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

[Hip]

Simple schizophrenia is a type of schizophrenia that does not involve the classic schizophrenia symptoms of hallucinations, delusions, paranoia, false beliefs, incoherent thinking and confused speech (these are the so-called positive symptoms of schizophrenia).

Simple schizophrenia only involves the negative symptoms of schizophrenia, which include:

• Anhedonia (reduced ability to experience pleasure or reward from normally enjoyable activities)
• Blunted emotions
• Apathy
• Social withdrawal (lack of interest in social interactions and withdrawing from social contact)
• Reductions in speech
• Difficulty in concentrating during conversation, and an inability to concentrate on even simple tasks (ie, brain fog)

See: Negative Symptoms of Schizophrenia and Negative Symptoms in Schizophrenia.

So whereas regular schizophrenia involves both the positive and negative symptom sets, simple schizophrenia only has the negative symptoms.

Simple schizophrenia is also called deficit schizophrenia (or at least these two terms are closely related).



One recent study found that a subset of both simple schizophrenia and regular schizophrenia patients displayed symptoms reminiscent of ME/CFS and fibromyalgia — including fatigue, muscle pain, muscle tension, autonomic symptoms, and a flu-like malaise.

The study also found that such somatic symptoms in schizophrenia patients were associated with inflammatory cytokines like IL-1beta, TNF-alpha and CCL11.

So I am wondering whether cases of ME/CFS that involve symptoms such as anhedonia, blunted emotions, social withdrawal and apathy, might actually involve simple schizophrenia. If so, some of the treatments for simple schizophrenia (listed below) might help.



In my case, as well as the usual ME/CFS symptoms of fatigue, brain fog, PEM, POTS, unrefreshing sleep, gut issues, sound sensitivity, etc, I also experience anhedonia, blunted emotions and social withdrawal. So I can relate to some of the negative symptoms.

Also, I find that although I get PEM from mental exertion like socialising, I don't get much PEM from physical exertion. So that makes my ME/CFS more unusual.

Furthermore, I find low doses of the antipsychotic amisulpride helpful for my social withdrawal (my thread on amisulpride here), and amisulpride is effective against negative symptoms at low doses like 100 mg daily.

It's also interesting that some ME/CFS patients have experienced improvements from the antipsychotic Abilify (aripiprazole), which one study found improves negative symptoms.



Although simple schizophrenia is considered less severe than regular schizophrenia (because the former does not include the positive symptoms), it actually is harder to treat than regular schizophrenia, because negative symptoms "generally do not respond well to currently available antipsychotic treatment with dopamine D2 antagonists or partial D2 agonists". Ref: 1

However, there are some drugs and supplements which may improve the negative symptoms of schizophrenia:

Spoiler: Some Supplements and Drugs That May Help Negative Symptoms

Low doses of amisulpride (100 to 300 mg) or olanzapine (10 to 20 mg) beneficial for the negative symptoms of schizophrenia. Refs: 1 2

Maprotiline (tetracyclic antidepressant drug) improves the negative symptoms of schizophrenia by a noradrenaline potentiating action. 1

Agomelatine effective for negative symptoms. 1

COX-2 inhibitors like celecoxib help negative symptoms. 1

5-HT3 antagonists (ondansetron, tropisetron, granisetron) help negative symptoms. 1 2
Lemon essential oil is a potent 5-HT3 antagonist (beta-pinene content is a 5-HT3 antagonist).

5-HT2 antagonists (ritanserin) help negative symptoms. 1 List of 5-HT2 antagonists, includes mirtazapine.

Oxytocin shown particular promise to treat the intractable negative symptoms and social cognitive deficits. 1

N-acetyl-cysteine improves negative symptoms. 1

Sarcosine 1 to 2 grams daily beneficial for the negative symptoms of schizophrenia. 1

Carnosine reduces negative symptoms, but not positive. 1

Galantamine may be effective for negative symptoms. 1

Pregnenolone and DHEA improve negative symptoms. 1

Pregnenolone plus L-theanine for negative symptoms and anxiety. 1

.​

 

[hapl808]

Interesting. I wonder if that's a subset. Definitely don't think it applies to me since cognitive or social exertion gives me the same amount of PEM, and physical is probably even worse. Plus I still love doing stuff (talking on the phone, videochats, etc) but can't do them because I keep crashing afterward. That steals a lot of my day to day enjoyment because I can't pursue pretty much anything I enjoy and have to purposefully avoid the things I want to do - which leads to some social withdrawal and anhedonia I suppose. But doesn't sound like that's similar to what you're describing here.

