Discussion in 'Latest ME/CFS Research' started by SpecialK82, Apr 24, 2012.
Thanks for the update, Firestormm. Have to say the p values for differences between patients and controls look a little underwhelming given the propensity of fMRI studies to throw up false positives:
But I'm pleased they used the '94 criteria (Fukuda), and the correlation of reduction of activity with fatigue levels is certainly encouraging:
I can't imagine Bill Reeves either leading a study like this or presenting the results in such a fashion.
Maybe those with CFS were just too exhausted and had too much else on their minds to care much about winning a simple card game. It sure wouldnt do anything for me. I would like to see the change in blood flow to the basal ganglia if they were offered the chance to take a nap.
Yeah, what if its just boredom? I too would be totally underwhelmed, even if money were involved.
I don't actually think it has as much to do with the nature of the exercise as perhaps some are thinking (thinking being an appropriate word perhaps given the nature of the experiment).
I mean these are established tests and I also just wanted to say that this was (or sounds like) a small almost unplanned bit of research - spur of the moment inspiration almost.
I don't recall hearing that funding had been set aside for it specifically is what I mean I guess. However, if it leads to a focus on the basal ganglia (in this instance) or on more funding for research into specific neurology, then I'm all in favour of course.
I read it all as a 'sweetner' something that might inspire others (as well as in this case the CDC) to move in this direction in future studies.
I wouldn't be expecting much more to be gained from reading the full paper to be honest. I think the internet media have made much out of this simply because it points (again for others) but maybe for the first time for the CDC - to specific (if what goes on in the basal ganglia can be called specific) biological involvement.
Had there been funding made available or a plan in place to specifically look at basal ganglian involvement I think we would be witnessing a far more thorough bit of research here. I just don't think in this case (or perhaps in any other) we should consider this piddly bit of research in isolation.
Anyway, that aside - I was quite chuffed to see my condition featured in the Neurology pages and I hope it does stimulate more CDC research in this little understood area because it might account for pretty much all the debilitation I experience and yes that will include - as does all neurology to an extent - behavioural/emotional features.
Where would I be without me old mate Wiki?
You know after 14 years and at the end of the day I don't give a Macaque-monkey's what is causing/contributing to my condition or what names they apply to it, I just want it isolated and treated effectively
1. If those correlations with fatigue really are r[SUP]2,[/SUP] rather than r then they are very impressive: the correlation with mental fatigue of r[SUP]2[/SUP]=0.49 equates to a normal correlation coefficient of R=0.70, which is unusually high (min=0.0. max=1.0).
So it does look like they only looked at changes in basal ganglie, not the whole brain - just as adreno suggested
"Anhedonia" is a very major feature of depression - this is completely consistent with there being a lack of response in the "reward systems".
This study worries me - as being support for psychologisers and depression (which is organic) being a "cause".
(and does everybody play cards for money? - I certainly don't, much as though I love playing cards.)
Sounds like this would be easily accommodated by the biopsychosocial model, I suspect they would say that it is a consequence of deconditioning and avoidance behaviour that over time has diminished the patient's reward/response system which is why they are reluctant to challenge themselves to overcome their aberrant illness beliefs, they no longer view getting better as a reward so have no motivation to challenge the condition.
The problem is that there is no way to falsify such claims, because every CFS patient (by definition in order to be diagnosed) has had the illness for such a period of time that it is impossible to say whether these neurological impairments are causal or something that develops over time during the course of the illness.
If you could select a group of patients who have had CFS for only a few weeks and see if the same abnormalities are present then you could rule out deconditioning, however you can't actually find anyone like that because it takes so long to find out you've even got the illness, I feel like this is what lies at the heart of many of our problems, I can't think of many other conditions that you have to have had for 6 months to even know you've got the condition.
Like I said (not very well above) if a simple 'card-game' (which wasn't really a card game at all when you consider what they did) could provoke the basal ganglian responses shown in the abstract and commented upon by Blue above - I personally think that a more complex e.g. card-game like SNAP would produce an even greater response/lack of response/stimulant/whatever observable signs. And SNAP is hardly a complex game either - imagine recording a game of chess! Christ my 'basal ganglia' would be all over the shop!
I wonder if Gulf War vets would find a game of cards equally unrewarding?
Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum.
Note : The striatum is the largest component of the basal ganglia.
