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Brain imaging reveals clues about chronic fatigue syndrome

Firestormm

Senior Member
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5,055
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Cornwall England
23 May 2014
Medical Xpress
Brain imaging reveals clues about chronic fatigue syndrome

A brain imaging study shows that patients with chronic fatigue syndrome may have reduced responses, compared with healthy controls, in a region of the brain connected with fatigue. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation.

Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by fMRI (functional magnetic resonance imaging). This reduction of basal ganglia activity was also linked with the severity of fatigue symptoms.

According to the Centers for Disease Control and Prevention, chronic fatigue syndrome is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by exercise or mental stress.

The results are scheduled for publication in the journal PLOS One.


"We chose the basal ganglia because they are primary targets of inflammation in the brain," says lead author Andrew Miller, MD. "Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients."


Miller is William P. Timmie professor of psychiatry and behavioral sciences at Emory University School of Medicine. The study was a collaboration among researchers at Emory University School of Medicine, the CDC's Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia in Italy. The study was funded by the CDC.

The basal ganglia are structures deep within the brain, thought to be responsible for control of movements and responses to rewards as well as cognitive functions. Several neurological disorders involve dysfunction of the basal ganglia, including Parkinson's disease and Huntington's disease, for example.

In previous published studies by Emory researchers, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia. Interferon alpha is a protein naturally produced by the body, as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other groups such as breast cancer survivors.

"A number of previous studies have suggested that responses to viruses may underlie some cases of CFS," Miller says. "Our data supports the idea that the body's immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments."

Treatment implications might include the potential utility of medications to alter the body's immune response by blocking inflammation, or providing drugs that enhance basal ganglia function, he says.

The researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited [not referred] based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents. People with major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not...

Read more: http://medicalxpress.com/news/2014-05-brain-imaging-reveals-clues-chronic.html
 
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13,774
Here's an old Cort article which mentions some of this stuff: http://phoenixrising.me/archives/8707

Doesn't sounds that exciting to me - but maybe there's fun stuff waiting to be revealed. The brains of people who experience a lot of fatigue/pain/laughter/depression/anything are likely to show some differences to health controls.
 

WillowJ

คภภเє ɠรค๓թєl
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4,940
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WA, USA
if I remember right the Georgia cohort is Reeves criteria, so whatever they find probably doesn't apply to any one particular disease. However if they can find biomarkers for fatigue that could potentially help patients with lots of diseases. (They just should use a generic fatigue term as the title.)
 
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15,786
The article is pretty good at least. So odd to see a behavioral psychiatrist speaking about purely neurological issues, plus the treatments listed as examples are physiological, instead of CBT/GET, etc. Looks like progress!
 
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1,446
"The 18 patients were recruited [not referred] based on an initial telephone survey followed by extensive clinical evaluations. The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents."

.
Would that be the Georgia telephone survey which was the foundation for the Reeves Criteria?
.
 

Ren

.
Messages
385
Once again the lack-of-motivation stereotype rears its ugly head. I assume though that some researchers will include statements like this, as they transition from their failed theories to actual science - and as they grab at straws, to justify their years of abuse and negligence.

I do not have a legal background, and I just skimmed this article*, but it would be interesting to know if researchers/psychiatrists/etc. who make such generalizations/allegations could be held accountable for defamation and negligence (at the very least).

"Psychiatrists often believe that they are protected from liability when conducting third-party evaluations..."

"Case law has demonstrated otherwise..."

*http://www.jaapl.org/content/35/2/200.full

When psychiatrists generalize that 17 million individuals - whom they have not examined - lack motivation, is this not a third-party evaluation?

What about when healthcare providers (individuals) author biased secondary-source texts (for the State), knowing that such texts will be used as evidence (in legal settings) to deny individuals with ME/CFS access to entitlements, such as proper medical care and social services support, etc.?

----
edit:
@justinreilly - Any immediate thoughts regarding traction with this for the ME/CFS community? (In your personal, non-legal-advice opinion).

