Disclaimer

This TL;DR version is meant to be simplified and does not express the entirety of the science. If you want that, read the actual review article.

All sources will be listed under the source page and will be cited passage by passage in the actual review article.

This TL;DR version is by no means intended to be used as a professional reference and should not be taken as such. Again, read the actual review.

The Basis

GABA is a neurotransmitter involved in reducing excitability of the nervous system in GABAergic systems of the brain by changing the charge of the neuron involved in stimulation from positive to negative. GABA basically allows negatively charged chloride ions into the neuron, neutralizing the positive charge. When a neuron is positively charged, it's more excitable. When it's negatively charged, it's less excitable.

People diagnosed with Autism Spectrum Disorder, schizophrenia, epilepsy and a few other disorders, generally have some sort of GABAergic system dysfunction. 

Studies have shown that ASD diagnosed individuals commonly tend to have low levels of GABA.

Why is that?

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First, we need to understand epigenetics:

1) Epigenetics is the study of changes in gene expression or control, without alteration to the DNA sequence itself, unlike a mutation.

2) There's this thing called a methylation, which basically prevents specific portions of DNA from being read, which in turn helps to regulate which amino acids are used for each protein being expressed.

3) If the incorrect amino acid is used in the synthesis of a protein due to an incorrect sequence, whether that be from methylation pattern changes or mutation (not epigenetic), the protein can become dysfunctional and deformed.

4) Sometimes, things in the environment can change methylation patterns or effect "epigenetic marks".

Second, we need to understand what glutamate is:

1) Glutamate is an excitatory neurotransmitter, meaning it makes the charge of the neuron positive by allowing positively charged ions into the neuron.

2) Remember, positively charged neurons mean extra stimulation. In the case of autism, this could mean overstimulation.

Third, we need to understand how GABA is made:

1) There's an enzyme called Glutamate Decarboxylase (GAD67)

2) Glutamate Decarboxylase converts glutamate, the excitatory, into GABA, the inhibitory, with the use of vitamin B6 (pyridoxine), when there is too much glutamate in the system.

3) Glutamate Decarboxylase (GAD67) comes from a gene sequence called GAD1.

Fourth, we need to understand what screws up the production of GAD67:

1) Studies have shown that in utero exposure to LPS endotoxin, found in the cell membrane of gram negative bacteria causes decreased GAD67 in the hippocampus.

2) Examples of gram negative bacteria are: E. coli, salmonella, etc.

3) LPS endotoxin has been shown to screw up methylation patterns in the gene sequences of other types of cells.

4) LPS endotoxin causes an inflammatory immune response, which causes cells to make an enzyme (DNA Methyltransferase), which moves around methylations.

WE HYPOTHESIZE THAT LPS ENDOTOXIN EXPOSURE IN UTERO IS THE SPECIFIC CAUSE OF THE ALTERED METHYLATION PATTERNS ON THE GAD1 GENE IN ASD DIAGNOSED INDIVIDUALS, DUE TO THE PRODUCTION OF DNMT1 AS AN IMMUNE RESPONSE, AND IN TURN IS THE CAUSE OF THE E/I BALANCE OF GLUTAMATE TO GABA IN THE BRAINS OF ASD INDIVIDUALS. THIS CASCADE OF EVENTS CAUSES THE HYPER/HYPOSENSITIVITY TO STIMULI IN INDIVIDUALS DIAGNOSED WITH AUTISM SPECTRUM DISORDER.

Now that you have a basic understanding of how this works:

Thanks for your time.

with love,

The Spinach Causes Autism Team.