A Variety of Genetic Pathways to Intense World Autism

Recent research into the gender bias of autism (4:1 in favor of males), has shown there are sets of genes that are expressed more by males than females which express certain sets of autism genes. In this research it was found that

Many of the shared genes in these sets are related to microglia, immune cells in the brain that trim away excess neuronal connections, or synapses, in the developing brain and that may be dysfunctional in people with autism. One of the sets also contains genes related to star-shaped cells called astrocytes, which may be involved in learning and memory; these cells are thought to be both smaller and denser in autism brains than in controls.

Failure to trim away extra neurons is a recurring theme when it comes to autism.

If microglia cannot work properly, we would expect less synaptic trimming to take place. Which means a hyper-connected/hyper-active network.

Astrocytes are involved in clearing away neurotransmitters, and if they cannot work properly, we would expect buildup of certain neuotransmitters. Surely some of those neurotransmitters would be glutamate, which acts as a positive feedback neurotransmitter. Which means a hyper-active network.

Genes involved in the glutamate-glutamine-GABA cycle would contribute to imbalances in these neurotransmitters. Imbalances in favor of glutamate would result in a hyper-active network.

Genes involved in serotonin production can affect synaptic trimming, since serotonin is needed to trim synapses. Low serotonin would result in less trimming, meaning a hyper-connected/hyper-active network.

Vitamin D is involved in serotonin production, and vitamin D deficiency has been connected to autism:

vitamin D hormone activates the gene that makes the enzyme tryptophan hydroxylase 2 (TPH2), that converts the essential amino acid tryptophan, to serotonin in the brain. This suggests that adequate levels of vitamin D may be required to produce serotonin in the brain where it shapes the structure and wiring of the brain, acts as a neurotransmitter, and affects social behavior. They also found evidence that the gene that makes the enzyme tryptophan hydroxylase 1 (TPH1) is inhibited by vitamin D hormone, which subsequently halts the production of serotonin in the gut and other tissues, where when found in excess it promotes inflammation.

As noted before, vitamin D absorption is affected by glutamine/glutamate levels.

In other words, mutations affecting microglia, macroglia, glutamate-glutamine-GABA production, serotonin production, and vitamin D levels can all have pretty much the same effect in having hyper-connected/hyper-active neurons. Those are a large number of causes resulting in essentially the same effect.

The Complex Biochemistry of the Autism-GI Connection

From the “I’m not at all surprised at this,” section, researchers have found GI problems in autistic people to be genetically linked to their autism. Now, while I have connected autism to leaky gut through glutamine, these researchers have connected autism and the GI tract through serotonin.

Serotonin is derived from tryptophan, an amino acid, and serotonin, oxytocin, and vasopressin, three brain hormones that affect social behavior, are all activated by vitamin D hormone. There is recent research that shows a connection between this system and autism. It is perhaps not surprising that a system involving neurotransmitters plays a role in certain kinds of autism.

It turns out that low vitamin D affects the levels of these hormones. And, coincidentally, when I went to see the doctor a few years ago for a checkup, he told me I had low vitamin D.

Consider this fact from Mercola: “vitamin D is a fat-soluble vitamin, which means if you have a gastrointestinal condition that affects your ability to absorb fat, you may have lower absorption of fat-soluble vitamins like vitamin D as well. This includes gut conditions like Crohn’s, celiac and non-celiac gluten sensitivity, and inflammatory bowel disease.”

All of those gut conditions are caused by leaky gut. Leaky gut is caused by too much glutamate relative to glutamine. This in turn affects the ability to absorb vitamin D, which in turn affects the production of the above neurotransmitters. Including serotonin, which in turn affects the gut. 

I have vitamin D and glutamine tablets in my cupboard. It looks like I’ll be taking them every day from now on. And asking Daniel’s doctor about whether or not Daniel has a vitamin D deficiency. Because Daniel has severe GI problems.