---
edit:
Also of interest: http://www.behaviorismandmentalheal...-psychiatric-diagnoses-defamatory-statements/
 
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Bob

Senior Member
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16,455
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England (south coast)
So this must be the paper?

Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue
Andrew H. Miller, James F. Jones, Daniel F. Drake, Hao Tian, Elizabeth R. Unger, Giuseppe Pagnoni.
May 23, 2014
DOI: 10.1371/journal.pone.0098156
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098156

Free access.

"Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects.
These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks."
 

Countrygirl

Senior Member
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5,429
Location
UK
"We chose the basal ganglia because they are primary targets of inflammation in the brain," says lead author Andrew Miller, MD. "Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients."

This reminds me that when I had a CT scan following a suspected stroke, it revealed lesions through the basal ganglia that had calcified. Has anyone else received a similar result and could this possibly be a result of inflammation? Would this be a common finding in ME?

The scan also revealed lesions through the falx but perhaps that just means I am getting close to falling off my perch and is not associated with ME. :)
 

SDSue

Southeast
Messages
1,066
Emory does not have a good reputation with us, if I recall correctly. However the devil is in the details. We need to see how many devils dance in their publication. Maybe we will be pleasantly surprised. I have my doubts though.

My personal experience at Emory ranks second only to Mayo Clinic in horrific treatment as an ME patient. I was told "we don't believe in that" at the former, and "we don't care about that" and "have a glass of wine" at the latter. Notice the "we" in both instances - it's an attitude that starts at the top and is forced on the providers as they learn to play by the rules.

Unfortunately, those rules are in place at large corporate clinics for two reasons: 1. to maximize profits by minimizing chair time; and 2. to keep statistics of successfully treated patients high.

So while this abstract may sound promising, I believe it will be a LONG time before we see a resultant change in attitudes of caregivers at Emory (or elsewhere) regardless of the details. After all, it is coming from the psychos, who believe that the basal ganglia are mostly responsible for psychiatric problems associated with conditions such as Parkinson's. These include depression, anxiety, affective disturbances, apathy, cognitive impairment, and hedonistic behaviors.

IMHO, anything coming from the psychos won't result in good things for us.

Now, if you'll excuse me, I've got to get back to my "hedonistic behaviors" lol.
 

alex3619

Senior Member
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13,810
Location
Logan, Queensland, Australia
if I remember right the Georgia cohort is Reeves criteria, so whatever they find probably doesn't apply to any one particular disease. However if they can find biomarkers for fatigue that could potentially help patients with lots of diseases. (They just should use a generic fatigue term as the title.)

23. Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, et al. (2005) Chronic fatigue syndrome–a clinically empirical approach to its definition and study. BMC Med 3: 19.

Reference 23 in the paper confirms this. They are vague as to what specific criteria were actually used, but the reference is clear.
 

Firestormm

Senior Member
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5,055
Location
Cornwall England
From the paper: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098156

One mechanism that may contribute to alterations in function and neurotransmission in the basal ganglia in CFS is inflammation [47].

CFS patients have been shown to exhibit a number of immune alterations including the presence of increased inflammatory markers in the peripheral blood and increased production of inflammatory cytokines in ex vivo preparations of peripheral blood mononuclear cells [12][15].

As noted above, a number of inflammatory stimuli including the inflammatory cytokine, interferon alpha and cytokine inducers such as endotoxin and typhoid vaccination have been shown to alter basal ganglia function while also leading to symptoms of fatigue including psychomotor slowing and reduced motivation, both fundamental behavioral processes regulated by basal ganglia structures [19], [20], [47], [48].

Recent work in humans and non-human primates suggests that some of the effects of inflammatory stimuli, in particular interferon alpha, are mediated by effects on basal ganglia dopamine [19], [49]. Indeed, studies in humans using positron emission tomography have shown increased uptake and decreased turnover/release of the dopamine precursor, L-DOPA [19]. Similar results have been found in rhesus monkeys administered interferon alpha [49].

