Any Light gene expression study is big news. If you’re not up on the Lights’, two of their past studies showed astonishing changes in gene expression after exercise in chronic fatigue syndrome. They have a third bigger study in the works plus a Lyrica ME/CFS gene expression study (and probably a few others..)
In this study the Light’s examined gene expression levels in chronic fatigue syndrome and post-prostate cancer fatigue. ME/CFS patients needed an exercise challenge to light up the charts in their past two studies but no exercise challenge was used in this study. That suggested this study might not find much and, indeed, fewer genes popped up than before, but that mean they didn’t find much; on the contrary..
Fatigue in Cancer and Chronic Fatigue Syndrome (ME/CFS)
Many disorders can cause fatigue but the physiological causes of fatigue are not clear. Fatigue is worse in ME/CFS than post-cancer fatigue, and the gender balance is decidedly different (mostly women in ME/CFS), but cancer researchers point to many of the same suspects as do ME/CFS researchers; pro-inflammatory cytokines, anemia, HPA axis, serotonin neurotransmitter issues, muscle and ATP metabolism.
This suggests it’s possible that different triggering factors (cancer/ cancer treatment; infection in many people with ME/CFS) spark similar responses at the molecular level. If that’s true then finding drugs to reduce fatigue just got a whole lot easier.
These two disorders are quite different, however. While many symptoms are similar (fatigue, reduced exercise ability, poor sleep, muscle weakness, cognitive problems) some significant differences exist, including the all-important post-exertional malaise, widespread muscle and joint pain and orthostatic intolerance found in chronic fatigue syndrome.
In this study the Lights and Dr. Bateman measured the expression of 46 genes from adrenergic (sympathetic nervous system), immune, metabolite detecting, mitochondrial/energy and transcription factor pathways in 30 fatigued prostrate cancer patients, 39 ME/CFS patients and 22 healthy controls. Many of these genes were the same ones the Lights used in prior ME/CFS studies.
While the post-prostrate cancer fatigue (PCF) patients were more fatigued than the healthy controls, the ME/CFS patients were significantly more fatigued than the post-cancer patients. A similar percentage of ME/CFS (51%) and PCF patients (43%) had evidence of mild to moderate depression and similar percentages of people with ME/CFS and PCF reported sleep problems (90/92%).
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The remarkably different patterns in gene expression found suggested fatigue was being produced in very different ways in these two disorders. In fact, of all the genes that were expressed differently in either PCF or ME/CFS from the healthy controls, not one was expressed differently in the same direction in the two disorders. In order words if a gene was over-expressed in PCF, it was under-expressed in ME/CFS.
Eight of of the 46 genes in PCF patients differed from both the ME/CFS patients and the healthy controls. Only two genes in the chronic fatigue syndrome patients differed from both the PCF patients and the healthy controls. The low number of differentially expressed genes in the ME/CFS patients highlighted the need for an exercise challenge in this disorder
Mitochondrial and Inflammation Genes Pop
A gene that had been implicated in a past ME/CFS study by another investigator popped up. The decreased expression of HSPA2 in two studies by independent groups suggested something, indeed, is awry in the mitochondrial pathways of people with ME/CFS. The Light’s suggested the down regulation of this gene could be reflect a problem in producing energy or be the result of fatigue and subsequent inactivity.
After not showing abnormal expression of any of the genes that were highlighted in past exercise studies, ME/CFS patients showed abnormally high expression of a gene the Lights had never tested before (P2RX7). This gene, which regulates pain levels, particularly in inflammation associated pain, was significantly down-regulated in PCF.
Genes That Make Your Symptom Worse
Next, the Lights determined which genes appeared to contribute most to fatigue and pain. These were genes that were most highly active in the worst off patients (and less expressed in those with lesser degrees of pain and fatigue).
None of the genes mentioned above appeared to make a difference in the amount of fatigue and pain either group experienced; instead genes with normal expression at the group level were implicated. (The expression of these genes varied markedly within the ME/CFS group but they did not appear to be elevated or reduced compared to the other groups.)
We’ve seen this pattern – genes or cytokines at normal levels that appear to be having abnormal effects – in Dr. Broderick’s work with Dr. Klimas. Their gene expression networks suggest a genes place in a network is more important than its level of expression (relative to other disorders). It appears that some genes take on extraordinary importance in dysregulated networks. They don’t need to be unusually active to affect the body; they simply need to be present. These genes or cytokines that are missed in most studies.