 

[Rufous McKinney]

Comment: I have my baby granddaughter here visiting for the last five months.

I can testify that I am here smiling at her all the time. She makes me smile and laugh, makes me happy, she glows.

All that oxytocin should have cured something by now.....

 

[Rufous McKinney]

That steals a lot of my day to day enjoyment because I can't pursue pretty much anything I enjoy and have to purposefully avoid the things I want to do

that is entirely the same here. I can be highly motivated to desire to do "something" but I can't let myself: I'll just crash. Over and over again, I think I won't crash and I do, anyway.

And it still surprises me, when it happens.

don't think it applies to me since cognitive or social exertion gives me the same amount of PEM, and physical is probably even worse.

yeah- physical has more delay and lasts longer I think...

 

[Hip]

I can't pursue pretty much anything I enjoy and have to purposefully avoid the things I want to do - which leads to some social withdrawal and anhedonia I suppose.

If you have to avoid activities because of the PEM and fatigue repercussions, I would not called that anhedonia or social withdrawal.

Anhedonia is the most horrible symptom, especially when it gets severe. You spend the whole day trying to find something simple to do that might stimulate a modicum of enthusiasm, interest or enjoyment, but nothing at all creates any spark of enthusiasm or enjoyment. Most people have experienced the occassional day when they feel ennui, listless or fed up. But full-blown anhedonia is incomparably worse.

In healthy people, even tidying your desk or reading a newspaper brings some small enjoyment and satisfaction; but with anhedonia your brain's pleasure and reward circuits are almost dead, so you live in the most inhuman void of zero enjoyment. Nothing satisfies. Fortunately my anhedonia is only mild these days, and no longer severe.

With social withdrawal, not only do you dislike socialising, but the whole realm of human interaction seems, in your mind, to be somewhat alien and incomprehensible. So you don't like to talking to people, and you cannot see the need to do so either. Again it is a most inhuman void.



Anhedonia and social withdrawal are not normal symptoms of ME/CFS, so I think most ME/CFS patients will not relate to these symptoms (although blunted emotions is a common ME/CFS symptom, listed in the CCC, so many patients will understand this).

 

[hapl808]

Maybe blunted emotions is a better description. I haven't left the house in years, so it's a bit hard to relate to the outside world other than in my memories. My problem is that there are things I enjoy, but I can do almost none of them. Can't really listen to music, only can watch things that aren't too stimulating, reading long form stuff has gotten tougher, etc. Still, I think it's a far cry from anhedonia as you describe it. Kinda like when I can tell doctors want me to say I'm depressed, but I don't think I am. I would be on a plane tomorrow and having fun if I were magically cured. People I've known who suffer from depression - are depressed almost independent of their life events. That's what makes it so hard to treat. It has very little to do with their circumstances and more to do with their emotional keel. But doctors are always like, "Wow, this sounds very limiting. How has that been on your mental health?" Umm, pretty tough - mainly because I have to deal with idiotic doctors a lot.

 

[Wishful]

Umm, pretty tough - mainly because I have to deal with idiotic doctors a lot.

Well, that put a smile on my face.

As to the question of the thread, I certainly think that there will be quite a few people who get diagnosed with ME who actually have some other disorder, such as schizophrenia of whatever type. A more interesting question to me is whether they share a mechanism. Research into ME's mechanisms might provide answers for many other disorders. That should be emphasized more in funding requests for ME research.

 

[hapl808]

A more interesting question to me is whether they share a mechanism. Research into ME's mechanisms might provide answers for many other disorders. That should be emphasized more in funding requests for ME research.

Yeah, my guess is we'll find a lot of disparate disorders are all connected to some initial insult, gut biome disruption, autoimmune illness, etc. Wouldn't be surprised if research in the future shows that one person's depression is connected to a herniated disc at 12 years old, another person's borderline diagnosis is connected to a food borne illness contracted at 16 years old, and so forth.

