to be able to study their immune profile before and after. And so that's really my goal.

 

[Cort]

There was no specific or general mention that this type of assay would be performed according to what we've seen so far from Dr. Nath. Correct me if I'm wrong.


Two members of the present NIH study, Carine Maurer and Mark Hallett, have found autonomic nervous system problems (low HRV, same as in CFS) in functional movement disorder patients. Their assumption appears to be that they attribute these autonomic changes to psychological stress.


I don't think there has been any indication that they intend to specifically look at VO2 max as in the 2 day CPET protocol. What they've said is that they want to make patients "tired" and look at their immune profile before and after.

Can't correct you - so far as I know you're right about the NK cells; I just can't imagine that they wouldn't do that test if they are doing all those others.

Got it on the ANS and low HRV....Low HRV is a pretty common finding in chronic diseases over all, though. Of course you're right about the VO2 max. I just can't imagine that they won't measure that - although what kind of test they will do is unclear; they'll have to set some standards - have the patients meet some metabolic marker - I imagine that VO2 max will be involved but we'll. I would be shocked if they did a two-day exercise test without doing OUR two-day exercise test since we're the only ones that do that.

Of course it remains to be seen.

 

[weyland]

I would be shocked if they did a two-day exercise test without doing OUR two-day exercise test since we're the only ones that do that.

I get the sense that NIH ironically suffers from NIH (not invented here) syndrome. My impression is that this is as far as possible from a replication study. They're only interested in doing their own research in their own way to come up with their own novel findings, which they will then follow up on in phase II. This will be fine if they find something really cool and different that nobody has found yet, but if not then we probably will wish they would have done some replication instead of striking out on their own in ignorance of the evidence base.

I get the feeling that outside our little sphere nobody really finds the NK cell abnormalities or CPET results all that interesting or worth replicating. I'm actually all for these being ignored at this stage because NK cell dysfunction lacks specificity for ME and the CPET testing is too noxious to really use on patients, so we desperately need some better biomarkers.

 

[Cort]

I get the sense that NIH ironically suffers from NIH (not invented here) syndrome. My impression is that this is as far as possible from a replication study. They're only interested in doing their own research in their own way to come up with their own novel findings, which they will then follow up on in phase II. This will be fine if they find something really cool and different that nobody has found yet, but if not then we probably will wish they would have done some replication instead of striking out on their own in ignorance of the evidence base.

I get the feeling that outside our little sphere nobody really finds the NK cell abnormalities or CPET results all that interesting or worth replicating. I'm actually all for these being ignored at this stage because NK cell dysfunction lacks specificity for ME and the CPET testing is too noxious to really use on patients, so we desperately need some better biomarkers.

You're right - neither the NK cell or the CPET findings have turned on outside researchers hardly at all. I agree about CPET - it's no good at all as a biomarker but I hoped and still hope that the findings are unusual enough to attract some interest at some point.

Hopefully the Nath study will uncover some exciting stuff, reset the field and encourage other researchers to jump in.

 

[Seeksassy]

I think behavioural factors can be a contributing factor in any chronic illness, physical or mental and it is unrealistic for CFS patients to think they should not be examined to a certain extent, although not as a primary cause. I have been reading recently about Hypermobility Ehlers Danlos Syndrome and CBT is recommended to help patients manage the disease, and I have seen graded exercise therapy recommended for mitochondrial disease, two examples of obviously physical illnesses for which CBT and GET are still useful.

I think think the psychological components are a result of chronic illness, and psychological treatment can help

The petition to "Keep psychiatry out of the NIH study on ME/CFS study" is popular; it's gotten about 2,300 signatures and on the face of it, it makes sense. Who, after all, wants psychiatry in the largest NIH study ever done on chronic fatigue syndrome? I certainly don't. That's the last thing I want in a study we're hoping will help build a foundation for the next era of research into this illness.

[fright]View attachment 1421 [/fright]I question, though, whether the petition has done much good. I am not questioning the petitioners commitment to supporting people with this disease. Their commitment is clear. I am questioning some assumptions that I believe underlie the petition and the veracity of some of the statements in the petition.

The petition begins by indirectly asserting that the study creators don't recognize or are willing to use the existing biomedical research into this illness to inform the study.



P2P Mismatch?

