Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome, Norcliffe-Kaufmann et al, 2022

[cassava7]

Despite its increasing recognition and extensive research, there is no unifying hypothesis on the pathophysiology of the postural tachycardia syndrome.

In this cross-sectional study, we examined the role of fear conditioning and its association with tachycardia and cerebral hypoperfusion upon standing in 28 patients with postural tachycardia syndrome (31 ± 12 years old, 25 women) and 21 matched controls.

We found that patients had higher somatic vigilance (p = 0.0167) and more anxiety (p < 0.0001). They also had a more pronounced anticipatory tachycardia right before assuming the upright position in a tilt-table test (p = 0.015), a physiologic indicator of fear conditioning to orthostasis.

While standing, patients had faster heart rate (p < 0.001), higher plasma catecholamine levels (p = 0.020), lower end-tidal CO2 (p = 0.005), and reduced middle cerebral artery blood flow velocity (p = 0.002).

Multi-linear logistic regression modeling showed that both epinephrine secretion and excessive somatic vigilance predicted the magnitude of the tachycardia and the hyperventilation.

These findings suggest that the postural tachycardia syndrome is a functional psychogenic disorder in which standing may acquire a frightful quality, so that even when experienced alone, it elicits a fearful conditioned response. Heightened somatic anxiety is associated with and may predispose to a fear-conditioned hyperadrenergic state when standing. Our results have therapeutic implications.

https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awac249/6634171

 

[Midnattsol]

...

 

[Amw66]

Despite its increasing recognition and extensive research, there is no unifying hypothesis on the pathophysiology of the postural tachycardia syndrome.

In this cross-sectional study, we examined the role of fear conditioning and its association with tachycardia and cerebral hypoperfusion upon standing in 28 patients with postural tachycardia syndrome (31 ± 12 years old, 25 women) and 21 matched controls.

We found that patients had higher somatic vigilance (p = 0.0167) and more anxiety (p < 0.0001). They also had a more pronounced anticipatory tachycardia right before assuming the upright position in a tilt-table test (p = 0.015), a physiologic indicator of fear conditioning to orthostasis.

While standing, patients had faster heart rate (p < 0.001), higher plasma catecholamine levels (p = 0.020), lower end-tidal CO2 (p = 0.005), and reduced middle cerebral artery blood flow velocity (p = 0.002).

Multi-linear logistic regression modeling showed that both epinephrine secretion and excessive somatic vigilance predicted the magnitude of the tachycardia and the hyperventilation.

These findings suggest that the postural tachycardia syndrome is a functional psychogenic disorder in which standing may acquire a frightful quality, so that even when experienced alone, it elicits a fearful conditioned response. Heightened somatic anxiety is associated with and may predispose to a fear-conditioned hyperadrenergic state when standing. Our results have therapeutic implications.

https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awac249/6634171

Someone let Dr Blitshteyn know
She's already batted back at Stone .

 

[Peter T]

I had been suffering adverse effects of orthostatic intolerance for several years before I even knew orthostatic intolerance existed. Once I was aware it was a possibility and offered an explanation for some of the variation in my ME symptoms, I was better able to manage my activity and this reduced the negative impact of my orthostatic intolerance.

I believe that conscious awareness of orthostatic issues if anything reduced anxiety for me as it enabled me to avoid negative consequences, for example I could avoid fainting when taking the cat to the vets by insisting a chair was brought into the consultation room so I could sit down and I did not feel awkward about this because I had rational explanation to give for it.

 

[Hutan]

Your alexithymia* is showing @Peter Trewhitt

* alexithymia (PSYCHIATRY): the inability to recognize or describe one's own emotions.

You didn't realise how afraid of standing you were.

()

These findings suggest that the postural tachycardia syndrome is a functional psychogenic disorder in which standing may acquire a frightful quality

Absolutely incredible. And so the variability from one day to the next is because some days we are easy frightened and other days we are braver?

 

[ME/CFS Skeptic]

Anyone have access to the paper? Interested in how they measured 'somatic vigilance'.

These findings suggest that the postural tachycardia syndrome is a functional psychogenic disorder in which standing may acquire a frightful quality, so that even when experienced alone, it elicits a fearful conditioned response.

So they select patients for having symptoms while standing up and others who don't. Then they let them stand up for a while and notice that the first group is more tensed, anxious or has a higher heart rate before standing.

All these things are to be expected within any ethiological theory about POTS. They would likely happen if POTS was and if it was not a functional psychogenic disorder. So their data have nothing to the with the hypothesis they fancy.

