Instead of ME/CFS, could some have simple schizophrenia? Its symptoms: anhedonia, blunted emotions, brain fog, apathy, social withdrawal

[Mary]

@Hip - when my phosphorous is low, my mood nosedives. Nothing appeals to me and I just feel flat and empty. It's horrible, as you said. I think this fits the description of anhedonia and blunted emotions.

This happened to me just recently. I didn't know what was going on - I could remember having feelings but felt nothing. And then fortunately some pills got caught in my throat (thank goodness for all the pills I have to take!) and I realized my phosphorous had dropped. Trouble swallowing pills and double vision are warning signs for me of low phosphorous. Hypophosphatemia weakens all the muscles but affects the small muscles first. I have had hypophosphatemia causing severe overall fatigue - this is before I knew what it was or how to identify it.

Anyways, within a few hours of taking my phosphorous supplement, my mood improved, just like that. Suddenly I wanted to be alive again. I was very relieved and also rather amazed at what a big difference it made.

If you wanted to experiment with phosphorous, you might try what I did when I first learned about this, and that was to drink several glasses of kefir. At the time I had severe fatigue after taking thiamine (after initial energy boost). The fatigue was so severe, I'm sure I didn't notice my mood at all. Anyways, the kefir, high in phosphorous, caused the fatigue to start lifting within a few hours and I later found a phosphorous supplement.

 

[Hip]

Anyways, within a few hours of taking my phosphorous supplement, my mood improved, just like that.

Interesting, I've got a phosphorous supplement in stock, so I can try it.

Generally, it's very hard to treat anhedonia. Whereas there are hundreds of drugs and supplements that can treat depression, there is almost nothing available for anhedonia.

But some things that I found that improve anhedonia slightly are listed in this post.

 

[Mary]

@Hip , I had to take 100% of the RDA of phosphorus when my mood was so flat and pills were getting stuck in my throat. Often I just need 40 or 60% of the RDA. I use muscle testing to determine how much I need, I know, not scientific, but it works pretty well for me!

 

[Hip]

A recent randomised trial in patients with depression showed that the oral supplementation of Palmitoylethanolamide has beneficial effects on anhedonia and amotivation https://www.sciencedirect.com/science/article/abs/pii/S0165032717324278?via=ihub

This look interesting, I've never tried palmitoylethanolamide (PEA).

Though I did try phenylethylamine (found in chocolate), which is also abbreviated to PEA.

 

[hapl808]

I recently heard about palmitoylethanolamide and have been considering trying it. More and more I'm starting to think that a lot of my muscular problems are immune related (like the immune system attacking the myelin sheath similar to MS), so antihistamine or mast cell related drugs are interesting to me. Unfortunately the ones I've tried haven't worked or led to severe rebound when discontinued.

 

[datadragon]

This look interesting, I've never tried palmitoylethanolamide (PEA).

Though I did try phenylethylamine (found in chocolate), which is also abbreviated to PEA.

Palmitoylethanolamide (PEA) is a substance that is naturally produced in the body and available over the counter as a supplement (micronized is what you are looking for). And yes, not to be confused with another supplement phenylethlamine, which is also abbreviated as PEA for others who read this. PPAR-a activation using Palmitoylethanolamide (PEA) reduced the expression of pro-inflammatory cytokines at hippocampal, serum, and colonic level, reduction of leaky gut and beneficially restructured the gut microbiome, reversed autism behavior in mice, restored hippocampal BDNF signaling pathway, improved mitochondrial dysfunction, has helped with ibd in other studies. https://www.sciencedirect.com/science/article/pii/S0889159118305488

The impression I get is that in an inflammatory phase it can be quite helpful to bring that down and engages Allopregnanolone a progesterone metabolite to tamp down the inflammation as mentioned in my post. One of the suggested things to try therefore in a current inflammatory state. However some with ME/CFS enter a later stage where they are not producing energy properly and stuck in an anti inflammatory IL-10 state getting fatigue once there is no longer immune activation and that state requires a different approach, perhaps sodium butyrate can jumpstart the energy and restore TH1 balance.

 

[Wishful]

I don't think the substance itself is the real reason of the corresponding improvement in those cases but the expectation of some new experience and true belief that this one might work.

My effective treatments were all surprises. Two were prescribed treatments, but only on the "try this and see if it does anything", not "this should be really effective". I didn't expect curry to be a treatment, and it wasn't a new experience either, but it turned out to have an effect. The treatments that gave temporary full remissions were complete surprises.

I tried lots of things that either I had some belief they might work, and many things that were new experiences, but none of those had any effect.

 

[Murph]

From my personal experience, expecting something new and pleasant improves my condition a lot.