The petition also states the study doesn't fit the P2P guidelines:



Much of the study design, however, could have come straight out of the report. In fact, in many places Dr. Nath's study goes considerably further than the P2P report proposed. The P2P report recommended that:



The Nath study:

• is doing the most comprehensive molecular profiling of immune cells ever done to date
• includes several brain imaging projects
• is measuring energy consumption in a metabolic chamber
• is growing ME/CFS neurons using stem cell technology and testing them
• is doing extensive autonomic nervous system testing
• is transplanting the immune systems of ME/CFS patients into mice
• is doing extensive viral testing
• is analyzing the gut and saliva microbiome
• is doing two-day exercise tests to assess the effects of exercise

The Executive Committee

The petition focuses on the membership of the "executive committee". It's not exactly clear what the executive committee will be doing - that is something of an area of concern. At this point they seem to be assessing whether the patients in the study meet the simple criteria for the study (infectious onset, meet the CCC, early duration patients) and giving them some initial questionnaires.

The makeup of the executive committee is not ideal but consider that the NIH was probably picking from a relatively small pool of doctors and researcher who were associated with the Clinical Center and could be on site to assess the patients.

The petition highlighted strikes against each of the members of the Executive Committee (except for Dr. Lipkin). While I understand the angst over having anyone that supports CBT/GET in the study, I question what that means.

• If a doctor or researcher says something positive about CBT does that mean that the doctor thinks the disease is psychological?
• If a doctor or researcher has included behavioral research in his portofolio, does that mean they cannot be trusted?

The petition-makers apparently think so. I'm not sure these issues - particularly in the U.S. - is that black/white.

Dr. Gill

In a 2011 NIH presentation Dr. Gill associated ME/CFS with neurasthenia (is that inaccurate?), cited findings which did not show evidence of viral infections or orthostatic intolerance, and of stating that CBT is helpful. He suggested the positive test results from unproven tests (such as viral tests) were likely to be false positive, then cites several pages of unproven treatments and ends stating that CBT/GET are the only therapies shown to provide meaningful benefit.

[fright]View attachment 1423 [/fright]He also proposed that studies elucidating the neuro-immune-endocrine study and immune gene expression could turn out to be very helpful. He stated that there is typically no history of somatic disorders such as headache and low back and that the average ME/CFS patient was typically highly functioning before they were "struck down". He also said that the depression found in ME/CFS is "secondary"; i.e. it's not a primary feature of the disease.

He advised that physicians emphasize that ME/CFS is a real illness, that it is not malingering and that it can be completely incapacitating. They should inform the patient that even though they do not know the cause of ME/CFS (or as he repeated mispelled it CSF) have good treatments for it that they can help.

There are several things in there that might really tweak one. The key question is whether the fact that a doctor supports behavioral treatments means that he believes ME/CFS is a behavioral disorder? Or could it mean that he/she's just a conservative physician?

Gill states that ME/CFS is not depression, that it is a real illness and that the medical profession simply doesn't know the cause or have good treatments for it.

A look at Dr. Gill's background suggests that psychiatry might be the last thing on his mind. Dr. Gill is an internal medicine and infectious disease specialist and his publications focus almost exclusively on the immune system.

I leave open the possibility that Dr. Gill believes CBT/GET helps, and that that belief in no way conflicts with his idea that ME/CFS is also a real and serious, physiologically based disorder. At the end of the presentation he proposed that neuro-endocrine-immune and immune gene expression studies under way might provide clues to ME/CFS.

Dr. Leorey Saligan

[fright]View attachment 1422 [/fright]Dr. Saligan is another kind of in-between figure. Saligan is exploring the "biobehavioral" aspects of cancer fatigue. He's recently found that the increased oxidative stress in red blood cells, mitochondrial issues, and the upregulation of neuroinflammatory factors contributed to fatigue in cancer. He's done numerous studies on gene expression and mitochondrial dysfunction in cancer.

With regards to post-cancer fatigue he's mostly focused on exploring the effects of HPA axis and sympathetic nervous system dysfunction on fatigue. Saligan also did a review paper on catastrophizing and cancer fatigue, and is interested in the effects of pain, sleep, depression and catastrophizing as well. It's not his main focus but he's clearly interested in that area.

Saligan has been the principal investigator of four Clinical Center studies:

• Investigating Molecular-Genetic Correlates of Fatigue Experienced by Cancer Patients Receiving Treatment (11-NR-0014)
• Molecular-Genetic Correlates of Fatigue in Cancer Patients Receiving Localized External Beam Radiation Therapy (09-NR-0088)
• Fatigue in Healthy Individuals (09-NR-0131), and
• Evaluation and Diagnosis of Potential Research Subjects with Pain and Fatigue Syndromes (08-NR-0132).