 

[ME/CFS Skeptic]

I wonder if studies like these ever get criticised by proponents of a psychogenic theory. Suppose you believe in such an explanation for POTS, you would be rather annoyed by studies like these that make overstatements and whose experiments have little to no relevance to the hypothesis in question.

Yet one hardly sees criticism within the psychosomatic literature. They all seem to like anything that suggests a psychosomatic cause.

 

[cassava7]

So they select patients for having symptoms while standing up and others who don't. Then they let them stand up for a while and notice that the first group is more tensed, anxious or has a higher heart rate before standing.

All these things are to be expected within any ethiological theory about POTS. They would likely happen if POTS was and if it was not a functional psychogenic disorder. So their data have nothing to the with the hypothesis they fancy.

A relevant comparison:

“Anyone who reacts to bee stings with anaphylactic shocks and has already experienced this will also react more strongly to the observation of another sting. However, this does not make the allergic reaction psychosomatic.”

 

[Midnattsol]

I wonder if studies like these ever get criticised by proponents of a psychogenic theory. Suppose you believe in such an explanation for POTS, you would be rather annoyed by studies like these that make overstatements and whose experiments have little to no relevance to the hypothesis in question.

Yet one hardly sees criticism within the psychosomatic literature. They all seem to like anything that suggests a psychosomatic cause.

We can't forget that it can be difficult to get criticism published.

A recent example from Norway: Some years ago researchers found that having to have a meeting with the disability and welfare office, employer etc made people have shorter sick leaves. This study, that used registry data and had no way of knowing who had been asked to attend such meetings or not, was published in a high impact journal. Recently the same researhers performed an RCT where people on sick leave where either asked to attend such a meeting or not, and they found that the meeting didn't have anything to do with the length of sick leave after all. This new, higher quality study, was much harder to get published.

 

[Ebb Tide]

I wonder what tools the authors used to measure anxiety/fear conditioning and whether they referenced this paper.

The researchers of the paper below included Dr Raj who is on the medical advisory board of Dysautonomia International and the first author is his wife who is a psychiatrist.

They found that anxiety appeared greater when questionnaires measuring anxiety included core physical symptoms of POTs rather than when using tools looking at the cognitive features of anxiety, which showed they had no more anxiety than the general population.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758320/?tool=pubmed

 

[ME/CFS Skeptic]

If I understand correctly they used this scale, as defined in this paper from 1997:

Schmidt NB, Lerew DR, Trakowski JH. Body vigilance in panic disorder: evaluating attention to bodily perturbations. Journal of consulting and clinical psychology. Apr 5 1997;65(2):214-20.​

 

[ME/CFS Skeptic]

If I understand correctly the score of item 3 is divided by 10 and for item 4 an average for all 15 symptoms is made so that all 4 items have a 0-10 scale and these are then added to a total score (0-40).

In this study, patients scored an average of 24 while the controls had a score of 17. In the paper the authors write that patients were "paying greater attention to surveying bodily sensations of chest discomfort and symptoms of hyperventilation (breathing, numbness, tingling, dizziness) - all features reported to determine susceptibility to fear conditioning."

Perhaps this was simply because patients had these symptoms while controls didn't?

 

[ME/CFS Skeptic]

I think these papers would be taken less seriously if they were required to add the questionnaires they used...

 

[Arnie Pye]

Referring to the scoring questionnaire in post #11, some of the "sensations" they ask about are things that we are told we must always take seriously e.g. chest pain and choking/throat closing. When and why does it become a stick to beat the patients over the head with?

 

[cassava7]

If I understand correctly they used this scale, as defined in this paper from 1997:

Schmidt NB, Lerew DR, Trakowski JH. Body vigilance in panic disorder: evaluating attention to bodily perturbations. Journal of consulting and clinical psychology. Apr 5 1997;65(2):214-20.​

View attachment 17627

All of the symptoms in questions 3 and 4 can arise from orthostatic intolerance. This questionnaire simply cannot be validated for use in patients with POTS. Perhaps if the authors had looked at questionnaires validated for use in POTS like COMPASS-31, or were simply more informed about the symptoms of POTS, they would have realized that this questionnaire is unfit for purpose.

However, it is reasonable to assume that researchers who have study participants undergo the standard diagnostic test for a condition with extra measurements — tilt test with measurement of cerebral blood flow velocity — would be knowledgeable on the symptoms of that condition. I am definitely not sure that we can put their interpretation of the results down to incompetence alone…

 

[Hutan]

To summarise, from the abstract and the points made above:

We found that patients had higher somatic vigilance (p = 0.0167)

They found that people who have POTS symptoms, including potentially falling over if they don't sit down when feeling faint, think about their body sensations more than people who don't regularly have such symptoms.

and more anxiety (p < 0.0001).

