I've had a look at the paper.
For a 'fatigue' study, run by psychiatrists and sleep specialists, it could be much worse.
If all psychiatry-led fatigue/CFS studies were like this, I think we wouldn't be in
quite such a bad situation as we are.
I think it may be an honest attempt at investigative research into idiopathic fatigue, labelled as CFS.
For this study, they equate CFS to unexplained debilitating chronic daytime fatigue that meets the Fukuda criteria. (Their view is that CFS is a subset of unexplained chronic 'fatigue'. i.e. CFS is idiopathic chronic fatigue that meets the Fukuda criteria.)
So they are looking at chronic fatigue, not ME. (i.e. there's no mention of post-exertional exascerbation or any other symptoms other than fatigue.)
They recuited using Fukuda, and they also excluded psychiatric conditions that they say could explain the fatigue (e.g. major depression, psychotic disorders and bipolar disorders.) It isn't clear how rigorous they've been at excluding other psychiatric conditions (and I'm not sure if they've excluded co-morbid depression.)
A central theme of the study is that they've made a good effort to recruit a
relatively narrow cohort of fatigue patients, by excluding patients with daytime sleepiness, sleep disorders, and potential sleep-related causes of fatigue. When they use the term 'pure' chronic fatigue, they are refering to their considerable efforts to exclude sleep-related causes of fatigue and daytime sleepiness.
They have gone to some lengths to distinguishing between daytime fatigue and daytime sleepiness, and to exclude any potential sleep-related pathology, by excluding patients with sleep disorders, and who experience sleep disruption and lifestyles that may induce daytime sleepiness. They've gone to some lengths, even using a "full-night polysomnographic (PSG) recording" to exclude patients whose sleep patterns may cause fatigue or daytime sleepiness.
They have excluded "interfering primary sleep disorders" and also lifestyles that may cause fatigue, such as excessive caffeine consumption and people working night shifts.
Further exclusions were as follows: "Subjects presenting with any formally known somatic or mental condition that could etiologically explain or significantly interfere with fatigue or sleep (e.g., oncologic conditions, autoimmune affection, infectious disease, metabolic or hormonal disorder, insomnia, major depression, psychotic disorder, bipolar disorder); a body mass index higher than 28; an alcohol consumption higher than 2 units per day; substance abuse or addiction; excessive caffeine consumption (>3 units per day) were therefore excluded from the present study."
The cohorts seem to be tertiary care referals, so perhaps severely affected, but I'm not certain about that.
The hypothesis for the study is as follows:
"We hypothesize (1) that attention or cognitive impairment profiles, psychomotor performances, inflammatory and immune activation will differ from healthy non-fatigued controls and (2) that different clinical dimensions in pure chronic fatigue patients are associated to each other and related to clinical symptom intensity."
"...the main objective of the present study was to improve the description of associated dimensions in chronic pathological fatigue regarding cognitive impairment, attention capacities, psychomotor performances or muscular effort power and to investigate the respective relationships between these dimensions in a clinical model of chronic fatigue, namely CFS."
So they are looking at various objectively measurable dimensions that can potentially be used to assess and diagnose CFS. (e.g. cognitive tests, psychomotor performance assessments, muscular effort and cytokine levels.)
Overall, I found the study pretty boring, although they seem to have carried out quite rigorous sleep pattern monitoring, and also objective cognitive tests, objective psychomotor testing, and objective physical fatigability. So they seem to be making an attempt to objectively assess CFS patients. There were differences in the results (between patients and healthy controls) but the diffferences don't seem particularly startling to me. These results may well be useful, and objective testing surely moves us in the right direction, but I can't see how the results would make a massive difference to us. But perhaps I might have missed the potential significance of some of the results.
Cytokines
However, there are some startling and exciting results for the immune biomarkers (i.e. cytokine) readings.
Look at the IL-8 results in the table that @
Sidereal has
posted in this thread.
These are undeniably stunning results.
The levels of IL-8 in patients is more than 221 times higher than that in healthy controls. (19,056 vs 86.) (And the p value is 0.000 which is very impressive. i.e. it means that these results are not likely to come about by chance.)
And it's not just the average levels that are significant in this study, but it's also that the levels of IL-8 correlated with levels of fatigue. (Although exact results for this aren't given.)
So this is a potential biomarker for this particular CFS cohort, that may indicate not only CFS, but also severity of fatigue in CFS.
It seems like quite a stunning finding.
Psychiatrists put that in your pipe, and smoke it!
The differences in some of the other markers are also startling, and consistent (they say) with previous studies.
In the discussion section, they have this to say in relation to these results, which is surely progress for the field of psychiatry:
"
Although their exact role in etiopathogenesis remains controversial and not fully understood, modifications of intercellular communications due to a potentially hyperactive immune reactivity or response might play a crucial role in the maintenance of daytime fatigue in these patients."
Re IL-1b, they say that their findings are consistent with previous studies: "Likewise in our study, pro-inflammatory IL-1b has previously shown higher levels in CFS."
For IL-6, they say that their study is consistent with other studies that show that IL-6 levels are not significantly different between patients and healthy controls.
For the other cytokines, apart from IL-8, (i.e. IL-10, TNF-α, IFN-γ) they say that results from various studies are inconsistent.
Re IL-8, they have this to say:
"
The chemoattractant IL-8 has previously been mentioned as one of the best potential illness marker in CFS (Broderick et al. 2012) and it has also been shown to be significantly increased in fibromyalgia (Wang et al. 2009), a psychosomatic condition that presents similarities and clinical symptom overlap with CFS. In our sample, IL-8 levels were also significantly increased in CFS patients and solely IL-8 showed a positive correlation to daytime fatigue symptom intensity on the FSS."
At the end of the discussion they do seem a little dismissive about the significance and potential use of the immune markers findings, and they are more keen on using some of the other measures to assess CFS, but nevertheless, for psychiatrists, I don't think we can complain too much.
They say:
"
Until now, there is no consensus of how we could represent or demonstrate a clinical condition’s state that is essentially linked to perception and may fluctuate over a time span. However, our study also showed that a physical assessment of fatigue can be significantly related to global sensations of fatigue and even predict symptom intensity as assessed by structured scales like the FSS in clinical conditions as CFS.
"
With respect to the biological findings in immune activity as displayed by cytokine levels here, it remains however unclear if specific cytokines are consistent markers or mediators of fatigue sensations in general.
"
Despite IL-8 showing a strong correlation to perceived fatigue intensity in our sample, these biological assessments should be expanded to other models of chronic daytime fatigue to increase our understanding of their respective roles in global fatigue sensations. Although showing promising and rather consistent results, the more sophisticated and cost-intensive biological measures, like cytokine expression assessments, might currently still be limited to research purposes.
"
In conclusion, we propose that objective measurements of fatigue should therewith be multidimensional and contain assessments of mental and physical fatigue and rather focus on fatigability (kinetic and dynamic aspects of fatigue) and that future studies should explore the ‘time on task effects’ (Pattyn et al. 2008) to come up with a proposal of structured chronic fatigue assessments which can be routinely available and used in daily clinical practice."
With regards to the sleep aspect of the study, they conlude:
"
Hence, with respect to potential treatment attitudes, we propose that co-morbid or overlapping excessive daytime sleepiness should always be excluded in patients presenting with a main complaint of idiopathic chronic daytime fatigue whether corresponding to CDC criteria of CFS or not."
