What can the science on the impact of acute infections on cognition tell us about ME/CFS?

[Hutan]

I have mentioned elsewhere that I describe PEM as being like having the flu, or another significant infection. I think there are studies that show that cognition is negatively affected during an acute infection, and I don't think it is just the distraction of pain. And I think there are studies that are beginning to throw some light on why that is, I guess how 'sickness behaviour' is generated.

I'm wondering if the cognitive effects of an acute infection are the same as those we experience in PEM, and if the biology driving those cognitive impairments and sickness behaviour in general can help us understand what is happening in ME/CFS.

 

[duncan]

I'm wondering if the cognitive effects of an acute infection are the same as those we experience in PEM, and if the biology driving those cognitive impairments and sickness behaviour in general can help us understand what is happening in ME/CFS.

Sure. albeit I wouldn't subscribe to the sickness behaviour thing. It's a non-human model.

But back to your initial observation, why wouldn't a chronic infection resemble what you position as an acute? Acute is merely less than 30 days, more or less. As a general rule of thumb.

We could all have, on paper, infections that : a} are discrete, b) infect different parts of our brains or other tissue, or C: a combination. These could all trigger ME/CFS - whether that is an aberrant immune response or signalling issue or whatever.

That being said, nothing I've experienced in 70 years of infections did to my brain what ME/CFS did - without bringing PEM into the conversation. Dead stop.

Or, of course, as you suggest, it's merely similarities between overt acute infection and PEM, but that seems more like asking if there are crossovers between acute infections and ME/CFS - PEM not withstanding.

 

[jnmaciuch]

I think I’ve mentioned this paper in a thread at some point but haven’t made a dedicated thread for it:

Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment​

 

[Hutan]

An interesting paper:

Infections can affect cognition:

In addition, a substantial number of articles have been published indicating that the immune system, in turn, can affect psychological and cognitive function (Allison and Ditor, 2014). However, the underlying signaling pathways and cell types involved are less well known. The observation that common symptoms of viral infections frequently include mood changes such as depressive-like behavior, cognitive deficits, somnolence, headache, and general feeling of malaise (Cunningham et al., 2007) may provide an entrée into studying this link between the immune system and behavior. Viruses that are known to induce behavioral changes (or “viral sickness behavior”) as part of the acute phase response include single-stranded (ss)RNA viruses such as influenza or double-stranded (ds)RNA enteroviruses (Dantzer, 2001).

As per the title, the paper is focussed on viral infections. I wonder - can all infections potentially cause sickness behaviour? Are the infections associated with ME/CFS are the same ones that are good at causing sickness behaviour? And there are some infections that cause sickness behaviour but don't seem to trigger ME/CFS, and, if so, is there something different about that sickness behaviour?

A theory of ME/CFS etiology ideally needs to take into account the fact that some bacterial infections seem to cause ME/CFS e.g. Q fever.

The paper also mentions interferon treatments are known to cause side effects that are similar to sickness behaviour, and proposes a mechanism for the production of cognitive dysfunction.

In this study, we found that in vivo synthetic dsRNAs, a prototype RNA virus, and recombinant type I IFN, all shared the ability to induce cognitive impairment and mood changes. Peripheral IFN-β activated interferon receptor chain 1 (IFNAR) expressed on brain endothelia and epithelia, which released the cytokine CXCL10 into the brain parenchyma where neuronal function was compromised.

 

[jnmaciuch]

As per the title, the paper is focussed on viral infections. I wonder - can all infections potentially cause sickness behaviour? Are the infections associated with ME/CFS are the same ones that are good at causing sickness behaviour? And there are some infections that cause sickness behaviour but don't seem to trigger ME/CFS, and, if so, is there something different about that sickness behaviour?

Interferon can definitely be stimulated by multiple types of pathogens—TLR4 recognition induces a pretty strong interferon response and it recognizes components of bacterial cell walls. though some antigens might have different affinities for these and other receptors which changes the strength or ratio of downstream signaling molecules.

 

[Hutan]

That's the proposed mechanism from the paper. VSV-M2 is an example of a virus causing a peripheral infection.

We found that the splenic MAVS pathway and its activation by RNA ligands with subsequent stimulation of RIG-I and MDA5 as equivalent to VSV-M2 infection were important for sickness behavior. The presence of IFNs in the circulation stimulated IFNAR1-dependent production of chemokines by brain endothelial and epithelial cells. These chemokines could then mediate fundamental changes in synaptic network function and coupled cognitive functions by engagement of neuronal CXCR3.

Should we make a thread for the paper @jnmaciuch or has it been discussed in detail already?

 

[jnmaciuch]

View attachment 28932

That's the proposed mechanism from the paper. VSV-M2 is an example of a virus causing a peripheral infection.


Should we make a thread for the paper @jnmaciuch or has it been discussed in detail already?

I think I may have just dropped the link somewhere else but the discussion moved past it quickly. Would probably be worthwhile to do separate thread—I just didn’t have a free moment on my laptop at the time

 

[Hutan]

I've made a thread for the paper here - link.

 

[Peter T]

Even though it was some thirty years ago, I do clearly remember trying to ring the on call doctor service in the middle of the night in the first twenty four hours of my ME triggering acute episode of glandular fever (mono). Just dialing the phone number was a struggle (my digit span was down to one so it took several attempts of dialing the number one digit at a time to get through) and recalling my name and date of birth felt as though it took hours.

Though this was an extreme it does not feel qualitatively different to my ongoing experience of brain fog in more severe PEM. Certainly a reduced digit span is characteristic as is time taken to retrieve even well known or even over learned information.

(Digit span, with the norm being seven (plus or minus two digits) recalled in immediate memory, has since been linked to the severity of my concurrent ME/health. Premorbidly my span was eight or nine numbers, during the worst of PEM it can go as low as one digit, at present, a relatively good day, it is perhaps five or six.)