Review Chronic stress and cognitive dysfunction in [ME/CFS]: HPA axis dysregulation and hippocampal plasticity 2026 Kang et al

[Andy]

Abstract​

Cognitive dysfunction is a common and disabling clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), often described by patients as “brain fog.” These symptoms typically manifest as difficulties in attention, memory, and concentration. Chronic stress has been proposed as an important contributing factor in ME/CFS.

The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response, and prolonged adverse stress may contribute to HPA axis dysregulation, including altered cortisol rhythmicity and impaired negative feedback regulation. Such dysregulation may be associated with cognitive dysfunction in ME/CFS through mechanisms involving neuroinflammatory responses, oxidative stress, and disturbances in neurotransmitter homeostasis. Studies suggest that these alterations may affect hippocampal structure and function, thereby contributing to impaired learning and memory processes. As a key brain region involved in cognition and stress regulation, the hippocampus may be implicated in the neurobiological mechanisms underlying cognitive dysfunction in ME/CFS.

This review integrates current evidence on the potential role of HPA axis dysregulation and related neurobiological alterations in chronic stress-associated cognitive dysfunction in ME/CFS, with the aim of providing a theoretical basis for identifying potential intervention targets and informing strategies centered on HPA axis regulation.

Open access

 

[Trish]

Chinese research. I wonder whether people suffering from stress/burnout are being misdiagnosed as ME/CFS.

 

[Peter T]

Chinese research. I wonder whether people suffering from stress/burnout are being misdiagnosed as ME/CFS.

I have wondered this too in relation to the Chinese studies using students.

 

[Utsikt]

The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response, and prolonged adverse stress may contribute to HPA axis dysregulation, including altered cortisol rhythmicity and impaired negative feedback regulation.

To bad Wyller found no association between stress measured by hair cortisol and developing chronic fatigue following EBV..

 

[Creekside]

I've been living a pretty low-stress lifestyle since developing ME, and that hasn't had a noticeable effect on my ME, so I'm not in support of the theory. I expect that stress can be a factor in ME severity for some people, but that's just one of many factors that can influence severity without being an essential part of the ME mechanism.

 

[rvallee]

There is no plausible way to differentiate unrelated "chronic stress" from the consequences of this illness, so this will always be useless. It's complete nonsense to pretend this is even possible.

 

[Trish]

There is no plausible way to differentiate unrelated "chronic stress" from the consequences of this illness, so this will always be useless. It's complete nonsense to pretend this is even possible.

I don't understand what you mean. Are you suggesting chronic stress causes PEM?

 

[Axel]

I think we would have epidemiological data from all areas of war and repeated disasters, as well as from places of imprisonment, refugees camps, torture.
In culture, there ought to be numerous accounts of ME/CFS directly linked to clearly visible stress. Films, books, etc. Why would victims of stress or their witnesses go to great lengths to describe psychological rather than physical trauma, and never mention PEM? In fact, this condition would be extremely well known if it were linked to repeated and intense stress.

In reality, accounts of symptoms similar to those of ME/CFS are very rare in cultural works that deal with prolonged suffering.

 

[rvallee]

I don't understand what you mean. Are you suggesting chronic stress causes PEM?

No, they're saying they're assessing stress but most of the questions relating to stress would have answers that overlap with the consequences of living with a chronic illness. Same as a financial assessment might conclude that we have terrible financial skills, if it doesn't take into account that living with a chronic illness automatically causes financial strain.

 

[MrMagoo]

I think we would have epidemiological data from all areas of war and repeated disasters, as well as from places of imprisonment, refugees camps, torture.
In culture, there ought to be numerous accounts of ME/CFS directly linked to clearly visible stress. Films, books, etc. Why would victims of stress or their witnesses go to great lengths to describe psychological rather than physical trauma, and never mention PEM? In fact, this condition would be extremely well known if it were linked to repeated and intense stress.

In reality, accounts of symptoms similar to those of ME/CFS are very rare in cultural works that deal with prolonged suffering.

ah yes, it does rather fall apart when you look at it like that.

The thing is that it’s our fault for not being able to deal with stress, you see. All the war survivors, kidnapping victims, gang members etc are able to deal with stress the right way. We don’t. It may be because we are “type A” personalities who want everything our own way on our terms, or because we are depressives, avoidant of real life.
It’s very much a personality defect in certain individuals who need to just shake it off, go for a walk and quit malingering. I expect.

 

[Axel]

@MrMagoo, this is a subject that interests me. I hope to be able to compile and share descriptions of symptoms of illnesses or extreme conditions found in the literature that struck me as similar to my own experience.

As for survivors’ accounts, I have found similarities only in Varlan Shalamov, who speaks of an inability to recover following his (long) stay in the gulag. But Shalamov seems to have been unable to tolerate exertion before the moment he arrived, which is interesting. Solzhenitsyn mentions the case of prisoners who survive by lying down all day. They are no longer fed. They survive on peelings. This surprises everyone, but those who work and eat die one after the other, and those who go out of their way to get a double ration die first. It is very disturbing. It is a direct observation that physical exercise is harmful once a certain threshold of balance has been breached.

 

[MrMagoo]

@MrMagoo, this is a subject that interests me. I hope to be able to compile and share descriptions of symptoms of illnesses or extreme conditions found in the literature that struck me as similar to my own experience.

As for survivors’ accounts, I have found similarities only in Varlan Shalamov, who speaks of an inability to recover following his (long) stay in the gulag. But Shalamov seems to have been unable to tolerate exertion before the moment he arrived, which is interesting. Solzhenitsyn mentions the case of prisoners who survive by lying down all day. They are no longer fed. They survive on peelings. This surprises everyone, but those who work and eat die one after the other, and those who go out of their way to get a double ration die first. It is very disturbing. It is a direct observation that physical exercise is harmful once a certain threshold of balance has been breached.

I imagine there are survivors who have similar experiences to us, or not. Just like the general population.