Using in vivo microdialysis from probes implanted in the caudate, dopamine release was found to be decreased after 4 weeks of interferon alpha, consistent with the reduced neural activation in basal ganglia nuclei seen in humans using fMRI in both interferon alpha-treated subjects as well as patients with CFS [19], [49].

Of note, interferon alpha is a cytokine well known to be released during viral infections, and increased levels of central nervous system interferon alpha have been associated with behavioral deficits in animal models of human immunodeficiency virus (HIV) and HIV patients [50], [51].

Thus, the activation of inflammatory pathways by viruses or other pathogens – as well as in a variety of conditions known to be associated with increased inflammation, including obesity and psychosocial stress – may represent one mechanism of altered basal ganglia function leading to symptoms of fatigue in patients with CFS.

Given mechanistic data suggesting that altered dopamine availability may be a consequence of inflammatory effects on the brain, our findings suggest that a good avenue for future studies might be exploring whether drugs that increase dopamine availability in the brain would reduce symptom expression in some CFS patients who exhibit basal ganglia changes and/or increased inflammation.

Acknowledged deficiencies in the cohort:
There are several strengths and weaknesses of this study which should be considered in the interpretation of the data.

First, the sample size of CFS subjects was relatively small. Although there were many more CFS subjects identified by our initial sampling strategy, we adhered to strict inclusion and exclusion criteria to limit the potential influence of factors such as psychotropic medications and psychiatric conditions like depression, both of which can have a profound effect on neuroimaging data.

Moreover, we used validated assessment tools to quantify the degree of pathology in each of the domains relevant to the diagnosis of CFS. This attempt to provide a relatively homogenous sample of CFS patients also runs the risk of producing results that are not generalizable to the “typical” CFS patient.

In addition, these data represent averaged results from each of the samples, and observation of the data indicates there was significant overlap between the groups. Thus, not all persons in our study exhibited reduced neural activation in the basal ganglia, although all CFS subjects exhibited significant fatigue.

Therefore, although alterations in basal ganglia function may characterize a subgroup of CFS patients, such alterations do not typify all CFS subjects and do not account for all instances of fatigue.

In this study non-fatigued controls were used as the comparison group as a starting place in investigating biologic associations with CFS. These non-fatigued controls exhibited some low level of minor medical problems including allergies, muscle aches and pains, gastrointestinal distress, high blood pressure and hypercholesterolemia for which they were taking medications, but not at rates that differed from our CFS sample.

Nevertheless, in order to evaluate whether the findings are specific to CFS, additional studies comparing persons with CFS to persons with more significant illnesses or chronic fatigue would be useful to determine if our findings are typical of CFS patients, or patients with fatigue or illness in general.

Finally, it should be noted that the CFS patients in this study were not drawn from a sample of subjects seeking care at an academic or private practice specialty clinic providing tertiary care. Rather the subjects studied herein were a community-based sample, and despite the rigorous inclusion and exclusion criteria, might more likely reflect findings in the average patient.

Conclusions
CFS subjects free of psychotropic medications and without significant psychiatric disease were found to exhibit reduced activation of basal ganglia structures that correlated with symptoms of fatigue. The findings are consistent with diseases known to affect the basal ganglia and are consistent with basal ganglia changes seen after administration of a variety of stimuli that induce an inflammatory response.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
23 May 2014
Psyche Central

Chronic Fatigue Syndrome Linked to Changes in the Brain

A new brain imaging study shows that patients with chronic fatigue syndrome may have reduced activity in a region of the brain connected with fatigue and motivation.

Using functional magnetic resonance imaging (fMRI), the study found that those diagnosed with chronic fatigue syndrome had less activation of the basal ganglia. The reduced basal ganglia activity was also linked with the severity of fatigue symptoms, according to the study.

“We chose the basal ganglia because they are primary targets of inflammation in the brain,” says lead author Andrew Miller, MD, a professor of psychiatry and behavioral sciences at Emory University School of Medicine.

“Results from a number of previous studies suggest that increased inflammation may be a contributing factor to fatigue in CFS patients, and may even be the cause in some patients.”


The basal ganglia are structures deep within the brain, thought to be responsible for the control of movements and responses to rewards, as well as cognitive functions, according to researchers.

