Please consider that elevated glutamate will always reflect in elevated GABA eventually because glutamate is converted to GABA by glutamate decarboxylase. Only the short-term peaks, which can be triggered by exertion, would cause a dysbalance in the glutamate-GABA system.
Yes, good to bring up this interesting enzyme
glutamate decarboxylase (also called glutamic acid decarboxylase), which is involved in the glutamate dynamics of the brain.
This enzyme is not the only process responsible for clearing glutamate, though, because the brain also has
glutamate transporters to remove excess glutamate from the extracellular spaces of the brain.
I experimented with taking certain drugs (like ampicillin) to
increase the number of glutamate transporters in my brain, and I did notice a calmer, less wired and less anxious mind as a result — see
this post for details. A list of glutamate transporter boosters is given
here. Riluzole is the drug used clinically to boost glutamate transporters in the disease amyotrophic lateral sclerosis.
Researchers are looking into boosting glutamate transporter expression with drugs in order to help treat neurodegenerative diseases like Parkinson's, Alzheimer's, multiple sclerosis, epilepsy, etc.
But regarding glutamate decarboxylase and glutamate:
A while back I found
an interesting paper which mentions the possibility
coxsackievirus B4 and other Coxsackie B viruses might induce
autoantibodies that disable glutamate decarboxylase (more specifically, the GAD65 form of this enzyme).
This autoimmune attack may arise because of molecular mimicry between the 2C protein of CVB4 and glutamate decarboxylase.
If glutamate decarboxylase were to be disabled by such autoimmune attack, you would expect higher levels of glutamate in the brain, and you might expect some people to feel anxiety, since high glutamate in brain areas like the amygdala have been linked to anxiety in animal studies.
When I first caught the coxsackievirus B4 which later caused my ME/CFS, I soon developed moderate-to-severe
generalized anxiety disorder, as well as other mental symptoms, and it was clear that the physical effects of this virus on my brain was responsible.
And a few friends who caught the same Coxsackie virus from me also developed pretty severe anxiety. One person for example was hit with anxiety so bad that she locked herself in her apartment for 6 months, and never saw a single person, except for her daughter, because of the intensity of anxiety.
Because of my experience with CVB4 triggering major anxiety in several people, I became interested in speculative theories of why this virus might trigger anxiety.
I think virally-triggered microglial activation and the glutamate it releases could be part of the picture. And possibly a virally-triggered autoimmune attack on glutamate decarboxylase might also play a role.
If coxsackievirus B can trigger autoantibodies which disable glutamate decarboxylase, then this could help explain the "wired" symptoms of ME/CFS, the anxiety disorder which is sometimes present in ME/CFS, and the
central sensitization (CS) symptoms found in ME/CFS (like amplification of pain by central nervous system), since CS is linked to glutamate.
There are quite a few diseases which have glutamate decarboxylase autoantibodies, including type 1 diabetes (which is linked to coxsackievirus B4).
