I think we should be a bit critical of Dr. Younger as I don't think his hypotheses are well thought out and as others have said I think he is suffering a bit from "not invented here" syndrome, especially since he's built his entire lab to focus on studying these hypotheses and not for example autoimmunity or infectious causes.
You might equally find that labs or researchers studying autoimmunity only focus on that area; but that itself is not any reason to criticize the autoimmune hypothesis of ME/CFS. Science by its nature if often divided into specialties.
There are so many diseases that cause neuroinflammation as part of the disease process but it certainly isn't the root cause and they aren't treated as such. Most if not all autoimmune diseases cause neuroinflammation as a side effect and we've discussed this countless times on PR.
In the case of diseases with significant mental or cognitive symptoms such ME/CFS, depression, schizophrenia or bipolar, I believe their association with neuroinflammation is a relatively recent one, so the fact that these diseases are not treated by anti-inflammatory protocols may just be because this knowledge is so new.
So many of us have taken combinations of drugs and supplements that are known to potently inhibit microglial activation etc. but they just don't work in a big enough way to be considered treatment. If ME/CFS was a putative neuroinflammatory disease then many of us would be gone into remission or significant recovery by now
You may be taking microglial activation inhibitors, but unfortunately I don't think there is any evidence in any given patient that these drugs or supplements are indeed inhibiting microglia.
Even if they were, is inhibiting microglia the right approach to tackling brain inflammation? There are many things going on within brain inflammation, including changes to astrocyte function. Some researchers speculate it is extracellular glutamate build-up from brain inflammation that is the problem, and this involves microglia which release glutamate as well as astrocytes which help clear it.
Some ME/CFS patients experienced dramatic reductions in symptoms when taking a drug which increased glutamate clearance from the brain (see
this thread).
I myself had a lot of success in eliminating my severe generalized anxiety disorder using supplements that targeted brain inflammation (see
this thread). And when I began regularly taking these supplements, I noticed my ME/CFS symptom slowly but significantly improved, as this may have been a result of their anti-neuroinflammation effect.
Note also it is not just microglial activation that is the issue, it is what
phenotype microglia become activated into that counts. There are two main types of microglial activation:
Classical microglial activation which is neurodestructive (and involves COX-2, iNOS, IL-6, and TNF-alpha).
Alternative microglial activation which is neuroprotective (and involves FIZZ-1, YM-1, Arginase-1, and IL-4).
Classical microglial activation is the "kill" mode which destroys pathogens in the brain; alternative microglial activation is the repair mode which heals the brain. When we talk about "microglial activation" and is destructive effects, we are tacitly referring to classical microglial activation.
It may be that what we need to do in ME/CFS is not stop microglial activation, but rather change the phenotype of microglial activation from the neurodestructive classical activation phenotype, to the healing and neuroprotective alternative activation phenotype. Supplements that can do this are given at the bottom of
this long post.