“Sustained Arousal”

Wyller’s “sustained arousal” hypothesis proposes that a persistent stress response is causing many of the symptoms found in Chronic Fatigue Syndrome. In particular,  Wyller believes this persistent stress response is mucking up autonomic nervous system functioning in the disorder.

We have suggested that the autonomic alterations, as well as other features of CFS, might be attributed to a persistent stress response or “sustained arousal”

Wyller believes negative expectations and thoughts are resetting autonomic nervous system functioning  in "CFS"

Wyller believes negative expectations and thoughts are resetting autonomic nervous system functioning in “CFS”

That sentence is a little hard to understand given that the autonomic nervous system is part of the stress response (“a persistent stress response causes a persistent stress response?”). Wyller’s grasp of the “stress response”, however, appears  to equate more to a barrage of stressful thoughts and ideas than to physiological problems.

 “Of note, this model predicts that expectancies modulate autonomic nervous activity… We hypothesized that expectancies might be an important determinant of the autonomic responses in CFS.”

Few would disagree with the idea that “expectancies” or negative expectations would affect ANS activity. The sympathetic nervous system or fight or flight system, after all, is designed to help us deal with stressful situations of which negative expectations are one.

While others are looking for physiological reasons to explain the ANS dysfunctions, Wyller appears to believe that negative thoughts (“expectancies”) are the primary movers of autonomic nervous system dysfunction in ME/CFS.

For Wyller, ME/CFS appears to be a kind of internal PTSD where the mind so over-reacts to symptoms produced in the body that it actually changes the physiology of the body.

He tested that idea in this study.

The Study

Biopsychosoc Med. 2014 Sep 15;8:22. doi: 10.1186/1751-0759-8-22. eCollection 2014.Orthostatic responses in adolescent chronic fatigue syndrome: contributions from expectancies as well as gravity. Wyller VB, Fagermoen E, Sulheim D, Winger A, Skovlund E5, Saul JP.

Wyller measured autonomic variables such as heart rate, blood pressure, stroke volume, and heart rate variability while people with Chronic Fatigue Syndrome were lying down, while they imagined themselves standing up, and while they underwent a 20 degree tilt table test.  According to Wyller his CFS group should demonstrate more ANS dysregulation as their negative expectations increased during the mental imaging period and then during the tilt test.


It didn’t work out that way.

Wyller found significantly altered autonomic nervous system findings in his ‘CFS’ group when they were lying down at baseline in a rested position. That was to be expected. Increased heart rates and decreased heart rate variability found during rest has been documented  in ME/CFS before.

During the imagining standing session SNS function did become altered (subtly altered) in Wyller’s CFS group, but where the rubber meets the road – in the tilt table test – it did not.  According to Wyller’s hypothesis, the negative expectations his ‘CFS’ group harbored regarding the tilt table test should have dysregulated their autonomic nervous systems when they actually got on the tilt table.


Wyllers “CFS” group performed opposite to how his hypothesis suggested they would perform

That didn’t happen. In fact, contrary to Wyller’s hypothesis the more stress his group was put under the better their autonomic nervous systems appeared to perform relative to his controls. Compare the seven measures of ANS functioning that were “off” during the baseline rest period to the four that were “off” during the mental imagining test, to the zero measures that were “off” during the tilt table test.

Not only were more measures of ANS functioning ‘off’ in Wyller’s ‘CFS’ group during the baseline rest period than the stressful mental imaging task, but the degree that they were off – the significance levels –  was much greater as well (avg. significance baseline rest period vs mental imaging – p<.015  vs p< .038).

In fact, in this study the more stress that was present the more the CFS patients looked like healthy controls – just the opposite of what Wyller’s hypothesis predicts.

That didn’t keep Wyller from arguing that ‘expectancies’ or negative expectations were still driving the ANS dysregulation seen in his ‘CFS group’ during the baseline period (presumably because they were worried about taking a tilt table test.)

“Taken together, these results are congruent with different expectancies among CFS patients.”

That  assertion belies the fact that studies have demonstrated ANS alterations both at rest and during sleep in studies in which tilt table tests were not imminent.

Wyller’s last study found that, contrary to his hypothesis of sustained arousal, Clonidine – a sympathetic nervous system suppressor – made his patients worse, not better. In this study his hypothesis struck out again.

Subtle Findings Need Not Apply

“In both groups, the changes from baseline are rather subtle.”