Brian Walitt

Brian Walitt has been covered before but suffice it to say that his idea that ME/CFS is a psychosomatic disorder is incredibly off-putting and the reaction to him being involved in the study is understandable.

Even Walitt, however, is not such a black/white figure. He does not believe that CBT or exercise (or drugs) are particularly helpful in fibromyalgia, and his research focus is mostly physiologically oriented. In a head-twister, he apparently wants to prove that ME/CFS and FM are physiologically based psychosomatic disorders.

Elizabeth Unger

Elizabeth Unger has done only physiological research since she took over the CDC's ME/CFS program. She has published studies on NK cell functioning, reduced telomere length, inflammatory gene expression and gynecological risk factors and has made studying ME/CFS experts and their patients a central focus. She has also archived the Toolkit and had moved CBT/GET to the management section of the document.

There's no indication that she believes ME/CFS is a psychological or behavioral disorder but Elizabeth Unger did not pass the CBT/GET litmus when she reportedly told a patient that there is scientific evidence for it - (there are dozens of studies on it after all) - so the petitioners asked that she be removed from the study.

The Committee Members

Things don't appear to be as simple in the U.S. as in the U.K. Every researcher and doctor that was linked to some sort of behavioral activity in this petition also has a strong background of physiological research.

These are not, therefore, Peter White or Simon Wessely-like figures. In fact, so far as I can tell, there are no Peter White or Wessely-like figures in positions of power in the U.S.. (Peter Manu is the last pure Wessely-like figure of note in the U.S. that I can think of, and he disappeared about 15 years ago.) The U.S. does do some behavioral research in ME/CFS, but it does much, much more physiological research, and it has for as long as I can remember.

It may be that in the past that a belief that CBT/GET may help often did indicate that a researcher or doctor had some psychological agenda but I suggest the possibility that it does not necessarily mean that today. Dozens have studies, perhaps many of them flawed, have been done on these subjects.

The more important question for me with regards to this study is what are the researchers main focus? A researcher focused on CBT/GET doesn't belong in this study and none of them are.

A Psychiatric Study

[fright]View attachment 1424 [/fright]The petition presents the study as an attempt to define ME/CFS as a psychiatric disorder. (A passage in original form of the petition - which was changed after about 1,800 people had signed it - proposed that the study would return ME/CFS research to the dark ages.)

It's clear in the "reasons for signing the petition" that's the idea the petition got across:











That's unfortunate because it deprives people with a devastating chronic illness of a legitimate source of hope.

Other Issues

In some places the petition is not accurate.



The NIH is currently funding somewhere around 10 extramural studies on ME/CFS and has been funding extramural studies (not very of them for sure) for decades. (To be more accurate, this is the first intramural study on ME/CFS done in the NIH's Clinical Center hospital.)

Two Day Exercise Tests Required For Entry



The petitioners propose that the participants do a two-day exercise test before they enter the study. Who would be willing or able, though, to tolerate two two-day exercise tests? Some people would but I imagine that most would not. A bigger question is why such a harsh requirement is necessary for a study already being filled by ME/CFS practitioners?

Another question would be whether we would even want such restrictive guidelines? Would it be better if the study results referenced the subset of ME/CFS patients who failed the two-day exercise test or if reflected short duration, infectious onset patients who meet the CCC criteria?

No Psychiatric Conditions Be Considered



If this refers to patients entering the study, then the patients will all be coming from ME/CFS experts. If it refers to psychiatric questionnaires they're a standard part of any large study. Aside from those questionnaires there are no psychiatric components in this study.

Replace Executive Committee with ME/CFS Experts (Leonard Jason, Dan Peterson, Sue Levine, Nancy Klimas, and José Montoya.)

It's a nice idea, but if the role of the Executive Committee is largely confined to checking the patients in, etc. it's simply not feasible to have outside experts be present. It's also possible that the Committee members have to come from within the Intramural Center.

It's not clear exactly what the Committee is going to do. If these ME/CFS experts can be involved, of course, it would be preferable for them to be involved.

Conclusion

The figure putting together this study - Dr. Avindra Nath - is a neuroinfectious disease specialist who has put together, not surprisingly, a study that reflects his interests. He's stated he has no background in psychiatry and no interest in it and the study reflects that.