 

[Hip]

Maybe blunted emotions is a better description. I haven't left the house in years, so it's a bit hard to relate to the outside world other than in my memories.

Blunted emotions are very evident even just watching TV. I find with my blunted emotions, I don't get into any melodramatic TV movies, like say a romantic film. Whereas previously I would have enjoyed and related to such things. So you don't necessarily need to leave the house and have an active social life to observe your blunted emotions ("blunted affect" as it is technically called in psychiatry).


Note that people often confuse anhedonia with blunted emotions, but they are different (although they often come together as a package). With blunted emotions, normal emotional experiences (love, sadness, anger, guilt, compassion, jealousy, etc) are weakened or absent.

With anhedonia, it is the feeling of pleasure or reward from doing an activity, or from anticipating an activity, which is weakened or absent.

The main two mental health conditions where you can find anhedonia as a sub-symptom are depression and schizophrenia. Depression may or may not involve anhedonia, but when it does, it's much worse, and also it tends to become treatment resistant (does not respond much to antidepressant drugs).

 

[datadragon]

Lots of overlap...

Depression:

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

Palmitoylethanolamide (PEA) which activates PPAR-a also showed antidepressant effects. These effects were mimicked by the PPAR-a synthetic agonists, and the antidepressive effects of PEA were prevented by PPAR-a deletion + antagonists https://www.sciencedirect.com/science/article/abs/pii/S0165032718315994 PPAR agonists (activators) have been shown to decrease IL-1 expression by deregulating caspase-1 and NLRP3 https://www.pnas.org/content/116/49/24819 Antidepressants also lowered NLRP3, IL-1b and IL-18 https://img.auctiva.com/imgdata/1/9/6/8/1/0/0/webimg/1078908000_o.png

There is a consistent decrease in the levels of physiologically active progresterone metabolite allopregnanolone in limbic brain areas in rodents submitted to stress-induced models of depression, such as social isolation and chronic unpredictable stress. Further, both the drug-induced upregulation of allopregnanolone or its direct administration reduce depressive-like behaviors in models such as the forced swim test. Brain-derived neurotrophic factor (BDNF) is decreased in animal models of depression and may be restored by the normalization of allopregnanolone levels https://www.sciencedirect.com/science/article/pii/S2352289520300084

PPARa activation by using Palmitoylethanolamide (PEA) engages Allopregnanolone biosynthesis and induced marked antidepressive- and antianxiety effects. The naturally occuring neurosteroid progesterone metabolite allopregnanolone prevents the activation of pro-inflammatory proteins important for gene regulation, as well as the creation of cytokines, which are known to be involved in many different inflammatory conditions. Allopregnanolone also tamps down chemokines and cytokines, such as NFkB, HMGB1, MCP-1 and TNF-a, all of which are part of the immune system and involved in many different inflammatory diseases. Allopregnanolone substantially blocked, or inhibited, the LPS-induced TLR4 activation in macrophages, which are found in white blood cells and part of the immune system, including in the brain. In macrophages, the TLR4 protein is part of a proinflammatory response that leads to the production of pro-inflammatory cytokines https://www.sciencedirect.com/science/article/pii/S0006322319300812

Both the drug-induced upregulation of allopregnanolone or its direct administration reduce depressive-like behaviors in models such as the forced swim test. Brain-derived neurotrophic factor (BDNF) is decreased in animal models of depression and may be restored by the normalization of allopregnanolone levels https://www.sciencedirect.com/science/article/pii/S2352289520300084

Zinc increases the gene expression of A20 and PPAR-a, the two zinc finger proteins with anti-inflammatory properties and all PPAR agonists tested lost their potency to downregulate the TNF-induced inflammatory response in zinc-deficient cells. However, if zinc was added back, all PPAR agonists significantly downregulated the TNF-mediated induction of inflammatory transcription factors NF-B and AP-1 and significantly reduced the expression of their target genes, VCAM-1 and IL-6. https://academic.oup.com/jn/article/134/7/1711/4688619

Those who are 'extra happy' people naturally produce less of the enzyme FAAH (fatty acid amide hydrolase). In fact, a strong correlation was found between a nations and persons happiness and having the A allele in the FAAH gene variant rs324420 that helps prevent the chemical degradation https://www.sciencedaily.com/releases/2016/01/160114113520.htm Inhibitors of the enzyme fatty acid amide hydrolase (FAAH) increases endogenous levels of anandamide (a cannabinoid CB(1)-receptor ligand (activator)) and oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), activators for PPAR-alpha.