Why the authors (Unger et al) focused solely on the reward aspect when many basal ganglia disorders involve motor/movement deficits and PEM is the cardinal symptom of ME/CFS (although not for Fukuda) is a little bizarre.
In another GWS study the researchers did at least have a rationale for looking at the basal ganglia particularly which had little to do with reward :
Brain Abnormalities in Gulf War Syndrome: Evaluation with 1H MR Spectroscopy
Just the *thought* of a game of Bridge gets my basal ganglia all fired up, Firestormm!
Unless, of course, I've got depression at the time.
Authors of study: Elizabeth R. Unger1, Andrew H. Miller2, James F. Jones1, Daniel F. Drake2, Hao Tian1 and Giuseppe Pagnoni3
Reeves and Miller worked on many papers together. Now Klimas is working with Miller.
Miller had done a lot of work on depression in disease. Many diseases have inflammation. Many diseases cause depression. Ergo depression causes inflammation causes disease.
There was an International Psychiatrists Conference in Brighton last year that had Depression and (if I remember correctly) Inflammation together for a lecture. It's nothing new I don't think. And so what? I really couldn't give a flying monkey as I've said before.
I can't see them determining that some itty-bitty bit of the brain is somehow unique to causing neurological conditions that doesn't also impinge on what are categorised as 'psychiatric'. I mean it's all biological at the end of the day.
It would be interesting to see this Unger study repeated with 'ME', Depression, and Normal patients don't get me wrong. Let's see just to what degree this (and other parts) of the brain are working poorly or in overtime mode. Let's see if there are definite differences. But I bet any differences will not be as significant in all areas as some might like.
Then again I could be wrong. I don't mind either way. Wish they'd just change the spark plugs and get on with it. Might help prevent all the misfiring when it comes to research direction
Actually he believes it's the other way around. Can we please get the conspiracy theories behind us?
Miller's hypothesis is that something in the immune system causes inflammation, which in turn causes depression and other diseases. Personally, I'm very glad to have him involved in ME/CFS. If you take a look at his earlier research instead of cherry-picking some studies that don't even demonstrate your theory, you'd notice he is one of the 'good guys'.
For example, he recently demonstrated that Depression and fatigue during chronic IFN-? administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.
He also did a clinical trial to see if a monoclonal antibody (infliximab), which is used in auto-immune diseases, helps to treat treatment resistant major depression. That study is completed and the results are promising. This also further supports his hypothesis about immunological abnormalities in MDD.
But the most important thing is that, in this study, he nowhere suggests that depression or psychological factors are responsible for decreased activation of the basal ganglia. In fact, he suggest infection (amongst other things) may be responsible for this.
Bolded section does not negate what I said. Nowhere above does he say inflammation causes depression. He actually says depression causes immunological changes and further on links immunological changes to disease causation.
Even more clearly he states in this interview that depressed patients produce an increased inflammatory response which possibly leads to disease.
Please leave out the inflammatory remarks about me being a conspiracy monger. I have been around long enough to know that most associated with Reeves do not believe me/cfs is biological. Reeves has gone on record to say as much and has thwarted any attempt to further biological research.
Yes Miller does go on to say the immune response leads to disease, but in our case this is irrelevant.
Since the CDC doesn't think we have a disease, they can say we just have depression with subsequent inflammation/ immune response in some. This is the danger with what they are trying to do.
He's not saying that depression causes immunological changes. He's merely saying that depressed people have an increased inflammatory response:
''increased inflammatory responses to stress in depressed patients may be a link between depression and other diseases.'' Furthermore he suggests that ''too much inflammation, either at rest or during stress, may predispose people to become depressed or stay depressed.
How you can conclude that he's saying that it's the depression causing inflammation and immunological changes is beyond me.
It's also interesting you referenced one of his studies to support your believe that Miller believes depression causes inflammation. But a look at the full-text reveals a completely different picture:
I mean this in the nicest way possible, but if you twist a scientist's hypothesis just beause he has been associated (in only 3 studies) with Reeves I think it's fair to say that's not an objective argument.
Have you read Cort's summary of Miller's talk at the Ottawa IACFS conference? I have linked it in one of my above posts and it's very relevant in our case.
There is no evidence they're doing that. Quite the contrary, actually. Unger could easily conclude that as one of her working hypothesis in the FASEB abstract, but instead she concluded it supports a biologic theory of this disease. Miller himself could easily do the same at the IACFS conference, but he actually suggests the results of this study may be caused by infection.
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