In previous published studies by researchers at Emory University, people taking interferon alpha as a treatment for hepatitis C, which can induce severe fatigue, also show reduced activity in the basal ganglia.

Interferon alpha is a protein naturally produced by the body as part of the inflammatory response to viral infection. Inflammation has also been linked to fatigue in other patients, such as breast cancer survivors.

“A number of previous studies have suggested that responses to viruses may underlie some cases of CFS,” Miller said.

“Our data supports the idea that the body’s immune response to viruses could be associated with fatigue by affecting the brain through inflammation. We are continuing to study how inflammation affects the basal ganglia and what effects that has on other brain regions and brain function. These future studies could help inform new treatments.”


“Potential treatments might include medications to alter the body’s immune response by blocking inflammation, or providing drugs that enhance basal ganglia function,” he said.

For the latest study, researchers compared 18 patients diagnosed with chronic fatigue syndrome with 41 healthy volunteers. The 18 patients were recruited based on an initial telephone survey followed by extensive clinical evaluations.

The clinical evaluations, which came in two phases, were completed by hundreds of Georgia residents. People with major depression or who were taking antidepressants were excluded from the imaging study, although those with anxiety disorders were not, according to the researchers.

For the brain imaging portion of the study, the participants were told they’d win a dollar if they correctly guessed whether a preselected card was red or black. After they made a guess, the color of the card was revealed, and at that point researchers measured blood flow to the basal ganglia.

According to the researchers, the key measurement was the size of the difference in activity between a win or a loss.

Scores on a survey gauging levels of fatigue were tied to the difference in basal ganglia activity between winning and losing. Those with the most fatigue had the smallest changes, especially in the right caudate and the right globus pallidus, both parts of the basal ganglia, the study found.

The study was a collaboration among researchers at Emory University School of Medicine, the Center for Disease Control’s Chronic Viral Diseases Branch, and the University of Modena and Reggio Emilia in Italy. Funded by the CDC, the study was published in the journal PLOS One.
 

Simon

Senior Member
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3,789
Location
Monmouth, UK
Commentary

Summary
Bit of a 'hey ho, not much to write home about' study. The biggest weakness is the use of empiric criteria so these are probably mostly chronic fatigue cases rather than CFS. The biggest strength is that they pursued a specific (and plausible) hypothesis that the problem was in the basal ganglia, and used a gambling test that had already been shown to activate the basal ganglia - so this wasn't a fMRI fishing trip looking for random differences between patients and controls. The correlation between a clinical feature - fatigue - and brain differences during the gambling test also adds weight to the findings.

However, the differences they found were small and patchy, which, combined with the broad empiric criteria makes this study, in my view, of limited interest. Even though these findings are consistent with an inflammatory model of mecfs, which has growing evidence for it.

Background biology
The basal ganglia are a set of structures deep in the brain that have been implicated in fatigue both in neurological diseases and in response to inflammation (eg after administration of the cytokine interferon-alpha as treatment of Hepatitis C patients). The basal ganglia are also a site of reward processing, and this study looked at changes in basal ganglia during a gambling test, a classic test of reward processing.

The basal ganglia has three components, as you can see in this wikimedia pic: the caudate (long, tail-like structure) the putamen and (hidden behind the putamen) the globus pallidus. As for much of the brain, this structure is symmetrical, with left and right caudate, putamen and globus pallidus. This fMRI study looked at each structure separately
473px-Basal_Ganglia_lateral.svg.png


Gambling test
participants had to guess which of two cards presented face-down on a screen was “red” (hearts or diamonds) by pressing one of two buttons on a MRI response box held in their right hand. Two seconds into the trial, the selected card was turned over, and, depending on its color, the participant either won (red card) or lost (black card) one dollar
Unbeknown to the subjects the test was rigged:they started with $16 and all ended with $23 at the end so they had a consistent 'gambling' experience.