CB1R activation results in decreased release of glutamate in glutamatergic synapses https://www.nature.com/articles/s41398-021-01612-3

Excessive glutamate and subsequent over-stimulation of Glutamate NMDA receptors leading to excessive Ca2+ (Calcium influx) as NMDA NR2B is the receptor linked to depression when increased (and decreased by zinc https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077707/ and ketamine https://pubmed.ncbi.nlm.nih.gov/33981335/ for example), but this is also a receptor for memory & learning. Both mice and rats that were engineered to over-express GRIN2B in their brains have increased mental ability. The "Doogie" mouse had double the learning ability on one measure of learning. age-related decreases in the NMDA NR2B subunit correlate with memory deficits. Highly intelligent and depressed...

Both SSRI fluoxetine and tricyclic desipramine are able to inhibit the GluN2B subunit-containing NMDA receptors in low micromolar concentration range as another example. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816696/

Serotonin, by activating 5-HT(1A) 5-hydroxytryptamine receptor 1A receptors, inhibited NMDA receptor-mediated ionic and synaptic currents in PFC pyramidal neurons, and the NR2B subunit-containing NMDA receptor is the primary target of 5-HT(1A) receptors. Inhibition of either CaMKII (calcium/calmodulin-dependent kinase II) or MEK/ERK (mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) abolished the 5-HT(1A) modulation of NMDAR currents. https://pubmed.ncbi.nlm.nih.gov/15944377/ Activation of 5-HT2A/C receptors counteracts 5-HT1A regulation of n-methyl-D-aspartate receptor channels in pyramidal neurons of prefrontal cortex https://pubmed.ncbi.nlm.nih.gov/18442977/

. The mRNAs of NR1 and NR2A subunits were significantly decreased by orexin-A and orexin-B at concentrations over 0.1 microM and 0.01 microM, respectively. The mRNA expression of NR2B subunit was also significantly decreased by orexin-A and orexin-B only at the concentration of 1 microM. Moreover, orexin-A and orexin-B at concentrations over 0.01 microM significantly decreased the mRNA expressions of AMPA receptor subunits, GluR1 and GluR2. https://pubmed.ncbi.nlm.nih.gov/18573570/

The type 1 cannabinoid receptor (CB1R) and both subtypes of the orexin receptor, orexin receptor type 1 (OX1R) and orexin receptor type 2 (OX2R) are not only expressed in the same brain regions modulating these functions, but physically interact as heterodimers in recombinant and neuronal cell cultures. Moreover, cannabinoid-orexin receptor interactions are sex-specific with regards to brain region and functionality. https://pubmed.ncbi.nlm.nih.gov/34992518/

Vitamin B6 increased the protein levels of N-methyl-D-aspartate receptor (NMDAR) 2B, postsynaptic densities (PSDs) protein 95, and calmodulin-dependent protein kinase II (CaMK-II) in the hippocampus, which were decreased by isocarbophos in rats. Administration of vitamin B6 increased the blood flow in the right and left posterior cerebral arteries and improved the functions of learning and memory in isocarbophos-treated rats. Morphological analysis by light microscope and electronic microscope indicated disruptions of the hippocampus caused by isocarbophos were normalized by vitamin B6. Importantly, the antagonist of NMDAR signaling by eliprodil abolished these beneficial effects produced by vitamin B6 on PCA blood flow, learning, memory, and hippocampus structure in rats, as well as the protein expression of NMDAR 2B, PSDs protein 95, and CaMK-II in the hippocampus. https://pubmed.ncbi.nlm.nih.gov/28872356/

 

[datadragon]

