Autistics vs. Socipaths

I want to make a bold proposition: the polar opposite of the autistic is the sociopath.

The autistic is internally chaotic and thus attempts to order the world–we seek order and seek to create order. That’s why young autistics in particular love to line things up (or make lists, as I did, which is really the same thing). It’s why we love structure in our lives and prefer for things to be predictable. Chaos added to chaos is just too much.

The sociopath is internally overly-ordered and thus attempts to bring chaos to the world–they seek chaos and seek to create chaos. They are extreme risk-takers and thrill-seekers. In its healthiest forms, they may climb mountains; in its unhealthiest forms, they may be serial killers. (Of course, not all thrill-seekers are sociopaths, though we do know that thrill-seekers do need more stimulation than does the average person.)

Each is seeking to balance order and disorder, as all of nature, from the level of quantum physics up through living things, human psychology, and human societies, does. When the internal world isn’t both ordered and disordered simultaneously, but is imbalanced in one direction or the other, balance in the external world is sought.

We do not have the sociopathic equivalent of the severe autistic because while too much chaos can make one unresponsive, too much order won’t have the same effect.

If my thesis is true, the sociopathic brain should be dominated by negative feedback (too much glutamine, too few synapses, etc.) and thus need stimulation (challenges). Challenges require strategies, so we should expect sociopathic people to be more strategic. We would also expect them to be more “social” and more outgoing and charming as a result. As a result, sociopaths both tend to be attracted to positions of power, and people tend to reward them by giving them power. You will find an extremely high percentage of politicians and CEOs to be sociopaths (though sociopathic CEOs also tend to be the least effective because of their tendency to take risks and not actually care about anyone else).

The autistic brain seems to be dominated by positive feedback (too much glutamate, too many synapses, etc.) and thus need a more calming atmosphere (which is why challenges can frustrate autistics). Autistics don’t seem to be particularly good at strategy, but tend to be creative problem solvers (mostly to try to order everything). They would then also be more likely to be introverts and anti-social, though this primarily comes about because we’re perceived as “socially awkward” by neurotypicals.

 

KLE1738, GABA, and a Possible Autism Connection

I have written on the role of GABA in autism here and here and here. GABA is involved in calming neural activity, and having less of it is associated with autism. Now we have discovered a gut bacterium that seems to survive only on GABA.

Many of us on the spectrum also have gut problems. It may be that we need these bacteria, named KLE1738, but it also may be that one can have too many. Or, seemingly oddly, not enough.

It may very well be that one needs these bacteria to clear out GABA. Without enough KLE1738 to eat excess GABA, it’s likely that GABA would get converted back to glutamate (enzymes work both ways, after all). This would keep glutamate levels high, and glutamate both contributes to positive feedback in the brain and to leaky gut.

This may in fact  be the more likely scenario simply because too many KLE1738 would result in starvation and result in the numbers dwindling back to normal. At the same time, one could imagine a scenario where there is a boom-bust cycle of KLE1738, with an alternation between too many and too few. Both too many and two few would result in GABA imbalances. And these swings could also result in the seeming bipolar behaviors we see in many on the spectrum.

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.

GABA Receptor and Synaptic Pruning

Recent research suggests a role for GABA receptor in synaptic pruning. Autism (and schizophrenia) are often associated with a lack of synaptic pruning, meaning neurons are more active, with positive feedback dominating.

GABA is associated with negative feedback, meaning the brain slows down to a steady-state. Glutamine is similarly associated with negative feedback. Glutamate is associated with positive feedback. All of these are neurotransmitters. More, they are closely related to each other, and can be biochemically derived from each other.

This suggests a few potential pathways to autism. If there is a problem with the GABA receptor, you would not get enough pruning. But if there is not enough GABA being produced, you would have the same effect. A mutation on either the GABA receptor protein or on one of the enzymes associated with GABA production could have pretty much the same result.

Neurons with unpruned dendritic spines get more input than do those properly pruned. The more input a neuron (or other complex system) has, the more is acts as though there is positive feedback. Indeed, it can result in increasing cycles, driving more input. In essence the brain becomes more hyperactive, at least until a physical limit is reached, at which point the system crashes, cycling down.

The result is a more active brain that may have some difficulty learning new things, but which may at the same time show exceptional abilities because of the higher activity. While the senses themselves won’t show increased activity at the source, you would see increased activity in the brain, resulting in the sensory overload associated with autism. One would even expect a certain degree of “phantom” sensory information–as we see with schizophrenia. Indeed, this association between autism and schizophrenia (which I keep coming across in different ways) does suggest that the old categorization of autism with schizophrenia meant that the researchers at the time were on to something.