[fright]View attachment 1425 [/fright]My conclusion is that while the intentions behind the petition were laudable that it does not help. While it certainly presents an area of concern - the presence of people who believe in CBT/GET, etc. in an important study - it ignores facts suggesting that these individuals feel ME/CFS is a real, serious physiological disorder.

From a pragmatic or strategic standpoint the petition is a failure; it has the potential to antagonize but not to effect change. After a major attempt to remove Brian Walitt failed it became clear that the NIH isn't going to budge on members with less severe problems. (There's certainly no way the NIH was ever going to remove someone like Elizabeth Unger from this study.)

The petition does reflect the belief held by many that no one who has said anything positive about CBT/GET should be allowed within ten miles of this and other studies. That's understandable but litmus tests like that may be difficult to achieve at an institution like the NIH.

The key question for me in any study is the focus of the study. If the study is focused on pathophysiology and the researchers main focus is physiology then I'm not particularly bothered by other issues. If this study had CBT/GET components, if it was focused on measuring psychiatric factors, if it had anything other than physiological elements in it that would be worth fighting for. I recognize that I'm different in that way.

In part, for better or worse, we are in the process of building relationships and gathering a community of researchers to study ME/CFS. Dr. Nath has referred to some push-back from NIH researchers who were apparently miffed by efforts to remove their colleagues. We'll never know exactly why they felt that way, but it does indicate that some researchers take attempts to knock their colleagues out of a study quite seriously.

That outcome (which no one expected) suggests that attempts to remove people from studies should be done judiciously, and only when really necessary; i.e. only when a person's ideas are so damaging and that person has such an ability to do damage, that it's worth antagonizing some people to get him/her out.

I also propose the possibility that while a belief in CBT/GET may have once been a huge red flag, and may still be a red flag, that it doesn't necessarily mean that that person believes this disease is not real or physiologically based. I believe we should put the person's history into context; i.e. determine what their main focus is - before we take action. In some cases, it might be better to just live with having some individuals in some studies.

The petition's failure to put the Committee membership into context of the whole study (it appears to play a small part in it) was, in my opinion, unfortunate. It has lead some people to have an unnecessarily dark view of a study that has the promise to move forward ME/CFS substantially.

Not sure if it helped or not. On the one hand, some doctors (like many highly trained professionals) really do not like to be questioned. On the other hand, at least they are aware that this patient population is well informed as to the possible pitfalls regarding psychiatry. For me, the psychological symptoms were a result of having chronic illness and my psychologist helped me learn how to cope with my new reality.

 

[Cort]

I think think the psychological components are a result of chronic illness, and psychological treatment can help

Not sure if it helped or not. On the one hand, some doctors (like many highly trained professionals) really do not like to be questioned. On the other hand, at least they are aware that this patient population is well informed as to the possible pitfalls regarding psychiatry. For me, the psychological symptoms were a result of having chronic illness and my psychologist helped me learn how to cope with my new reality.

Who is ready to deal with a chronic illness like ME/CFS? I sure wasn't...thirty years alter I'm still learning how!

 

[phoebe333]

Really interesting, Phoebe.

The ME/CFS community comes from a history of their disease being dismissed as not real and from a treatment background that has been absolutely dominated by two governments: the UK and the Netherlands which poured have poured millions and millions of dollars into behavioral modification treatment trials. Meanwhile proportionately little money has been spent examining other options. As a community these kinds of interventions bring all sorts of very negative connotations.

That said I think you're completely right about diseases causing all sorts of different types of symptoms. For myself, I am not depressed but the "revved uppedness of ME/CFS, the difficulty concentrating and doing things like planning ahead, etc. - those are all part of the ME/CFS world for me; this disease has physiological (inability to exercise) and psychological (difficulty settling down) manifestations - as do many diseases that effect the central nervous system do. We just need to be careful that researchers focus on the physiology.

I think given your constellation of symptoms and test results you're in the right place! Please let us know how the testing goes and good luck with your search.

Hi Cort,

I'm new, so this might have bern discussed, but I've just been reading about neuro-inflammation.... and apparently it is discernible on PET scans of people with ME/CFS. I read people who also have depression have more inflammation in the hippocampus, while people with cognitive problems, like the ones you describe, have more inflammation in the thalamus. Yet, there is overall inflammation, and it explains the disportionate rates of both conditions in ME/CFS.....along with fatigue and pain.

I'm on my reader, so I can't provide cites...but easy to Google (key words PET, neuro-inflammation, ME/CFS etc.)