A Common Fatigue Producing Pathway Shows Up…
Thus far the two groups have looked very different, but when symptoms were taken into account; i.e when they determined which genes were most highly associated with fatigue and pain, similarities emerged.
Fatigue severity in ME/CFS was best predicted by lower expression of a gene called DBI and higher expression of a gene called TNF. The fact that fatigue severity in PCF was associated with lower expression of DBI and higher levels p P2RY1, suggests DBI may be a key player in producing fatigue, in general.
The diazepam binding inhibitor (DBI) – better known as the ‘GABA receptor module’ – has the ability to regulate energy production, modulate mood, and affect adrenal steroid production (testosterone, corticosterone). A GABA/glutamate imbalance has been proposed in ME/CFS/FM. (By reducing glutamate levels, Lyrica may be restoring the GABA/Glutatmate balance in the central nervous system in fibromyalgia.)
- Dig Deeper: Glutamate – One More Piece in the Chronic Fatigue Syndrome (ME/CFS) Puzzle? The Neuroinflammatory Series
The fact that DBI popped up in a 2008 ME/CFS study examining 1,467 stress-response genes is gravy. That study put DBI into the ‘regulators of energy metabolism’ category (and called it acyl-coenzyme A (acyl-CoA) binding protein.)
TNF – an unpregulated gene, tumor necrosis factor has been associated with fatigue severity in some ME/CFS studies and not in others. A key pro-inflammatory cytokine, TNF is associated with the kind of immune response (innate) most often associated with ME/CFS.
Oxygen Delivery and Blood Vessel Problems
Another gene that fits smack dab in the middle of some major ME/CFS hypotheses – VIPR2 – was under-expressed in ME/CFS patients. The fact that it was down-regulated in the post-prostrate-cancer fatigue patients, as well, suggested it might be able to spark a fatigue response in other disorders.
This gene’s regulation of hypoxia (low oxygen levels) and vasodilation (blood vessel size) in, get this, the central nervous system (and the periphery) is intriguing given the low cerebral blood flows, the low VO2 max and workload in the repeat exercise studies, the findings suggesting oxygen is not being used by the mitochondria and the high rates of migraine found in ME/CFS.
Interestingly, this gene also popped up in another ME/CFS study but it was over-expressed (instead of being under-expressed).
Exercise Needed to Highlight Abnormal Gene Expression in Chronic Fatigue Syndrome (ME/CFS)
This reinforces our prior interpretation that dysregulated fatigue pathways in CFS are more clearly revealed after exercise than at rest. The Study Authors
This study highlighted how important it is to challenge people with ME/CFS with exercise. Many of the 46 genes in this study were abnormally expressed in prior ME/CFS studies that incorporated exercise challenges but only two were highlighted in this study.
The fact that many more genes were abnormally expressed in PCF – a much less severe condition – may indirectly validate the key role post-exertional malaise plays in ME/CFS. People with ME/CFS have been speaking about the hit exertion brings them from the day this illness burst on the scene. The term post-exertional malaise was coined by the ME/CFS community. “Crash’ and ‘relapse’ are used frequently.
Post-cancer patients coined their own term for the brain-fog they experience (chemo-fog) but they haven’t coined a term for PEM.
Fatigue to ME/CFS may be somewhat akin to snow for Eskimo’s; a term with many different permutations. One study highlighted 5 different types of fatigue present in ME/CFS that are not present in the population at large.
We don’t know what results a PCF gene expression study with an exercise challenge would bring, but it’s clear that substantial gene expression differences exist when PCF patients are at rest, and, at least for these genes, that’s not true for ME/CFS.
Maximizing Research Opportunities
Research funds are hard to come by, but the Lights’ in Utah, Dr. Klimas in Miami and Dr. Baraniuk in Georgetown are getting ME/CFS research done by using ME/CFS patients as control groups in studies funded for other disorders. This study, for instance, was funded by the Huntsman Cancer Institute and the NIH.
It’s hard to know what the treatment implications of these findings are. Finding a common molecular pathway for fatigue would be a huge, huge finding that would undoubtedly interest drug companies.Hopefully fatigue researchers will start probing for DB1 in other disorders.