PPAR-α controls calcium influx and the expression of several genes coding hippocampal proteins involved in regulation of synaptic plasticity. PPAR-α is engaged in expression of N-methyl-D-aspartate (NMDA) receptor subunit NR2A and NR2B genes. All these mentioned genes are related to synaptic plasticity and are regulated by PPAR-α via cyclic AMP response element binding protein (CREB). PPAR α- null mice are deficient in CREB and memories associated proteins and have decreased spatial learning and memory. PPAR-α exerts neuroprotective effect by regulating the level of kynurenic acid (KYNA) an endogenous glutamate receptor antagonist https://link.springer.com/article/10.1007/s11064-020-02993-5

High homocysteine following folic acid or vitamin B12 deficiency also down-regulates peroxisome proliferator-activated receptor (PPAR) expression. Homocysteine has recently been found to be a competitive inhibitor of the nuclear transcription factors: Peroxisome proliferator activated receptors (PPARs) alpha and gamma https://link.springer.com/article/10.1186/1475-2891-3-4 Homocysteine activated NLRP3 inflammasomes in THP-1-differentiated macrophages and promoted subsequent production of IL-1β and IL-18 in macrophages, which were blocked by NLRP3 gene silencing or the caspase-1 inhibitor Z-WEHD-FMK https://pubmed.ncbi.nlm.nih.gov/28394319/ It has been reported that homocysteine activates glutamate receptors by acting as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor. Thus, overactivation of the glutamate receptors leads to increased intracellular calcium levels and further activation of signaling kinases resulting in neurodegeneration and neuronal damage through a process called excitotoxicity https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-016-0241-8

reduced plasma levels of vitamin B12 and DHA and increased homocysteine levels were also observed in schizophrenic patients https://www.sciencedirect.com/science/article/abs/pii/S0165178109000225?via=ihub

Dopamine binding to D1 receptors enhances the excitatory effects that result from glutamate’s interaction with a specific glutamate receptor subtype (i.e., the NMDA receptor). Conversely, activation of D2 receptors inhibits the effects induced by glutamate’s binding to another glutamate-receptor subtype (i.e., the AMPA receptor https://www.sciencedirect.com/science/article/abs/pii/S0006899312005112 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826820/

We measured orexin-A in the cerebrospinal fluid (CSF) of 66 patients with major depressive disorder (MDD), dysthymia and adjustment disorder after a suicide attempt. Blood samples confirmed that the patients were free from antidepressive and neuroleptic medication at the time of the lumbar punctures. CSF levels of orexin-A were significantly lower in patients with MDD than in patients with adjustment disorder and dysthymia. https://pubmed.ncbi.nlm.nih.gov/17346943/ On a side note, In clinical studies, a dose-dependent increase in suicidal ideation was observed in patients taking BELSOMRA so looks like low levels of orexin may be involved. https://www.merckconnect.com/belsomra/mechanism-of-action/

@Hip Hope this is helpful.

 

[Vladimir]

By now, I strongly believe that CFS/ME is an illness caused by dopamine imbalance/misregulation.

Abilify which is a dopamine modulator and helps many people here supports that notion well.

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

So, for some people dopamine issues cause schizophrenia and corresponding mental manifestations, and for us it mostly leads to physical impairment and sometimes minor mental problems too.

 

[Wishful]

By now, I strongly believe that CFS/ME is an illness caused by dopamine imbalance/misregulation.

No, I think it more likely means that dopamine imbalance might be a downstream effect causing symptoms in some people. It seems less likely as a root cause. It seems more likely that immune activation triggers some sort of positive feedback loop involving the immune systems, locking us into an abnormal state. That might include glial dysfunction, which creates neural dysfunction, which overall could cause dopamine imbalance.

Does Abilify reduce all ME symptoms and responses, or just reduces one or a few? The latter implies an effect downstream of the core dysfunction.

 

[datadragon]

By now, I strongly believe that CFS/ME is an illness caused by dopamine imbalance/misregulation. Abilify which is a dopamine modulator and helps many people here supports that notion well.

No, I think it more likely means that dopamine imbalance might be a downstream effect causing symptoms in some people. It seems less likely as a root cause. It seems more likely that immune activation triggers some sort of positive feedback loop involving the immune systems, locking us into an abnormal state. That might include glial dysfunction, which creates neural dysfunction, which overall could cause dopamine imbalance.

