Immune network analysis of cerebrospinal fluid in ME/CFS with atypical & classical presentations

[ljimbo423]

"This cytokine panel was developed as an assay for investigating acute phase (sickness) responses and neuroimmune dysregulation in neuropsychiatric disorders..."

Two questions I'm grappling with: First, why is this panel being applied to ME/CFS sufferers?

It would be the neuro-inflammatory connection wouldn't it?

 

[duncan]

@ljimbo423 , that would help explain it for acute conditions, which ME/CFS usually (at least by current definition) is not. Also, it seems to me this would preclude encephalitis and similar neurological inflammatory conditions. The focus seems somehow askew.

The focus could be interpreted to be psych-centric. The journal of choice doesn't help calm my concerns.

 

[barbc56]

All very interesting points. Have there been studies that compare these tests with a healthy population?

Edit. I agree there are better places than where this study was published. Buzzwords that may be misinterpreted in a negative sense.

 

[alex3619]

I don't think there is a major concern that this chip was developed for neuroimmune disorders. Isn't that what we have been saying ME is all along? The choice of publication might first appear odd, but this is what Google came up with -

Translational Psychiatry is a sister journal to the well-established journal in psychiatry, Molecular Psychiatry *, but explores the translational pathway between research in neuroscience and conceptually novel treatments.

This is biopsych at worst, not psychopsych, and at best represents a shift to neuroimmune biochemistry.

The only potential concern here is that many papers may be published, and I have not confirmed this, that are about trying to validate psychopsych theories.

When the biology of psychiatric conditions becomes well established they tend to move to other disciplines, especially neurology, and in this case neuroimmunology might be more appropriate.

 

[duncan]

@alex3619, agreed, but we are not there yet. What you are talking about could take many years. So the data set - hell, the assay itself - could be used by some against us. This is what I was referring to earlier when I spoke of who could hijack this data. Also, the paper doesn't just say neuroimmune dysfunction - it relegates neuroimmune dysfunction specific to neuropsychiatric disorders.

Easy solution: How does our profile generated by this assay stack up against commonly recognized neuropsychiatric disorders. Downside to this, potentially, is if there are similarities in the profiles, we just got jettisoned back by who knows how much.

It's kind of like in a court of law, that old legal adage - never ask a question you don't know the answer to.

 

[Diwi9]

@duncan - I get your concern, especially in the short term, but this is biologically based science. MS has neuropsychological symptoms too. We have serious issues with cognitive dysfunction. My guess is that most psychiatric conditions will be stolen from psychiatry as the biological bases of "mental disorders" are fully explored.

 

[Rooney]

Dr. Hornig's info is below.
She is perfectly suited to study our disease. I'm thrilled she is on our team. Wonderful advocate. I believe she is a neurophychiatrist, thus the publication in this journal.
mh2092_3_Mady_Hornig2.jpg

Mady Hornig
Associate Professor
Epidemiology (in the Center for Infection and Immunity) at the Columbia University Medical Center
Office/Address:
722 W 168th St, Rm 1801
New York 10032
Phone:
212-342-9036
Fax:
212-342-9044
Website address:
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Email:
mh2092@columbia.edu
Biography Topics Education Mailman Affiliations Editorial Boards Columbia Affiliations Academic Appointments Other Affiliations Honors & Awards Areas of Expertise Select Urban Health Activities Select Global Activities Select Publications Back to Top
Biography
Mady Hornig, MD, MA, is Associate Professor of Epidemiology and Director of Translational Research in the Jerome L. and Dawn Greene Infectious Disease Laboratory at the Mailman School of Public Health, Columbia University. A physician-scientist, she is widely recognized for her animal model and clinical research on the role of microbial, immune, and toxicologic factors in neuropsychiatric disorders, including autism, schizophrenia, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and mood disorders.

 

[duncan]

My guess is that most psychiatric conditions will be stolen from psychiatry as the biological bases of "mental disorders" are fully explored.

Well, sure. Eventually. But right now, you give me two psychiatrists who publicly decry Cartesian Dualism, and I will give you two back that speak it fluently amongst themselves.

There is where we should be, and where we are. Where we are, imo, is NOT embracing assay panels that are designed for conditions that don't represent us. This assay panel is for acute conditions - that ain't us. As for the neuropsyciatric disorder utility - this is precisely the label we have labored so long and so hard to escape - and these people are using an assay for these very disorders??

I cannot subscribe to that logic. Pick another assay panel. Or contrive one.

 

[duncan]

he is widely recognized for her animal model and clinical research on the role of microbial, immune, and toxicologic factors in neuropsychiatric disorders, including autism, schizophrenia, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and mood disorders.

Cool. Add ME/CFS to that list.

 

[Diwi9]

@duncan - They will create unique assay panels down the road, I believe. This is a dedicated team and as other posts in the thread have mentioned, this is really just a pilot to seed future funding sources.

 

[Jonathan Edwards]

@Jonathan Edwards Has anybody activated you for an expert opinion?

I rather agree with A.B. This paper is hard to understand.

