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.