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https://www.virology.ws/2022/09/24/...Y1Hh3G7eEp_mlfIRphIvEQpB5tPEMqnhdbDM5lA7aYhwA
Trial By Error: Brain Publishes Letter About Flawed Study from NYU on ‘Psychogenic POTS’
24 September 2022 by David Tuller 1 Comment
By David Tuller, DrPH
Here is David's letter: https://osf.io/9cdz5/
Response to Norcliffe-Kaufmann et al, "Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome." Brain. July 2022; online ahead of print. https://doi.org/10.1093/brain/awac249
AUTHORS
Dear Editor:
In “Fear conditioning as a pathogenic mechanism in the postural tachycardia
syndrome” (2022), the investigators document a number of associations. They report
that patients with postural tachycardia syndrome, or POTS, scored higher on anxiety
and “somatic vigilance”--that is, paying attention to bodily sensations--than controls.
They report that POTS patients, compared to controls, had a “more pronounced
anticipatory tachycardia” when alerted to a coming tilt-table test that would position
them upright. They report that, compared to controls, POTS patients positioned
upright during the tilt-table test had faster heart rate, higher plasma catecholamine
levels, lower end-tidal CO2, and reduced middle cerebral artery blood flow velocity.
The investigators explain the findings by positing that POTS patients have a “classic
Pavlovian fear conditioning” response developed after a prior episode of having
unpleasant symptoms upon standing. They describe the anticipatory tachycardia as “a
physiologic indicator of fear conditioning to orthostasis”—an assertion presumably
designed to bolster the argument that negative past experiences trigger current POTS
symptoms. At the end of the limitations section, the investigators acknowledge, as if
in passing, that they “do not know” if their findings “are a cause or a consequence of
the syndrome.” Despite this significant and obvious knowledge gap, they nonetheless
maintain that the results provide robust support for their characterization of POTS as a
“functional psychogenic disorder.”
Notwithstanding the “more pronounced anticipatory tachycardia” found in the
intervention than in the control group, a key challenge for the investigators’
hypothesis is the significant overlap between the two ranges of heart rates, as
indicated in Figure 1B. As is also clear from Figure 1B, a subset of the POTS patients,
like a subset of the healthy controls, experienced a decline rather than an increase in
heart rate in anticipation of the tilt-table test. These salient details undermine the claim
of psychogenic pathogenesis but are not addressed in the text of the paper.
Beyond that, the investigators conflate association and causation. In fact, the findings
reported here can easily be explained by assuming causality runs in the other
direction. As is common with chronic illness, many people with POTS are more likely
than healthy controls to have anxiety and to measure higher on questionnaires
assessing awareness of physical sensations. They would also be alert to factors or
conditions that could aggravate their symptoms, including a tilt table test. Many
people with POTS would therefore understandably experience a stress response upon
knowing they were about to undergo the unwelcome process of being tilted upright.
And it is not surprising that POTS patients, when in an upright position, have worse
outcomes than controls in multiple domains
The investigators are aware of the shortcomings of their data, but they nevertheless
choose to interpret the research as if it favors their hypothesis—even though it does
not. Their conclusion—that POTS 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”—is unwarranted, appears to stem from the
authors’ confirmation bias, and cannot be justified based on the results presented here.
References
Norcliffe-Kaufmann L, Palma JA, Martinez J, Camargo C, Kaufmann H. Fear
conditioning as a pathogenic mechanism in the postural tachycardia syndrome. Brain
2022; online ahead of print
David Tuller
School of Public Health, University of California, Berkeley; Berkeley, CA, USA
Svetlana Blitshteyn
Dysautonomia Clinic, Department of Neurology, University of Buffalo Jacobs School
of Medical Sciences; Buffalo, New York, USA
David Davies-Payne
Department of Radiology, Starship Children’s Hospital; Auckland, New Zealand
Brendan Delaney
Department of Medical Informatics and Decision Making, Imperial College London;
London, England, UK
Jonathan Edwards
Department of Medicine, University College London; London, England, UK
Mady Hornig, Department of Epidemiology,
Columbia University Mailman School of
Public Health; New York, NY, USA
Brian Hughes
School of Psychology, National University of Ireland, Galway; Galway, Ireland
David Putrino
Department of Rehabilitation Medicine, Icahn School of Medicine, Mt Sinai; New York
John Swartzberg
Division of Infectious Diseases and Vaccinology, University of California, Berkeley;
Berkeley, CA, US
Trial By Error: Brain Publishes Letter About Flawed Study from NYU on ‘Psychogenic POTS’
24 September 2022 by David Tuller 1 Comment
By David Tuller, DrPH
Here is David's letter: https://osf.io/9cdz5/
Response to Norcliffe-Kaufmann et al, "Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome." Brain. July 2022; online ahead of print. https://doi.org/10.1093/brain/awac249
AUTHORS
Dear Editor:
In “Fear conditioning as a pathogenic mechanism in the postural tachycardia
syndrome” (2022), the investigators document a number of associations. They report
that patients with postural tachycardia syndrome, or POTS, scored higher on anxiety
and “somatic vigilance”--that is, paying attention to bodily sensations--than controls.