The study also provides other potential targets for fatigue and pain relief in ME/CFS. Gene expression findings, however, need to be validated by studies which indicate that the protein the gene codes is actually increased in the body. These findings also need to be validated in other studies.
Changes in group gene expression results suggested the fatigue in post-prostrate cancer and ME/CFS patients is being produced in very different ways, but taking symptom severity into account revealed a potential common pathway involving energy metabolism, GABA/glutamate and the HPA axis. Finding a common fatigue pathway would be a huge boon for drug companies seeking to develop drugs to relieve fatigue.
Two genes involved in mitochondrial energy production and inflammation that were highlighted in the ME/CFS group could at some point provide targets for interventions.
The few genes highlighted in the ME/CFS group contrasted in the large numbers of dysregulated genes in the Lights past exercise studies suggested exercise challenges are needed to fully explore gene expression differences in chronic fatigue syndrome. The fact that this is so in ME/CFS but may not be happening in PCF – a much less severe condition – suggests post-exertional malaise may indeed be a unique feature of chronic fatigue syndrome.
Looking more like my thoughts are proving out. This is what I think: First we are genetically pre-disposed and something may trigger a genetic mutation, which may cause autoimmune dysfunction and along with it inflammation.
I just watched one of the best videos I’ve seen in awhile on nutrition and the potential help that a change in diet could bring. It’s long —-but, well worth watching. What if our answers are what is on the other end of our forks????? We will try whatever pill is recommended to us —but, what if . . . .a change in diet could be the one thing that would make a difference. (I KNOW it is for me.)
Thank you so much for this information Cort. Having another bad brain day in bed, but think this is pretty great news to receive on my 27th ‘Anniversary’ with ME. 🙁 I think we all know it takes the ‘potential of a huge market’ to get Big Pharma’s attention to get the funding we need. I have such hope this is it.
I hope so…If it is it will take some time but its encouraging that researchers are looking at fatigue in this different disorders. If they could find a common pathway buried way down deep underneath this different triggering factors, that would huge.
Great article. Substantive. Encouraging.
Very interesting, Cort
I think you are right that the main conclusion is that these genes aren’t much affected for CFS without the exercise challenge, and that the pattern of ‘fatigue’ genes is different from that in Androgen-treated cancer patients.
But with 46 genes and 3 groups there were a huge number of comparison and the usual problem in gene expression is false positives – do you know if they corrected for multiple comparisons?
Also, these seems a similar model to that being used by Carmine Pariente in the UK, looking at Hep C patients after Interferon therapy who similarly suffer from fatigue – though I don’t think he is looking at gene expression.
Interesting idea to learn about CFS by using them as controls in other experiments…
Firstly congrats to Cort – that was quick off the mark. I’m still plodding through this one.
Re your queries Simon its worth trying to get hold of the full paper if possible. Kathleen Light has previously written extensively on the methodological issues in gene expression studies – e.g. in this paper :
so is very much aware of the pitfalls and this study is very much ‘eyes open’.
They’ve actually very cleverly gone out of their way to eliminate as far as possible the possibilities of false negatives (cluster analysis; conservative levels of significance, use of Ancova for example) and for confounding factors (the obvious gender bias in prostate cancer etc).
I actually find the limited findings for ME/CFS quite comforting. Many of the previous genes dysregulated following exercise challenge were andrenergic/sensory related yet we definitely don’t feel OK in a resting state so something else must be going on. The fact that (despite the differences) fatigue severity was most closely correlated with DBI in both patient groups suggests to me that there’s a significant issue there.
Another useful point take from this paper is the difficulty in interpreting gene expression that is either up or down regulated. I’ve proposed that ME/CFS is a neurological problem caused by an imbalance between glutamate and GABA with GABA relatively downregulated. These findings would suggest the opposite (DBI appears to reduce the efficiency of GABA a receptors so a lower level of DBI should help with GABA transmission. Yet the authors point out that an elevated expression of a gene (e.g. that coding for TNF-a) doesn’t necessarily result in higher levels of TNF-a. They point out that gene expression may be the result of homeostatic mechanisms to correct an existing imbalance. So going back to DBI, reduced DBI expression may be a feedback loop attempting to correct low levels of circulating GABA.
That’s not to say of course that these serum results will be reflected in the central nervous system so they really say nothing with respect to my own little theory. Interesting though!
Generally I’m really impressed with the approach they’ve taken ‘piggy backing’ ME/CFS to other conditions were fatigue is an issue.
