Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls (2018), Groven et al

hixxy

Senior Member (Voting Rights)
Nord J Psychiatry. 2018 Jul 31:1-5. doi: 10.1080/08039488.2018.1493747. [Epub ahead of print]

Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls.

Groven N, Fors EA, Iversen VC, White LR, Reitan SK.

Abstract

PURPOSE:
The reports regarding the status of the immune system in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have been inconclusive. We approached this question by comparing a strictly defined group of CFS/ME outpatients to healthy control individuals, and thereafter studied cytokines in subgroups with various psychiatric symptoms.

MATERIALS AND METHODS:
Twenty patients diagnosed with CFS/ME according to the Fukuda criteria and 20 age- and sex-matched healthy controls were enrolled in the study. Plasma was analysed by ELISA for levels of the cytokines TNF-α, IL-4, IL-6 and IL-10. Participants also answered questionnaires regarding health in general, and psychiatric symptoms in detail.

RESULTS:
Increased plasma levels of TNF-α in CFS/ME patients almost reached significance compared to healthy controls (p = .056). When studying the CFS/ME and control groups separately, there was a significant correlation between TNF-α and The Hospital Anxiety and Depression Scale (HADS) depressive symptoms in controls only, not in the CFS/ME group. A correlation between IL-10 and psychoticism was found in both groups, whereas the correlation for somatisation was seen only in the CFS/ME group. When looking at the total population, there was a significant correlation between TNF-α and both the HADS depressive symptoms and the SCL-90-R cluster somatisation. Also, there was a significant association between IL-10 and the SCL-90-R cluster somatisation when analyzing the cohort (patients and controls together).

CONCLUSIONS:
These findings indicate that immune activity in CFS/ME patients deviates from that of healthy controls, which implies potential pathogenic mechanisms and possible therapeutic approaches to CFS/ME. More comprehensive studies should be carried out on defined CFS/ME subgroups.

KEYWORDS:
Immunopsychiatry; chronic fatigue syndrome; cytokines; depression; inflammation; psychiatry

https://www.ncbi.nlm.nih.gov/pubmed/30063870

I wasn't sure whether to put this here or in the BPS forum so mods, please move it if BPS would be more suitable.
 
I looked at one of the questionnaires they used, the SCL-90-R which gives scores in categories such as "somatisation", "anxiety", "obsessive-compulsive" and so on.

If you report symptoms such as headache, weakness, restlessness, dizziness, decreased sexual desire, chest pain, etc this counts towards one of these categories. Apparently their thinking is that these are strictly psychiatric symptoms. At this level of intellect, this group is unlikely to produce anything useful.
 
Last edited:
Abstract
PURPOSE:
The reports regarding the status of the immune system in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have been inconclusive. We approached this question by comparing a strictly defined group of CFS/ME outpatients to healthy control individuals, and thereafter studied cytokines in subgroups with various psychiatric symptoms.

MATERIALS AND METHODS:
Twenty patients diagnosed with CFS/ME according to the Fukuda criteria and 20 age- and sex-matched healthy controls were enrolled in the study. Plasma was analysed by ELISA for levels of the cytokines TNF-α, IL-4, IL-6 and IL-10. Participants also answered questionnaires regarding health in general, and psychiatric symptoms in detail.

RESULTS:
Increased plasma levels of TNF-α in CFS/ME patients almost reached significance compared to healthy controls (p = .056). When studying the CFS/ME and control groups separately, there was a significant correlation between TNF-α and The Hospital Anxiety and Depression Scale (HADS) depressive symptoms in controls only, not in the CFS/ME group. A correlation between IL-10 and psychoticism was found in both groups, whereas the correlation for somatisation was seen only in the CFS/ME group. When looking at the total population, there was a significant correlation between TNF-α and both the HADS depressive symptoms and the SCL-90-R cluster somatisation. Also, there was a significant association between IL-10 and the SCL-90-R cluster somatisation when analyzing the cohort (patients and controls together).

CONCLUSIONS:
These findings indicate that immune activity in CFS/ME patients deviates from that of healthy controls, which implies potential pathogenic mechanisms and possible therapeutic approaches to CFS/ME. More comprehensive studies should be carried out on defined CFS/ME subgroups.

KEYWORDS:
Immunopsychiatry; chronic fatigue syndrome; cytokines; depression; inflammation; psychiatry

- Fukuda criteria
+ It's not a BPS study!
 
Small study, lots of correlations tested, a few reached significance. So is this a case of p-hacking? At least they don't try to contort the conclusion to pretend they have found any useful connection between ME and psychological problems. And they do conclude there is a different immune picture in ME, so it's biological.
 
There are issues with the HADS scale in terms of measuring depression. The questions are not great.

What may be interesting is to look at correlations between the cytokines and particular questions and what that may say about levels of disability. Rather than trying to place bad semantics of sets of question answers,
 
Small study, lots of correlations tested, a few reached significance. So is this a case of p-hacking? At least they don't try to contort the conclusion to pretend they have found any useful connection between ME and psychological problems. And they do conclude there is a different immune picture in ME, so it's biological.