Both are accurate to a point. Dopamine also interacts with Orexin neurons also as I mentioned here (and below) https://forums.phoenixrising.me/thr...nfa-itaconate-shunt-part-2.89388/post-2438443 but if you look at some of the other research I've temp put in that thread and a few others to start piecing the puzzle pieces together there are other pathways that also lead to orexin balance. The cytokines alone such as Tnf-a and INF-a are known to reduce orexin but could also induce a more serious phase we are seeing in later stages. The cytokines could induce IDO1 and kill orexin neurons while making dendritic cells produce more anti inflammatory il-10 in a irreversible manner that doesnt resolve once there is no longer immune activation. https://forums.phoenixrising.me/thr...ed-abnormalities-in-me-cfs.90173/post-2437768 TNF-a also increases at a delay from 8-24 hours.

Orexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to corticolimbic sites and subserve psychostimulant-induced locomotor activity. We examined the ability of dopamine agonists to activate orexin neurons in the rat, as reflected by induction of Fos. The mixed dopamine agonist apomorphine increased Fos expression in orexin cells, with a greater effect on orexin neurons located medial to the fornix. Both the selective 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/

 

[hapl808]

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

I think dopamine is involved, but hard to say if it's a symptom or a cause. New and pleasant improved my condition when I was very mild - now it makes me much worse. Anything that is engaging (a fun phone call, an interesting computer task) will cause me to crash.

 

[Vladimir]

I think dopamine is involved, but hard to say if it's a symptom or a cause. New and pleasant improved my condition when I was very mild - now it makes me much worse. Anything that is engaging (a fun phone call, an interesting computer task) will cause me to crash.

I believe it has to be something really new and exciting to get a dopamine boost.

Another example that led to my conclusion was the fact that almost all of us, including me, got some temporary benefit from a lot of different stuff like arbitrary vitamins, mineral supplements, or a new diet etc.

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.

 

[Vladimir]

No, I think it more likely means that dopamine imbalance might be a downstream effect causing symptoms in some people. It seems less likely as a root cause. It seems more likely that immune activation triggers some sort of positive feedback loop involving the immune systems, locking us into an abnormal state. That might include glial dysfunction, which creates neural dysfunction, which overall could cause dopamine imbalance.

Does Abilify reduce all ME symptoms and responses, or just reduces one or a few? The latter implies an effect downstream of the core dysfunction.

Abilify as well as a more modern version of the same group of drugs called Cariprazine worked very well for me. I was 100% functional during 7-10 days, I slept well, no food cravings etc.

But I had to stop pretty soon due to severe akathisia - something that is very hard to explain, quite a unique condition that after several days become a reason to stop the experiment completely

 

[hapl808]

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.

Not my personal experience, mainly because what has helped me has been such a small gain as to be almost unnoticeable (with the exception of antibiotics taken for a totally different condition and a complete surprise), is usually sustainable, but doesn't seem correlated with what I think will work. I have a lot of muscular weakness and I really thought testosterone would help after months of research. It almost completely crippled me.

The problem is that we project our own experiences onto others, but ME/CFS has so many different flavors. One person is mostly gut related, another might be mostly cognitive triggered PEM, another only physical exertion triggered PEM, another does well on carnivore, another does well on vegan, and so forth.

It's all guesswork, and mostly we're just doing N=1 science. I have no clue what the real etiology might be, or whether there will be a unified theory or we'll find that we're calling 30 different diseases all ME/CFS. Imagine if we didn't understand bacteria or viruses - all infections might look the same, but one person gets skin lesions and another has breathing problem and another starts losing weight...

 

[Rufous McKinney]

Blunted emotions

in my case this illness intensifies emotions. Then I have to cut them off, feeling them intensely because that makes me more ill.

getting angry feels REALLY awful. I can cry easily but that seems to cause almost instant PEM.

But everything that is an activity I once enjoyed I feel little or no enjoyment in it.

Definately something is biochemically altered.

 

[Rufous McKinney]

Anything that is engaging (a fun phone call, an interesting computer task) will cause me to crash.

The "is it even worth it" ? syndrome.