I doing so (as Cort noted) they’re able to leverage funding from a much larger pot than normally available to ME/CFS;
ME/CFS as a disabling condition is reaching a much wider audience of clinicians and researchers who would normally run a mile from it;
plus its difficult to suggest that we’re comparing (organic) apples with (psychosomatic) pears when exactly the same mechanism appears to play a key role in fatigue severity in both cases. Not that a minority won’t attempt to suggest that cancer related fatigue isn’t just a maladaptive response to a life threatening illness.
PS – as a side note – the anti-androgen therapy given to these prostate cancer patients resulted in their testosterone levels being zero which you might expect to have a marked impact on energy. Yet as a further confounding factor a large proportion were also receiving either chemo or radiotherapy – both of which are known to result in cancer related fatigue.
Thanks for all the background Marco – in particular explaining this
“So going back to DBI, reduced DBI expression may be a feedback loop attempting to correct low levels of circulating GABA.”
So many twists and turns in the body. 🙂
DBI relates more to the CNS than immune system.
DBI is affected by androgens such as testosterone. Maybe this might explain why many more females seem to be struck down with CFS.
Maybe I need to order some testosterone.
Not much immune stuff showing up in this result.
I’ll keep maintaining that immune factors may be a trigger in this blasted disease, but the ongoing tissues relate to the CNS / neuroinflammation. More focus in this area please.
I’ve often questioned if there is an imbalance between the levels of hormones. Since many of us females with POTS and MCAS also have endometriosis —which has been thought to be related to MCAS and estrogen dominance. Could there also be an imbalance with the levels of estrogen vs. either testerone or progesterone. I question this in men also. As far as I know, docs don’t check men’s estrogen levels. There again if there is an imbalance, that could be addressed with diet. So many ways to imbalance hormones with the xenoestrogens in our environment and bad habits that we do (soy, flax, microwaving in plastics, etc.).
You’d be surprised (or maybe not) how many of us male ME/CFS’ers have sex steroid issues.
My testosterone tanked from the high 20’s (normal all age range approx 9-38 nmol/L) to 7 (aged mid 30’s) in the space of around ten years. Raised estradiol also. Normally you expect a 25% drop in peak T levels by the time you’re in your seventies.
This was considered “normal” by a professor of endocrinology who didn’t even bother testing free T.
Now there’s an admission! Not surprised I have ‘hot flushes’.
Marco, That’s what I’m finding with the guys I talk to. They for sure won’t say if there is a problem there. But, they are always looking for answers.
Watch the above video, I posted. It is showing that two of the worst foods for prostate cancer is chicken and eggs. I know that with even organic chicken they are feed soy and are high in estrogen. My doc told me to stop eating any fowl as he feels it imbalances the hormone levels terribly. After my complete hysterectomy, I couldn’t get my hormones to balance out and this was the one thing he told me to do and it really helped with the hot flashes. Another thing is increase your cruciferous veggies. That helps to balance estrogens. (You can also take DIM – which also helps with this.) That same doc also said that he thinks eating chicken really messes up little boys and their hormone balance and growth. But, he felt that it was just bad all the way around for us. The video above for sure gives us a lot to think about. DIET CHANGE!!!!!!
I didn’t know that DBI. Some alternative health docs do use testosterone. Jeez, you gotta think the female predominance probably relates to hormones but then again I’ve heard females have a much more complicated immune system. Then again the two are pretty tightly integrated.
I agree on the neuroinflammation and for me I think the blood vessel, hypoxia issue is crucial. I liked seeing that one gene pop up.
Is there a link for the study mentioned that differentiated five types of fatigue for ME/CFS? I have had such a difficult time explaining to people that “tired” for me just isn’t like “tired” for them.
I’m looking for the study – I hope it didn’t just come out in a conference
Here the types are
‘Post-exertional fatigue (or malaise)’ occurs after physical or mental exertion; it is considered a hallmark symptom of this disease.
‘Brain fog’ – involves having difficulty with words and concentration; it is considered a hallmark symptom of this disease
‘Wired But Tired fatigue’ – is characterized by low energy levels accompanied by a feeling of over stimulation
‘Molasses Fatigue’ – is characterized by a feeling of heaviness in the limbs
Only the last occurs in the population regularly
Thanks, Cort. I’d heard of 5 types but never seen them. “Molasses” is a new term to me but it describes some of my fatigue to a T and is picturesque enough for others to understand.