I find the analysis of clusters of results hard to grasp. I am afraid I am used to more black and white differences. I appreciate that to get at the real biology it may be necessary to use this sort of fine toothed comb but it is hard going.

I see no problem with the choice of journal or the panel of assays. I suspect that tailored for neuropsychiatric conditions means tailored to things like Parkinson's Disease and other problems causing brain malfunction through cytokine pathways. Much of many Hornig's previous experience is with post-streptococcal brain disorders. And after all neuroborreliosis would be considered slam dunk in the middle of 'neuropsychiatric disorders'.

 

[duncan]

And after all neuroborreliosis would be considered slam dunk in the middle of 'neuropsychiatric disorders'.

LOL. Why do I get the sense that was intended for me?

Who would treat neuroborreliosis when the infectious disease specialist falls flat? I will volunteer that: Neurologists, not neuropsychs, at least as a rule.

Would you consider Lyme Encephalomyelitis a neuropsych disease? Again. this is the domain of the neurologist, certainly in difficult cases. Psychs are involved only peripherally, if at all, same as with cases of brain tumors.

Perhaps there are lessons to be gleaned here.

 

[duncan]

I suspect that tailored for neuropsychiatric conditions means tailored to things like Parkinson's Disease and other problems causing brain malfunction through cytokine pathways.

You may be right. It would be good, though, to confirm. I would still like to know how we compare with that assay panel to neuropsych disorders listed in her bio.

 

[Jonathan Edwards]

Would you consider Lyme Encephalomyelitis a neuropsych disease?

I think you have the wrong end of the stick Duncan. We are not talking of neuropsychiatric diseases. We are talking of neuropsychiatry, which is the study of the biomedical basis of brain disorders presenting with abnormal higher mental function - brain fog, fatigue, memory loss, or whatever. Those conditions may also present with localising signs. So Lyme Encephalomyelitis comes under neuropsychiatry just like B12 deficiency can, or lupus, or sever hypothyroidism or Cushing's syndrome.

Perhaps the key point is that you only call it neuropsychiatry rather than psychiatry because the assumption is that the is some physical inflammatory, endocrine, or other physiological basis underlying the symptoms. You do not call depression or schizophrenia neuropsychiatry - unless as someone suggested you have already taken the step of assuming that you are dealing with a biological process other than having an over dominant mother or a repressed oedipus complex or whatever. Many Hornig's interest in these conditions is purely in terms of neuroinflammatory diseases.

 

[alex3619]

But right now, you give me two psychiatrists who publicly decry Cartesian Dualism, and I will give you two back that speak it fluently amongst themselves.

Most anti-dualists are, in my opinion, closet pro-dualist. Unless they clearly stand up as monists then dualism, acknowledged or not, needs to be considered. Indeed this is sometimes a particularly problematic form of dualism - mind and body are one, you cannot separate them, but mind is more important. They almost never discuss physical problems causing psychiatric symptoms, or the abysmal history of failure in psychogenic medicine.

 

[duncan]

We are talking of neuropsychiatry, which is the study of the biomedical basis of brain disorders presenting with abnormal higher mental function - brain fog, fatigue, memory loss, or whatever.

By your rather encompassing definition, brain cancer would be included under the umbrella of neuropsychiatry, as would some channelopathies that influence cognitive function. I have seen both in action first hand, and I can vouch that both were dealt with by neurologists.

I suspect the assay panel employed in this study would be shunned in both of my examples - as I can guarantee it also would in NB.

I guess most neuropsychs would agree with your liberal definition of what the discipline should encompass. I would imagine there are many neurologists and infectious disease specialists that would limit those claims.

 

[hixxy]

Damn and blast, you've thwarted my hypothesis

I'm atypical presentation and haven't had a cold in nearly 8 years either. My illness is very much progressive too.

 

[hixxy]

Ongoing studies at CII are exploring other subgroups, including patients with allergic disorders, high levels of cognitive dysfunction, and gastrointestinal disturbances.

I haven't read the paper but does the paper say if the 2 subgroups encompass all patients and they will be further broken down into these other subgroups or are these other subgroups patients who didn't match the original 2 subgroups immune signature wise? I also wonder how many patients aren't falling into these 2 subgroups.

 

[Murph]

To our resident experts...can we align Fluge & Mella's responders along the classical and atypical subsets?

Relax, looks like the norwegians have everybody covered.

This table is from the Phase II rituximab paper and the list has the top responders at the top. Atypical onset seems well represented.

There may be links between the papers but they're not at the simple level of "Fluge+Mella only cured typical/atypical."

 

[Murph]

This journal is

a) owned by Nature
b) online & open access
c) "explores the translational pathway between research in neuroscience and conceptually novel treatments."

So it is high profile, high impact, and does serious biology. I'm super excited to see the paper in it.

Given immune responses are likely to be neurologically mediated and the word encephalitis (inflammation of the brain) is in the name of the damn disease, i reckon getting good neuroscientists excited is a terrific idea.

I will say one bad thing about this paper: In the .pdf version, the font is tiny and the lack of paragraph breaks is obscene. *Strongly* reminds me of trying to make a school assignment fit the page limit!!