This is a fascinating insight! A dopamine-based (partial) mechanism in for me/cfs could even explain why people say they sometimes feel better when they travel / go on holiday. The dopamine rush of all the novelty might kick the body out of its diseased state (cell danger response/activated innate immune system/whatever) temporarily.

I remember feeling a lot better when I started a new job once. For the first 3 months in that role I was able to jog, even. Eventually working full time nearly killed me though!

Imagine if a feedback loop that contributed to the perpetuation of the disease was that locking yourself in your room to manage your *physical* symptoms (which is often necessary!) also created a dopamine rush shortage that worsened the immune situation. (nb we don't get the luxury of symmetry in this disease: i'm not saying ignoring the physical conditions and getting out there would cure you!)

Now, I don't think this is likely to be a big part of the explanation for most people, and I reckon it's likely to be downstream not upstream (e.g. infection -> gut dysbiosis -> lack of dopamine; or epithelial cell dysfunction -> lack of dopamine.)

But what I really really like about it is the sharing of a novel person insight (clear observation being the most important skill in science!) that could inform a plausible theory. Seeing our symptom patterns clearly is hard.

 

[Murph]

Two more notes on dopamine:
1. My doctor prescribed dexamphetamine, which seems to make me feel a lot better on the days I take it (it increases dopamine). But which I felt was also correlated with some lingering infections (sinuses, skin) so I stopped taking it for now. I intend to cycle back ont it.
2. Low activation of dopamine receptors seems to cause low muscle mass. I'm in the low muscle mass camp. And I perceive that when I do build some precious muscle mass my body will catabolise it rapidly during any PEM!

 

[Vladimir]

This is a fascinating insight! A dopamine-based (partial) mechanism in for me/cfs could even explain why people say they sometimes feel better when they travel / go on holiday. The dopamine rush of all the novelty might kick the body out of its diseased state (cell danger response/activated innate immune system/whatever) temporarily.

I remember feeling a lot better when I started a new job once. For the first 3 months in that role I was able to jog, even. Eventually working full time nearly killed me though!

Imagine if a feedback loop that contributed to the perpetuation of the disease was that locking yourself in your room to manage your *physical* symptoms (which is often necessary!) also created a dopamine rush shortage that worsened the immune situation. (nb we don't get the luxury of symmetry in this disease: i'm not saying ignoring the physical conditions and getting out there would cure you!)

Now, I don't think this is likely to be a big part of the explanation for most people, and I reckon it's likely to be downstream not upstream (e.g. infection -> gut dysbiosis -> lack of dopamine; or epithelial cell dysfunction -> lack of dopamine.)

But what I really really like about it is the sharing of a novel person insight (clear observation being the most important skill in science!) that could inform a plausible theory. Seeing our symptom patterns clearly is hard.

Thanks for sharing this similar experience. I agree, it is very important and helpful to gather more common feedback to better understand this desease.

I definitely feel better both when I am out for the trip to another country and when I am back home. The sad part is that both works for an extremely limited amount of time - sometimes a week, sometimes a couple of days. Being in the same environment, knowing 100% what your next 24 hours will look like - all that flattens our dopamine level. And paradoxically, our physical exhaustion does not allow us to break this vicious circle.

As for downstream/upstream, I would prefer it to be downstream too so that there is some relatively easy to study and manageable root cause. But so far I could not find any evidence for that. It is other way around actually - all those differences in various infections, viruses, physical pathologies like chiari malformation etc., the nuances of how ME/CFS manifests in different people in general - all that tells me that the brain biochemistry (dopamine, maybe other stuff) is the real cause.

We are just more susceptible to stress, we need more excitement and new stuff in our life than others. And when life challenges us (which it does to everyone starting from a certain age - another reason that children do not get ME/CFS) our bodies start to ache and loose all of the energy instead of having a typical depression of other mental issues.

I really want to be wrong about that and still hope for a scientific breakthrough, but the more I live with CFS the more I understand that the only way to cope with it is to focus on those rare moments where you felt more or less good, analyze and try to recreate it.

 

[Vladimir]

Recently, I found an interesting video about two brothers who get paralysed when sun goes down.

Although they (quite) successfully treated those boys with L-Dopa which directly increases dopamine levels, YouTube commenters suggested the real cause was hypokalemic nighttime muscle paralysis https://en.wikipedia.org/wiki/Hypokalemic_periodic_paralysis - a genetic desease.

It has a lot of similarities with CFS. According to Wiki: "attacks... occur with individual triggers such as rest after strenuous exercise (attacks during exercise are rare), high carbohydrate meals, meals with high sodium content, sudden changes in temperature, and even excitement, noise, flashing lights, cold temperatures and stress"

Who knows, maybe CFS relates to this case somehow.