They report that POTS patients, compared to controls, had a “more pronounced
anticipatory tachycardia” when alerted to a coming tilt-table test that would position
them upright. They report that, compared to controls, POTS patients positioned
upright during the tilt-table test had faster heart rate, higher plasma catecholamine
levels, lower end-tidal CO2, and reduced middle cerebral artery blood flow velocity.
The investigators explain the findings by positing that POTS patients have a “classic
Pavlovian fear conditioning” response developed after a prior episode of having
unpleasant symptoms upon standing. They describe the anticipatory tachycardia as “a
physiologic indicator of fear conditioning to orthostasis”—an assertion presumably
designed to bolster the argument that negative past experiences trigger current POTS
symptoms. At the end of the limitations section, the investigators acknowledge, as if
in passing, that they “do not know” if their findings “are a cause or a consequence of
the syndrome.” Despite this significant and obvious knowledge gap, they nonetheless
maintain that the results provide robust support for their characterization of POTS as a
“functional psychogenic disorder.”
Notwithstanding the “more pronounced anticipatory tachycardia” found in the
intervention than in the control group, a key challenge for the investigators’
hypothesis is the significant overlap between the two ranges of heart rates, as
indicated in Figure 1B. As is also clear from Figure 1B, a subset of the POTS patients,
like a subset of the healthy controls, experienced a decline rather than an increase in
heart rate in anticipation of the tilt-table test. These salient details undermine the claim
of psychogenic pathogenesis but are not addressed in the text of the paper.
Beyond that, the investigators conflate association and causation. In fact, the findings
reported here can easily be explained by assuming causality runs in the other
direction. As is common with chronic illness, many people with POTS are more likely
than healthy controls to have anxiety and to measure higher on questionnaires
assessing awareness of physical sensations. They would also be alert to factors or
conditions that could aggravate their symptoms, including a tilt table test. Many
people with POTS would therefore understandably experience a stress response upon
knowing they were about to undergo the unwelcome process of being tilted upright.
And it is not surprising that POTS patients, when in an upright position, have worse
outcomes than controls in multiple domains
The investigators are aware of the shortcomings of their data, but they nevertheless
choose to interpret the research as if it favors their hypothesis—even though it does
not. Their conclusion—that POTS 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”—is unwarranted, appears to stem from the
authors’ confirmation bias, and cannot be justified based on the results presented here.
References
Norcliffe-Kaufmann L, Palma JA, Martinez J, Camargo C, Kaufmann H. Fear
conditioning as a pathogenic mechanism in the postural tachycardia syndrome. Brain
2022; online ahead of print
David Tuller
School of Public Health, University of California, Berkeley; Berkeley, CA, USA
Svetlana Blitshteyn
Dysautonomia Clinic, Department of Neurology, University of Buffalo Jacobs School
of Medical Sciences; Buffalo, New York, USA
David Davies-Payne
Department of Radiology, Starship Children’s Hospital; Auckland, New Zealand
Brendan Delaney
Department of Medical Informatics and Decision Making, Imperial College London;
London, England, UK
Jonathan Edwards
Department of Medicine, University College London; London, England, UK
Mady Hornig, Department of Epidemiology,
Columbia University Mailman School of
Public Health; New York, NY, USA
Brian Hughes
School of Psychology, National University of Ireland, Galway; Galway, Ireland
David Putrino
Department of Rehabilitation Medicine, Icahn School of Medicine, Mt Sinai; New York
John Swartzberg
Division of Infectious Diseases and Vaccinology, University of California, Berkeley;
Berkeley, CA, US
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