Wyller noted that his findings were rather subtle and then proposed more studies examining how negative expectations were driving physiology in ME/CFS. Whatever Chronic Fatigue Syndrome is, however, it is not a “subtle” disorder. Dr. Bateman recently noted that ME/CFS is the main cause of illness-related school absence in the U.S.  She also noted how difficult it is to get adolescents to miss considerable amounts of school time. ME/CFS is a profoundly disabling disorder that produces, in some cases, fatigue so extreme as to almost defy belief.  Subtle findings are not an answer.

Backlash Imminent

Wyller’s overt emphasis on the mind in ME/CFS runs the risk of what Wessely’s similar emphasis did: producing a backlash that throws the baby out with the bath water.

It’s surely true that anticipation and the accompanying sympathetic nervous system activation it causes cannot be helpful in ME/CFS. Try imaging a situation in a stressful light, and then put it in a less stressful context and observe how your body reacts.  Reducing negative anticipation and  other forms of mental and emotional stress in a disorder in which both axes of stress response (ANS, HPA axis) are active is a good idea – there’s just no indication that it’s the answer for the vast majority of ME/CFS patients.

With that in mind, I propose a new guideline for assessing the effectiveness of potential research studies called the Toni Bernhard Rule.

The Toni Bernhard Rule


Toni Bernhard has written a book on using mind/body techniques to improve wellness in ME/CFS and other disorders. Her health remains severely impaired.

Toni Bernhard is a former law school professor and experienced meditator with a severe form of ME/CFS. She has written several books and many blogs on ways to improve one’s well-being using mind/body techniques. Despite years of this practice, however, she remains physically quite disabled. If anyone understands the effects of the mind on the body, it’s Toni Bernhard.

The Toni Bernhard rule suggests that if a proposed study could help explain why Toni is ill it should be given top priority. If it can’t, funders might want to think again. This is not to say that stress reduction is not valuable – it is, but if you’re committed to getting at the core of this illness, asking yourself whether a proposed study might help explain Toni Bernhard’s illness might be a good start.

Is Wyller Studying Chronic Fatigue Syndrome?

The normalization of autonomic nervous system that occurred in the CFS group during tilt table testing in this study runs contrary to Wyller’s past studies, and that brings up another question – just who is Wyller studying?

Wyller has chosen throughout his work to use his own definition of chronic fatigue syndrome.  The Wyller definition of ME/CFS (“three months of unexplained, disabling, chronic/relapsing fatigue of new onset”) requires no symptoms beyond fatigue.  This study, which found that thirty-one percent of his ‘chronic fatigue syndrome’ group couldn’t even meet the mild Fukuda criteria for CFS, suggests that he’s often not studying Chronic Fatigue Syndrome as it’s been defined and researched.

Most researchers use Fukuda as a matter of course. For years, the largest medical research funder in the world, the National Institutes of Health (NIH) in the U.S., required ME/CFS researchers to use Fukuda to ensure at least some degree of homogeneity prevailed in research studies.  (Now, recognizing the need to assess the effectiveness of other definitions, it’s become open to other definitions being used. In contrast to Wyller’s definition, however, these definitions were developed by consensus groups.)

Wyller is not studying  the same type of  'CFS' patient that the vast majority of   ME/CFS researchers are.

Wyller is not studying the same type of ‘CFS’ patient that the vast majority of ME/CFS researchers are.

By not using the standard research definition of ME/CFS Wyller’s put a question mark on the significance of every study he’s published. Given that almost a third of the participants in his latest study couldn’t meet the Fukuda definition, it’s a pretty big question mark that makes it impossible to compare his findings to others in the field. Why Wyller is willing to sacrifice a degree of validation or even pertinence in the ME/CFS research field in order to have his way in this area is unclear.

Given the consensus in the field that’s formed around an even more stringent definition of ME/CFS – the Canadian Consensus Definition – the participants in his studies are probably a poor match for what most in the field consider to constitute Chronic Fatigue Syndrome.


Wyller’s  “sustained arousal” model of ME/CFS appears to be largely built on the idea that false perceptions  and negative expectations alter autonomic nervous functioning which in turn causes many symptoms. In this study he hypothesized that the perception that standing is going to be harmful would raise sympathetic nervous system activity in his ‘CFS group’ during tilt table testing.  Contrary to his ‘sustained arousal’ hypothesis, however, autonomic nervous system functioning was at its worst in his CFS group during the baseline rest period and improved as stress and negative expectancies increased.

The large of number of study participants who did not meet the Fukuda criteria suggest Wyller is not studying the same kind of “CFS” patients as the  rest of the ME/CFS research field, making it impossible to know how (or even if) his findings relate to the rest of the field.


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