 

[crussher]

In response to the OP about schizophrenia, I just came across a paper from 1937 which examined blood volume levels in schizophrenic patients. It really brought me up short - it found that the schizophrenics had around 12.5% less total blood volume than normal and 20% less plasma volume - really the same as what is often seen in ME/CFS.


I know there have been a few threads on PR talking about possible links between ME and schizophrenia particularly in terms of some shared psychological traits (but not all) but this 1937 paper made me wonder if some people diagnosed with schizophrenia, historically and now, have actually had ME/CFS and were struggling with personality changes simply because of low cerebral perfusion.


I couldn’t find any paper since then looking at blood volume levels in schizophrenic patients.


The original article is behind a paywall but here is a short contemporaneous write-up of the paper from one year later - note how the supposed reasons for the low blood volume also are, albeit in a 1938 kind of language, really reminiscent of ME/CFS also:


‘The writers found a low circulating blood volume in patients with schizophrenia, as compared with manic-depressive patients, whose circulating blood volume approaches normal. The schizophrenics had a blood volume per square metre of body surface of 2,609 c.c., as compared with 2,973 c.c. in manic-depressive patients. The plasma volume in schizophrenia per square metre of body surface was 1,433 c.c., as compared with 1,727 c.c. in the manic-depressive patients. The diminution in the circulating blood volume in schizophrenia appears to be related to disturbances in water metabolism, capillary permeability and vasomotor tonus, secretion of the antidiuretic and vasopressor hormone of the posterior pituitary gland, basal oxygen consumption rate and indirectly heat regulation. These failings may be due to dysfunction of the hypothalamus. The circulating blood volume in involutional psychoses was lower than in schizophrenia.’[1]


Would be interested in people’s thoughts. I think this raises a lot of questions.

 

[Mary]

A dopamine-based (partial) mechanism in for me/cfs could even explain why people say they sometimes feel better when they travel / go on holiday. The dopamine rush of all the novelty might kick the body out of its diseased state (cell danger response/activated innate immune system/whatever) temporarily.

This has never happened to me. I crash regardless of whether I get to do something I really like to do (like travel to see kids and grandkids) or doing what I have to do (grocery shopping). Doing something I like has never boosted my energy levels or prevented crashing. Actually, it makes things worse! Because I'm more likely to over-exert myself (and thus crash) if I'm doing something I actually want to do, which happens all too rarely with this insane illness.

I hate to say it, but your theory sounds awfully similar to what people like Wessely et al. have been saying for decades - if only we changed our thinking! we might get better.

Anticipating something novel, again, has never prevented me from crashing. Sure - it might boost my mood a bit but it changes nothing else for me. All it does is increase the likelihood that I will crash in the near future if I elect to do what I want to do (explore the novelty) instead of playing it safe and not doing so, to avoid crashing. Every day of my life is an exercise in balancing what I want/need to do, how much energy I can expend on any one thing, all trying to avoid crashing, and also all dependent on the amount of energy that may be available to me that day, which often is not very much. Though sometimes I throw in the towel - if kids or grandkids are coming to visit, I don't care that I will crash the next day. This is a very cruel disease, and I'm considered moderate, though it has stopped me from living my life in any meaningful way.

 

[hapl808]

Doing something I like has never boosted my energy levels or prevented crashing. Actually, it makes things worse! Because I'm more likely to over-exert myself (and thus crash) if I'm doing something I actually want to do, which happens all too rarely with this insane illness

Same. I feel better on a trip for about 24 hours because I forget that I'm going to crash, then I feel awful for days (or sometimes weeks). It has ruined many trips for me because I ended up bedbound.

I hate to say it, but your theory sounds awfully similar to what people like Wessely et al. have been saying for decades - if only we changed our thinking! we might get better.

Anticipating something novel, again, has never prevented me from crashing. Sure - it might boost my mood a bit but it changes nothing else for me. All it does is increase the likelihood that I will crash in the near future if I elect to do what I want to do (explore the novelty) instead of playing it safe and not doing so, to avoid crashing.

Same. To each their own and all hypotheses are welcome, but I disagree 100%. Nothing described duplicates my experience. The more novel and enjoyable the activity for me, the worse the crash and the longer it tends to last. Back when I wasn't housebound or bedbound, sexual activity was probably the worst - would leave me crashed for days, mess up my digestion, etc. And that was pretty enjoyable.

Again - there's a tendency to project what we've experienced onto others, but that's often a bad fit. I don't know if my experience translates to anyone else, but I know for me how enjoyable or novel an activity is tends to make it worse, not better. Which is horrible because I'm the kind of person who loves exploring new things, places, etc. I traveled extensively when I was more mild, but I was also sick constantly because I continuously outpaced what I could do.

