A commentary from a group of researchers, including Todd Davenport, Carmen Scheibenbogen, Karl Tronstad, Jonas Berquist, David Tuller, Uta Behrends, Mark Vink, and Luis Nacul, has challenged conclusions drawn in an NIH paper – which ME Research UK has written up in detail – published in February 2024, written by Brian Walitt and colleagues.
Walitt et al., concluded that post-infectious ME/CFS is a ‘disorder’ defined by altered effort preference, leading to activity avoidance and subsequent deconditioning (the process of losing physical strength through being ill or inactive).
In relation to Walitt’s conclusion, the authors of the commentary state:
“We believe this interpretation risks reinforcing scepticism about the serious biological nature of ME/CFS and its hallmark of post-exertional malaise (PEM), as well as its potential misclassification as a mental health condition”.
Specific concerns raised by Davenport et al., include:
- Walitt and colleagues used a single, rather than 2 day, cardiopulmonary exercise test (CPET), which may not fully capture the impact of PEM on recovery and exercise capacity. In fact, the authors of the commentary remind readers that the IOM caution that “a single CPET may be insufficient to document the abnormal response of ME/CFS patients to exercise”. According to Davenport and colleagues, “using a single CPET introduces a threat to validity in Walitt’s study”.
- The control group was not adequately matched using deconditioned participants – something Davenport and colleagues say is essential to differentiate between deconditioning and ME/CFS.
- Walitt and colleagues characterised PEM as “discomfort associated with exertion”, and went on to describe how participants may limit activity to avoid this discomfort – this downplays the severity of PEM and “provides additional justification for clinicians, researchers, and policymakers to discount its severe and life-altering effects”.
- One of the measures used in Walitt’s study, which required all participants to be equally able to complete a test without becoming fatigued, had not been validated in people with ME/CFS. The increasing effect of PEM during the test on participants with ME/CFS, due to the test itself, may limit the results.
- Very small sample size: only 8 people with ME/CFS and 9 healthy controls
In the conclusion of the commentary, the authors state:
“We are concerned that the analysis in this study are under-powered and lack ecological validity….. we urge the interpretation and dissemination of these findings with utmost caution, ensuring that they accurately reflect the complex and debilitating nature of ME/CFS.”
The commentary, published in nature communications, was received by the journal soon after Walitt’s paper was published in February 2024, but regrettably was only recently published in October 2025.
Notably, concerns relating to effort preference were also raised by ME Research UK in a write up of Walitt’s study, and when ME Research UK questioned Walitt at the 2024 Invest in ME Conference, he stated that “decision-making” only plays a small role in ME/CFS mechanisms, and directed attendees to a 5.5-hour seminar for more details.