Yes, seeing 'twenty patients' and 'subgroups' together had my head in my hands. Pretty certain this isn't the first study finding TNF-alpha differences though, will need to have a hunt...
 
The number of participants are so small that there was probably insufficient power to detect anything in the first place. And indeed, there's a good chance that even the positive findings might turn out to be spurious.

Notice too that one of the "psychiatric" measures was "somatisation", but the scale they used doesn't really measure somatisation (that's probably not even a thing), but in fact counts the number symptoms you report experiencing. So let me fix that for you:
in PwMEs, higher levels of IL10 are associated with greater numbers of self-reported physical symptoms.
Seems much easier to interpret now.

I also shudder when I see patients from two distinctly different clinical groups - in this case PwMEs and matched controls - pooled together to perform a single correlation analysis. No, no, NO!

I'm figuring they didn't measure IL1beta because its present in such small concentration in plasma that its hard to detect.
 
Last edited:
If you report symptoms such as headache, weakness, restlessness, dizziness, decreased sexual desire, chest pain, etc this counts towards one of these categories. Apparently their thinking is that these are strictly psychiatric symptoms. At this level of intellect, this group is unlikely to produce anything useful.

Aren't they also common side effects of medications too? (especially anti-depressants?)
 
'RESULTS:
Increased plasma levels of TNF-α in CFS/ME patients almost reached significance compared to healthy controls (p = .056). When studying the CFS/ME and control groups separately, there was a significant correlation between TNF-α and The Hospital Anxiety and Depression Scale (HADS) depressive symptoms in controls only, not in the CFS/ME group. A correlation between IL-10 and psychoticism was found in both groups, whereas the correlation for somatisation was seen only in the CFS/ME group. When looking at the total population, there was a significant correlation between TNF-α and both the HADS depressive symptoms and the SCL-90-R cluster somatisation. Also, there was a significant association between IL-10 and the SCL-90-R cluster somatisation when analyzing the cohort (patients and controls together).'

"almost reached significance" is meaningless This may not be a BPS study, but it is something the BPSers do - it leaves the impression something of scientific interest has been found when it hasn't.
 
I am stepping out a little beyond my knowledge base/ability to function here so someone will correct me if I've got even this little bit wrong.

So the BPS devotees come to realise that cytokines are of interest in the ME community as a possible avenue of interest.
Et voila -- a paper that shows the association between cytokines and psychiatric symptoms in ME.

Never mind that the evidence of psychiatric symptoms comes from the laughable Chalder fatigue questionnaire.

I think that this shows an avenue for us that needs following up. We must continue to hammer home to all and sundry that the CFQ does not do what the BPS suggest it does and that it is not fit for purpose. Every medical researcher should be made aware of it's abject failings in this regard.

I do think it would benefit us to demolish the CFQ thoroughly so that it is shown to have no validity at all when used for ME (and possibly elsewhere) so that it would also invalidate findings based on it.

Is there in fact a way to do this?
 
Never mind that the evidence of psychiatric symptoms comes from the laughable Chalder fatigue questionnaire.

I think that this shows an avenue for us that needs following up. We must continue to hammer home to all and sundry that the CFQ does not do what the BPS suggest it does and that it is not fit for purpose. Every medical researcher should be made aware of it's abject failings in this regard.

I do think it would benefit us to demolish the CFQ thoroughly so that it is shown to have no validity at all when used for ME (and possibly elsewhere) so that it would also invalidate findings based on it.

Is there in fact a way to do this?
My feedback on content of CDEs (Fatigue) - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) CDE Public Review
https://www.s4me.info/threads/my-fe...atigue-syndrome-me-cfs-cde-public-review.2017

The Science for ME forum also made a submission.

The Chalder Fatigue Questionnaire was subsequently dropped
 
Last edited:
The Science for ME forum also made a submission.

The Chalder Fatigue's Questionnaire was subsequently dropped

I read your post and followed the links. I am very glad this is being addressed (and appreciate the efforts made)but my cognitive functioning is such that everything about this is so unfamiliar to me that it was beyond me to parse what it all means exactly.

As an example, the CFQ was subsequently dropped from what? I know the answer is obvious but I cannot hold onto information (memory?) when presented inside a bulk of unknown info (I don't know if that makes sense at all).

How does this affect the use of CFQ in the paper that is the subject of this thread?

Again, thank you for all your efforts in pursuing this and other issues.
 
I read your post and followed the links. I am very glad this is being addressed (and appreciate the efforts made)but my cognitive functioning is such that everything about this is so unfamiliar to me that it was beyond me to parse what it all means exactly.

As an example, the CFQ was subsequently dropped from what? I know the answer is obvious but I cannot hold onto information (memory?) when presented inside a bulk of unknown info (I don't know if that makes sense at all).

How does this affect the use of CFQ in the paper that is the subject of this thread?

Again, thank you for all your efforts in pursuing this and other issues.
CDE stands for Common Data Elements. Researchers in the US will be encouraged to use scales that are mentioned under the different categories. This could perhaps influence what researchers in other countries do.
 
Back
Top Bottom