They found that the people who have POTS symptoms have POTS symptoms - these symptoms can give the appearance of anxiety on questionnaires.

They also had a more pronounced anticipatory tachycardia right before assuming the upright position in a tilt-table test (p = 0.015), a physiologic indicator of fear conditioning to orthostasis.

They found that people who rightfully expected the tilt table test to be an unpleasant experience had higher heart rates prior to the tilt test - a normal response to rational fear.
Also, perhaps the increased heart rate of the people with POTS, can be at least partly attributed to the orthostatic and exertional challenge of coming into the clinic, and waiting to undergo the test.

While standing, patients had faster heart rate (p < 0.001), higher plasma catecholamine levels (p = 0.020), lower end-tidal CO2 (p = 0.005), and reduced middle cerebral artery blood flow velocity (p = 0.002).

They found that when standing, people with POTS have POTS symptoms, but healthy people do not.

 

[MSEsperanza]

While standing, patients had faster heart rate (p < 0.001), higher plasma catecholamine levels (p = 0.020), lower end-tidal CO2 (p = 0.005), and reduced middle cerebral artery blood flow velocity (p = 0.002).

Multi-linear logistic regression modeling showed that both epinephrine secretion and excessive somatic vigilance predicted the magnitude of the tachycardia and the hyperventilation.

In the paper the authors write that patients were "paying greater attention to surveying bodily sensations of chest discomfort and symptoms of hyperventilation (breathing, numbness, tingling, dizziness) - all features reported to determine susceptibility to fear conditioning."

So did they acually measure hyperventilation as implied in the first quote / do the mentioned parameters reliable measure hyperventilation?

Or is this statement just an inference from the answers to the questionnaire, that is about some symptoms that occur with hyperventilation but can also occur without hyperventilating ?

 

[Charles B.]

Patients forced to touch a scalding pot of water exhibited greater anxiety than controls. Therefore, we conclude the resulting first degree burns are merely an extreme behavioral response that can be addressed through bespoke CBT.

these logical fallacies don’t pass the laugh test. I don’t understand how people don’t kick these charlatans out of the profession. My guess is that the broader medical establishment feels these conditions don’t warrant legitimate research and should be de-medicalized. Thus, there is absolutely no scrutiny or oversight.

 

[rvallee]

It's studies like this that will be remembered once this nonsense is trashed in the same bin as phrenology. Studies so dumb you can't even imagine anyone in academia could manage to produce it, but then you actually realize that this stuff is beloved, popular, praised!

It truly reveals the lie that is at the core of so-called evidence-based medicine: you can literally argue anything out of anything and it doesn't matter if it's true or not, as long as it's popular it will be popular. It's all associative, so if you can show that Nicolas Cage movies associate with pool drownings, than as long as people generally love the idea of this association, you can claim it, it will be published, and people will drool and gush over it, no matter how obviously ridiculous it is.

The corollary of this is a simple but demoralizing:

1. If it's wrong and popular, it will be popular
2. If it's right and unpopular, it will be unpopular

Evidence-based medicine needs to be ended. It's become a blight on medicine, essentially acting as a capstone on the discipline. It's no longer possible to find new things because if it's new, people will point at the textbook and say: "not in the textbook, has to be false".

Medicine is no longer science-based. Alternative medicine has become the new default, and it's popular, which is all that matters here. Incredible, it's so much like how Idiocracy envisioned it, the differences are frankly irrelevant.

 

[rvallee]

Truly astounding thinking about the "logic". It equates epinephrine, literally the way the cardiovascular system works, as a "fear" hormone. Even though it's just the basic function of how the nervous system works. So I guess that coffee is basically liquid fear, or whatever.

By extension of this nonsense, it would also make Parkinson's disease a functional whatever, since everyone knows dopamine is the happy hormone, therefore it must mean they are depressed. Deal with the depression, increase dopamine, and you fix the mood disorder.

This biopsychosocial nonsense is incredible. Reducing complex systems to convenient simplified ideas, equating multifunction hormones in a complex system to a simple idea. It basically equates basic biological functions with moods. Honestly, we just traded the humours for the moods. This is an extension of the same inability to think.

I'm gonna call this ideology The Moods from now on, as a direct reference to the humours, which this basically is.