It sounds like the Lights should have used samples which were already classified by subgroup based on their earlier work following exercise challenge. One has to wonder whether having the ME/CFS samples already divided into the a-2A increase vs. a-2A decrease subgroups which were previously described by the Lights would have made the results from this study more stratified.
Studying ME/CFS patients as one undivided group is like having a bowl full of little Halloween chocolate candy bars in the dark- they’re all the same size with the same type of wrapper but some are Nestle Crunches, some are plain Hershey’s milk chocolate, some are Hershey’s dark chocolate, some are Mr. Goodbars, etc. You’re never going to figure out what the ingredients are without grouping like with like.
“There was also a distinct separation into two groups within the CFS cohort based on the gene expression results. Thirty-four (71%) of the CFS patients had increases in the alpha-2A (α-2A) receptor at one or more time points following exercise, while 14 (29%) demonstrated large decreases in the same receptor. The larger subgroup showed large increases in eight genes but the smaller subgroup did not have signficant changes in any of these other genes compared to the control group.”
“α-2A Increase Subgroup (34/48 CFS subjects): This group exhibited large gene expression increases after exercise in the following genes: P2X4, P2X5, TRPV1, α-2A, β-1, β-2, COMT and IL10.”
“α-2A Decrease Subgroup (14/48 CFS subjects): The majority of this group (71%) also had clinical orthostatic intolerance and “suggests that different mechanisms cause the debilitating fatigue in this subgroup. The large decreases in α-2A may reflect a particular type of dysregulation of the sympathetic nervous system.”
Exercise Challenge Reveals Potential CFS Biomarkers-
Forgive me Cort, but I just discovered this website. It is late in the afternoon and I have been reading about the passing of Thomas Hennessey Jr. Firstly my attention was caught by his insistence on the naming of the illness “ME” I was further pulled in by the fact that he had chosen May 12 th (I knew why that date had been chosen) However, I was totally involved when I saw Dr. Byron Hyde`s name and the Nightingale Foundation mentioned. I was initially diagnosed in 1988 by Epstein-Barr testing but when I found myself living in Ottawa, Ontario, Canada and knew of the Nightingale Foundation, I made an appointment to see Dr. Hyde. He himself had ME I was given an appt with his colleague, a recent graduate from the University of Ottawa who tested and diagnosed using CDC guidelines and a brain scan. Dr. Jain shortly thereafter began his own practice and I followed him. At that time, the `treatment` was Prozac. I used it for a while and had Tyelenol 2 prn for headaches. I soon developed sleeping difficulties and started Zoplicone (Ambien) I moved about a 6 hour drive from Ottawa in 1995 and a family doctor took over my medical regime. I made one trip back to see Dr. Jain to find that he had decided to focus less on ME patients and more on HIV/AIDS patients He had explained to me that the thinking at that time was that ME was a retrovirus similar to HIV/AIDS or Leukemia and that I would have periods of ‘remission’ and times when I would ‘crash’. In the last 18 years I have been in ‘denial’, given ‘in’, been angry, but have never beat ME. However, in 2003 I had aggressive triple negative breast cancer. I had surgery for a tangerine size tumour, second surgery for 16 lymph nodes (all negative) chemotherapy with adriamyicin ‘push’ and 16 radiation treatments (experimental to give the same amount of radiation as normally given in 25 treatments) Ten years later I am cancer free………
Now, my question (I am also hyperverbal) Did any of the people in the test group have ME fog and Post Cancer fog so that they could compare themselves? Of course I ask that question because I can tell you that I have experienced both (post cancer only once thank goodness)
Thank you for reading this long post, but I think I will be following your post very carefully. I do not see that I will be receiving treatment for my ME but I hope that I can watch the progress that occurs over the next 20 years.
ME/CFS and then a huge cancer…They beat cancer -thank goodness. I wish they’d spend 1% of what they spend on cancer on ME/CFS.
To my knowledge no one has investigated if the cognitive difficulties are the same or different in ME/CFS and post-cancer fatigue. If I remember I’ll look to see if cognitive testing has been done in post-cancer. In ME/CFS the cognitive problems usually consist of problems with short-term memory, speed of information processing and executive functioning (planning/decision-making)…
The very first step in Yasko’s protocol is balancing glutamate and GABA via diet and supplements. So if that’s all that Lyrica does, who needs something that can cause life threatening allergic reactions or suicidal thoughts and actions?