Weak definition of CFS
As @alex3619 and @Valentijn have pointed out, this study uses the empiric criteria, which in a poplulation study found a rate of 2.5% for CFS, compared with around 0.3% for a similar earlier study using the Fukuda criteria. The particular issue with the empiric criteria is it uses very 'soft' thresholds: in this sample the average SF36 Physical Function score of 64/100, compared with around 40/100 in outpatient clinic trials. Additionally the sample only had 4.6 CDC symptoms (8.1 total symptoms) suggesting this might be a group of people with general health problems inc fatigue rather than even Fukuda CFS.

Oh, to add to the fun, 39% had done post-graduate study, showing this sample to be somewhat unrepresentative.

Patchy results and Statistical issues
I know, stats are so dull, but so important too, especially in fMRI studies that generate shed-loads of data and so are prone to finding false positive.

Looking at the whole of the basal ganglia there was a difference between patients and controls, but it wasn't big (p=0.02). Figure 2 shows data for individual areas within the basal ganglia and as you can see there is substantial overlap between patient and control scores.
fetchObject.action

As the authors point out:
Thus, not all persons in our study exhibited reduced neural activation in the basal ganglia, although all CFS subjects exhibited significant fatigue. Therefore, although alterations in basal ganglia function may characterize a subgroup of CFS patients, such alterations do not typify all CFS subjects and do not account for all instances of fatigue.
Back to the detail, and the study found:
CFS subjects exhibited significantly reduced activation for winning versus losing trials compared to controls in the right caudate (.., p = 0.014) and right globus pallidus ..., p = 0.019
Again, not hugely significant results. They also found differences for these structures using bilateral data (combined left and right): p=0.047 for caudate and p=0.036 for globus pallidus. However, note no differences in the left caudate or globus pallidus, and no differences anywhere in the putamen. So these results are a bit patchy.
[correction: - bilateral data was in fact significant, but I'm trying to establish if appropriate statistical corrections for multiple comparisons were made].

Also, why was the effect seen in the right structures but not the left? The authors did not predict this, and while they speculate as to why it might be, I suspect if they'd found the reverse pattern they could have happily speculated in the opposite direction too.

Looking at correlation between fatigue and fMRI-measured response to reward - the most interesting part of the study - the results were again patchy. The authors only looked where they'd found results above and found correlations found in the right globus palllidus, but not the right caudate - and didn't mention the bilateral pallidus or caudate. However, they have said that the effects they found in the right globus pallidus were large effects.

The correlations that were found, in the right globus pallidus, were that increased fatigue was correlated with decreased response to reward (the direction that would be expected). It was strongest for mental fatigue (as opposed to general or physical), which again makes sense and the correlation of r-squared = 0.49 (p=0.001) is pretty impressive: equivalent to a correlation coefficient r of 0.7 (0-1.0 scale). This one result does look very good and suggests they might be on to something.

Fatigue vs motivation
Another slightly odd aspect of this study is that it sets out to investigate fatigue and the basal ganglia role in fatigue, but focus on motivation (measured by the gambling test), which ain't quite the same thing.

If the authors had used a better sample, these results would have been more interesting, especially as I think other studies have indicated difference between basal ganglia in CFS patients v controls. But fMRI is a field noted for its false positives so I think a lot more work is needed before too much weight can be put on the role of basal ganglia in mcfs.
 
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15,786
So it sounds like a decent fatigue study, but not an ME study at all. And it might (or might not) have found an interesting anomaly that could indicate subgroups, possibly even the ME subgroup. Hence not completely useless, despite the horrible CFS definition.

No conclusions to really be reached from it, but potential direction for future investigation.
 

alex3619

Senior Member
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Location
Logan, Queensland, Australia
@Simon , is it anywhere clearly cited as to what SF-36 PF scores are typically seen in clinics or outpatient studies? Has anyone reviewed the CFS and ME studies to determine what is commonly found (while acknowledging that most of these studies are primarily on mild patients). This would help us put studies like PACE into perspective.
 

user9876

Senior Member
Messages
4,556
I was wondering how this study would relate to ideas of the lack of blood flowing to the brain. From my very limited understanding the fMRI scan is detecting changes in the flow of oxygenated blood. I think the oxygenated blood affects the magnetic field more than once the oxygen has been released. Then they make an assumption that areas of the brain where processing is happening require oxygen and hence they look for the change between oxygenated and non-oxygenated blood.