 

[Judee]

In response to the OP about schizophrenia, I just came across a paper from 1937 which examined blood volume levels in schizophrenic patients. It really brought me up short - it found that the schizophrenics had around 12.5% less total blood volume than normal and 20% less plasma volume - really the same as what is often seen in ME/CFS.

And in POTS too.

(Very good find @crussher!!)

 

[Wishful]

I was thinking about a couple of "novel, anticipating pleasure" events in my life: getting an e-reader, and a new computer. I don't remember any reduction in my ME symptoms those times.

New experiences might work for Vladimir, but maybe not for anyone else. Many of us have things that work for us and no one else.

 

[Vladimir]

New experience is just one example that can lead to dopamine level increase, it does not mean it will. Actually, in my opinion this might be the root of the illness - our dopamine system does not fire up when it is supposed too. For a "normal" person a simple walk can be a great source of dopamine. For us most of the "regular" stuff like getting a new toy, meeting an old friend etc. does not work anymore, and in most cases it just does the opposite - drains out energy...

 

[datadragon]

Both the selective Dopamine D1-like agonist, A-77636, and the D2-like agonist, quinpirole, also induced Fos in orexin cells, suggesting that stimulation of either receptor subtype is sufficient to activate orexin neurons. https://pubmed.ncbi.nlm.nih.gov/15978010/

Chronic Interferon-α Decreases Dopamine 2 Receptor Binding and Striatal Dopamine Release in Association with Anhedonia-Like Behavior in Nonhuman Primates https://www.nature.com/articles/npp2013115

When the gastroparesis was induced by the destruction of dopaminergic neurons in the substantia nigra SN, the decreased expression of dopamine receptor 1 D1 and Orexin A OXA was observed in the lateral hypothalamic nucleus LH as well as the reduced orexin receptor 1 OX1R and ChAT expression in the dorsal motor nucleus of vagus DMV. These findings suggest that SN might regulate the function of Orexin A-positive neurons via Dopamine Receptor 1, which then affect the motor neurons in the DMV through OX1R orexin receptor 1. https://pubmed.ncbi.nlm.nih.gov/30923496/ https://academic.oup.com/schizophreniabulletin/article/33/6/1277/1902355?login=false

Schizophrenia is associated with marked sleep disturbances and memory impairment. (areas also involved around orexin balance). We measured plasma hypocretin-1 (orexin) levels in Schizophrenic patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379539/

Orexin Modulation of VTA Dopamine Neuron Activity: Relevance to Schizophrenia. Aberrant dopamine system function in MAM-treated rats was normalized by the systemic administration of dual orexin antagonist TCS 1102. To investigate the potential site of action, the orexin peptides A and B were administered directly into the PVT, where they significantly increased ventral tegmental area dopamine neuron population activity in control rats. In addition, the direct administration of TCS 1102 into the PVT reproduced the beneficial effects seen with the systemic administration in MAM-treated rats. https://pubmed.ncbi.nlm.nih.gov/33587746/

Immunomodulatory Effects of Dopamine in Inflammatory Diseases (roles in inflammation/immune function) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063048/

​

 

[Wishful]

For us most of the "regular" stuff like getting a new toy, meeting an old friend etc. does not work anymore, and in most cases it just does the opposite - drains out energy...

That doesn't apply to me either. A brisk hike or bike ride--or new e-reader--doesn't drain me. It doesn't seem to affect my ME symptoms significantly. I think I get the same mental state as pre-ME, although that's too long ago to remember clearly.

I'm not sure what dopamine elevation feels like. Does a smile or laugh from a funny scene in a book count? Climbing a tall tree?

 

[hapl808]

New experience is just one example that can lead to dopamine level increase, it does not mean it will. Actually, in my opinion this might be the root of the illness - our dopamine system does not fire up when it is supposed too. For a "normal" person a simple walk can be a great source of dopamine. For us most of the "regular" stuff like getting a new toy, meeting an old friend etc. does not work anymore, and in most cases it just does the opposite - drains out energy...

I think there's significant evidence that dopaminergic drugs (receptor dependent) may impact ME/CFS symptoms for some (this has been discussed extensively with regard to LDA, etc), but to be honest it sounds more like you're trying to fit a very simplistic and inaccurate unified model of the dopamine system onto an illness where the etiology is completely unclear. The dopamine system may be involved, or serotonin, or noradrenaline, or glutamate. All of those are involved in a new experience, or enjoyable things, etc.

For me, fun new experiences give me lots of energy - very briefly and then lead to a horrific crash. The lengthy PEM crash and the permanent worsening of my symptoms afterward are the problem.

So yeah - none of that rings true for me, but it may absolutely ring true for you. Wishful and I also have different experiences from you, and different experiences from each other.

That's why the disease is complex and has eluded researchers for decades of study.