Prostrate means lying face downward, not the male organ.
Are they saying that the genes are mutated so that they’re down or upregulated, or does their expression just change due to other (unknown) factors upstream? Where does methylation fit into this?
again does anyone have an interest or know someone who is interested in getting all facts together on illness from top cfs docs or top research? If I can get my hand on something substantial I will get it into the hands of a celebrity that may be able to get this disease out there and funded. So far no one responds. I don’t understand all you people who have abilities but are not getting back to doing real stuff. talking to each other on posts is fine but we need bid advocates. Come on people. we can be cause or effect. which one will we choose????
I wonder if post-cancer fatigue and ME/CFS could both be caused by toxic substances? Obviously, chemo is extremely toxic and I’ve had friends who have been through treatment and feel very similar to those of us with CFS.
About four months ago, a doctor tested me and my son for a number of things and found out we both had mold toxins in our bodies. This is what made me think of the toxin correlation in CFS and cancer patients.
Just curious – do cancer patients ever kick the fatigue? The people I know who went through treatment a couple years ago have not.
I believe that all sorts of cancer patients, including those undergoing chemotherapy, radiation, hormone treatment (as with this group) have problems with post-cancer fatigue. Who knows – maybe it is toxin buildup in some patients and something else in others.
Some post-cancer fatigue patients do kick the fatigue eventually. I’m not sure what percentage, though.
There is much more to DBI/ACBP than has been discussed.
Much more interesting than the GABA/glutamate sideshow, is that DBI/ACBP plays a key role in fatty acid metabolism and mitochondrial function.
As Marco said, you would expect elevated DBI, not reduced DBI for the GABA hypothesis.
Interestingly, DBI expression is not affected by exercise in mice/rats:
However psychological stress increases DBI expression (and thus would fit the GABA hypothesis in that case).
Thanks Snow Leopard. Good to see you again.
A GABA/Glutamate imbalance is a little more than a side show for patients with stiff person syndrome, alzheimer’s and ALS. In the latter, recent therapies are now focusing on attempting to stimulate glutamate transporters (including glial EAAT2) to clear extracellular glutamate (using some unexpected old friends).
As the Lights paper acknowledges and as I suggested above, reduced expression of DBI could be a homeostatic response to chronically low GABA or a glut/GABA imbalance.
I know you’re familiar with this paper :
A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis
and their working hypothesis that changes to mid brain and brainstem regions may be due to astrocyte dysfunction?
Astrocytes of course play a key role in glutamate regulation and extracellular glutamate clearance :
I’m open minded though. Another function of DBI is cholesterol transport and its role in steroidogenesis and mitochondrial function.
I posted a few links on your PR thread – ‘rhabdomyolysis’ – on the effects of cholesterol depleting statins.
Under-expression of DBI in ME/CFS patients would suggest reduced cholesterol transport with the associated knock on effects plus it would square with the frequent finding of raised cholesterol in ME/CFS.
Then of course a low energy neurological state due to mitochondrial dysfunction leaves the brain much more vulnerable to glutamate excitotoxicity which in turn can impact on mito function. So it all comes full circle.
Oh wow. My current research is to try to understand both post-cancer fatigue and chronic fatigue syndrome. I had what had to be CFS for some years when I was younger. Finally, gradually, over about 10 years, climbed out of the hole and was maybe 90 percent back. Then ten years later I found out I had breast cancer, stage IIIC, and had some very strong treatment. Smacked me into premature menopause. Have not gotten consistent energy back since then, seven years now, and more and more seems like I must be back in the CFS. Especially since I have the post-exertion malaise, among so many other things it has been hard to sort out as to what they are from–the PCF, the CFS, the sudden menopause, all the stress, the many other medical issues that cropped up since cancer treatment, several surgeries, infections, etc, or the PTSD that finally surfaced badly. LOL, if it sounds like too much to be true, try living it. But, I would so submit to testing to find out what is going on at a genetic level, if there could be answers found there, regarding if I have PCF, CFS, or both. I am thinking I have both.
Post cancer fatigue is actually very common and looks very much like CFS. If you had ME/CFS pre-breast cancer I wouldn’t be surprised if it showed up post-breast cancer…..