Also, unpruned dendritic spines is a feature of a child’s brain before they turn two (more or less). The fewer pruned dendritic spines (and less cell death of neurons, which also occurs around the age of two, in conjunction with the pruned dendritic spines) there is, the more an autistic person will act like they are two years old, perhaps even younger. This can explain the neotenous features of autism, even among those of us who are considered to be only moderately autistic. And if the brain is kept in a pre-verbal state by being kept in an even younger state than that of a two-year-old, it can go a long way to helping us understand why there are nonverbal autistics.

A Report on an Experiment with Glutamine

After writing about the connection of glutamine to both leaky gut and autism, I decided to experiment upon myself and start taking glutamine supplements. I have been taking them since shortly after I posted that article, and when I was taking them more regularly, I must say that psychologically I did feel a bit different. By definition I could not tell you what feeling neurotypical feels like, so I can’t say I feel that way, but I did feel a bit calmer, more relaxed.

Now, as for the gut issues, after testing the effects of the glutamine one week:

Wednesday I had one cinnamon roll. No gut problems. Thursday, I tried two cinnamon rolls. Again, no gut problems. When I told my wife, she suggested we go eat at CiCi’s Pizza.

Now, the last time I had eaten at CiCi’s, I had a horrendous reaction. I had gut problems for three days. Acid reflux, the whole works. It was one of the worst reactions I’d ever had against gluten. But after taking glutamine for two weeks, I did not have near the reaction. I felt uncomfortable, with a little gas, but it was not a full-blown allergic reaction.

What glutamine does is reduce the diameter of the pores in the small intestines. Leaky gut occurs when the pores in the intestines open up too wide, allowing things like whole proteins through. This can trigger an allergic reaction. But glutamine causes the pores to tighten up. Food then has to be broken down more before it can cross over into the bloodstream. Gluten broken down into its constituent amino acids is no different from any other protein, so if you can prevent it from crossing over as a whole protein, you can eliminate the immunological response to it.

I have continued taking glutamine, for several years now. I mostly try to avoid eating anything with gluten in it, of course, but because I can now take a few gluten tablets before I know I’ll eat wheat, it’s nice to know I don’t have to continue obsessively avoiding it as I once had to do.

Tummy Trouble–Autism and the Gut

I read an article once that said Celiac disease is in part caused by having a leaky gut. Because I have an allergic reaction to gluten, but not full-blown Celiac disease (perhaps), I decided to look up what causes leaky gut and how to take care of the problem.

The problem: the pores are too wide.

The solution: probiotics and glutamine.

Glutamine is an amino acid related to the amino acid glutamate. For you chemistry types, the difference between the two is on the R-group. The OH on the glutamate is replaced by an amine — NH2. Glutamate is made from glutamine, and vice versa. However, it is possible for there to be a mutation on a gene that would result in an enzyme that prefers one over the other.

In some people with autism, there is very high glutamate in the brain. In fact, glutamate is an excitatory neurotransmitter, which implicates it in IWT autism. As it turns out, such autistics not only have high glutamate, but low glutamine as well. If the body is preferentially making glutamate over glutamine, this could not only cause autistic behaviors, but leaky gut and potentially gluten allergy as well. And perhaps not just gluten allergy, since leaky gut can result in a variety of food allergies.

This glutamate-glutamine connection to autism explains why so many on the spectrum have gut problems.

The above linked article also notes that “levels of GAD 65 kDa and GAD 67 kDa proteins, both of which are involved in converting glutamate to GABA, are reduced in the brains of individuals with autism, resulting in increased levels of glutamate in the brain substrate.” Why is this important? Low GABA levels increase feelings of anxiety. Social anxiety is, of course, a main feature of autism.

Thus, a system that preferentially makes glutamate over both GABA and glutamine would, it seems, result in someone having autism. Also, it seems that eating things that could provide GABA and glutamine might reduce some of the negative behaviors associated with autism. Indeed, there does seem to be some research which suggests glutamine supplements could help.

In fact, my son and I now take glutamine if 1) our stomachs are upset and/or 2) if we anticipate eating wheat. And it works. Without it, my son will throw up when he eats wheat, but with it, he won’t even complain about his stomach hurting. Now, in case you’re wondering if there’s a placebo effect, once my son was complaining about his stomach being upset. I couldn’t find any glutamine, but found something else and told him it was glutamine. He threw up anyway. Every other time he had complained about his stomach hurting and I gave him actual glutamine, he was fine.