Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with CFS, 2008, de Lange et al

Andy

Andy

Retired committee member
An old study but, as shown in this thread, https://s4me.info/threads/top-10-sc...f-citations-tweet-by-dr-mark-gutheridge.7461/, one of the most cited ME/CFS papers in the past 10 years, so thought it might be useful to have here.

Abstract
Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery.

Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients.

Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.
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Open access at https://academic.oup.com/brain/article/131/8/2172/267610
 
"Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery."

Interesting that they define the PACE style CBT for CFS (although this was before the PACE trial results).

Might be a good quote for the people on the NICE committee, or anyone else wishing to point out that CFS-CBT is not standard CBT and that it includes GET as part of its protocol.
 
"Another limitation of this study is that we did not compare CFS patients treated with CBT with CFS patients that did not undergo CBT treatment. Therefore, we cannot exclude that the cerebral alterations are due to non-specific factors other than the CBT treatment. However, the specific effectivity of CBT, compared to other treatments, has been well-established earlier (Prins et al., 2001; Whiting et al., 2001; Edmonds et al., 2004; Stulemeijer et al., 2005), suggesting that the behavioural effects are likely to be the result of CBT, rather than other unspecific factors."
 
Two letters were published in reply. Both are open access:

Can CBT substantially change grey matter volume in chronic fatigue syndrome?
Inge Bramsen
Brain, Volume 132, Issue 6, 1 June 2009, Pages e110, https://doi.org/10.1093/brain/awn207
Published:
29 August 2008
https://academic.oup.com/brain/article/132/6/e110/322958


Change in grey matter volume cannot be assumed to be due to cognitive behavioural therapy
Tom Kindlon
Brain, Volume 132, Issue 7, 1 July 2009, Pages e119, https://doi.org/10.1093/brain/awn358
https://academic.oup.com/brain/article/132/7/e119/324121?searchresult=1
 
This is a horibble study.

The authors didn’t use a control group so it could be that the changes in grey matter volume (GMV) were due to fluctuations in the disease process or the fact that patients were receiving treatment - that is attention and care from healthcare professionals – not CBT per se.

The changes were really small. The authors report this rather deceitfully by saying that the initial differences in GMV between ME/CFS patients and healthy controls decreased by 12%. The figure of 12% sounds impressive but that’s only because it applies to initial small differences. The initial differences in GMV between patients and controls were about 5,5% and they decreased to around 4,8% - that sounds a lot less impressive.

The actual, absolute increase was 4,7 ml (from 669.4 to 674.1 ml) or 0,7%. In comparison: the white matter volume decreased with 0,34%. Anyone looking at these figures honestly, would doubt that these figures represent a clinically meaningful change. The figure of 0,7% that reflects the absolute increase in GMV, is never mentioned in the paper – you have to calculate it from the figures in the table. So very deceitful reporting.

The authors are also not able to propose a credible mechanism how CBT could lead to an increase in GMV. They speculate about neuronal down-regulation due to environmental impoverishment, which CBT is supposed to change, and refer to studies performed on caged rodents and primates.... Yet the 22 ME/CFS patients receiving CBT did not increase their activity level by a significant degree and there was no significant correlation between increase in activity and the increase in GMV. There are other problems with the paper, but really it seems useless discussing these after so many flaws...

Inge Bramsen wrote how the authors have promoted their findings with false claims
In the Netherlands, a press release of the author’s institution even states ‘CBT brings about structural changes in brains of patients’ (Radboud University, 2008).
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So it's very sad to hear that this is one of the most cited papers on ME/CFS in the last ten years. It really makes me lose trust in the current scientific process... So much prejudice, so little critical thinking.
 
Michiel Tack said:
Inge Bramsen wrote how the authors have promoted their findings with false claims

So it's very sad to hear that this is one of the most cited papers on ME/CFS in the last ten years. It really makes me lose trust in the current scientific process... So much prejudice, so little critical thinking.
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That's what I thought on seeing Gutherdige's chart. This study, and the responses from Kindlon and Bramsen, were some of the first things I read when I started looking more seriously at CFS research. It never occurred to me that this would go on to be one of the most widely cited CFS studies of the decade. Grim.
 
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Only yesterday saw this cited on Twitter -- now can't find it anymore but if I remember rightly it was by some FND eminence. [*]

I think criticism of this paper and of the authors' reply deserves to be included in any (p)rebuttal of cognitive behavorists' claims about what their research allegedly shows with regard to benefits from CBT and neuroplasticity.

In addition I think contains some useful data on a) (challenges with) cognitive testing and b) physical activity in CFS / actimetry

Also, thank you @Tom Kindlon for putting a link to your letter on PubPeer, very helpful.


[*] Now found it -- see post below.
 
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Now found it -- Alan Carson replying to some pushback on his response to the NIH's Walter J. Koroshetz:

Andy said:
In response to the NIH's Walter J. Koroshetz posting on Twitter about the ME/CFS Research Roadmap Working Group, Alan Carson, one of the leading proponents of FND, posts "Bizarrely unbalanced group - the only effective treatments to date are CBT and GET but not a single expert in those areas nor a single CL psychiatrist or mainstream health psychologist - i predict vast promises and exactly zero patient benefit will emerge from this".
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Alan Carson on Twitter: "@Sean_WRLDS @NINDSdirector I think it more complex than that particularly for alterations in regional blood glos but even structural change"

https://t.co/detawj5C58“ / Twitter

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@dave30th
 
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