So my assumption (although I've not yet read the paper) is that what they are detecting is less blood flow and less oxygen being metabolized in areas of the brain where people have fatigue. It made me wonder if this may relate to work that Julia Newton is doing at Newcastle finding increased acidosis in muscles which I believe is due to the lack of oxygen available to turn something (glucose?) into energy.
 

N.A.Wright

Guest
Messages
106
Commentary

Summary
Bit of a 'hey ho, not much to write home about' study. The biggest weakness is the use of empiric criteria so these are probably mostly chronic fatigue cases rather than CFS.
The study used the Reeves 2005 population but remember that included assessment as:

The clinical visit included detailed medical history, physical examination, laboratory tests, psychiatric screen, and questionnaires to measure functional status, impairment and symptoms, and was completed by 783 persons. Participants were classified as: i) CFS cases, according to the 1994 case definition[22], [23]; ii) non-fatigued controls; iii) insufficient symptoms or fatigue for CFS; or iv) exclusionary medical or psychiatric condition.
and
The follow-up clinic evaluated 751 participants and classified them in the manner described above. Following clinical and laboratory assessments, 71 persons met criteria for CFS, and 212 were determined to be controls.

Further the current study had an extensive exclusion process which included:

Subjects with a score >60 on the 20-item, self report Zung Self Rating Depression Scale (Zung SDS)(indicating more than mild depressive symptoms) were also excluded [25]. All subjects were required to be free of psychotropic medications including antidepressant, antipsychotic, mood stabilizer or anti-anxiety medications for at least 4 weeks prior to brain imaging procedures. No subjects were taken off psychotropic medications for the purposes of the study.

One of the criticism of Reeves work is that it didn’t distinguish between ME and depression, but it would appear that this study went to some lengths to avoid conflation. So as I read it, the study CFS cohort was Fukada, but with identifiable depression or other psychiatric confounders allowed by Fukada removed – so not a bad proxy for a wider ME/CFS population. That said I’d agree that the results are not overwhelming – another study that shows there’s ‘stuff going on’ but that the ‘stuff’ is all over the place. Some discussion about articulating the problems of definitions in the P2P context here: http://www.occupycfs.com/2014/05/22/p2p-agenda-fatigue/#comments
 

RustyJ

Contaminated Cell Line 'RustyJ'
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Another slightly odd aspect of this study is that it sets out to investigate fatigue and the basal ganglia role in fatigue, but focus on motivation (measured by the gambling test), which ain't quite the same thing.

Not so odd. I am pretty sure they were pinning their hopes on finding supporting evidence for a behavioral cause for ME. They failed and I think they tried to spin the study results a slightly more positive way.

The real story here is that the suggestion of a behavioral cause of ME was not supported by the findings.

This study reminds me of the recent Wyller clonidine study, which attempted to prove a behavioral cause of ME. Ironically that study didn't pan out either, thus sorta supporting a biophysical cause.

Okay, I may be a tad cynical here, mainly because of the players involved and where this study was carried out. I think they set out to prove that inflammation in ME was a behavioral response, ie due to the altered reward mechanism, as they have tried to do previously in linking depression and inflammation.

I know on the surface it looks as though they toughened up the Fukuda selection criteria to focus on physical causes. But it's likely they filtered the patients to rule other possible behavioral mechanisms so they could isolate motivation as a defining cause of inflammation in ME.

The positive to come out of the study is that the fatigue inflammation correlations were strong, adding to support for a biophysical cause.

The other positive was that the inflammation motivation correlations were quite poor. So that's good for us too.

What I find personally confronting, with the Wyller study and this one, is that the researchers actually believed they were onto something (ie ME has a behavioral cause) and appeared genuinely surprised with their results. Both teams went ahead and published their findings, despite their failures, so it's not as if they were trying something dodgy.
 
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