I have recently written about the complexities of the underlying genetics of autism, including issues of gene regulation. That particular article focused on RNA regulation through methylation. Now there is more evidence for the importance of RNA regulation in Nature. The CPEB-4 protein is involved in the addition of the poly-A tail to mRNAs, and there is a version that specifically regulates this in genes connected to autism.
Each mRNA–which allows the genes for proteins to be turned into those proteins–has a tail of adenosines (one of the nucleotides) added to it after it is transcribed from the DNA. This is important because when the mRNA is translated into a protein, a nucleotide is removed from the end of the RNA. The longer the tail, the more proteins can be made. If only short tails can be produced, there will not be enough proteins produced. CPEB-4 seems to be involved in regulating the length of the poly-A tail.
As already mentioned, things in the cell are complex. In learning more about this gene, I have learned that the protein, cytoplasmic polyadenylation element binding protein, is found in the dendrites and cell body of neurons, but that “treatment of neurons with ionotropic glutamate receptor agonists causes CPEB4 to accumulate in the nucleus. ” Here we again see a gene/protein related to autism connected to glutamate. Stress conditions in the brain–low oxygen or glucose, for example–cause CPEB4 to be sent from the cytoplasm to the nucleus, where they cannot do their job of regulating poly-A in the cytoplasm.
As noted, the CPEB4 gene seems to be central, but that doesn’t mean we should necessarily see mutations in it connected to autism. There could be mutations in the gene(s) for the ionotropic glutamate receptor, or in the gene(s) for glutamate production, or in some other regulator of CPEB4. So while you are bound to find popular articles out there crowing about the fact that there is a “central gene” connected to autism, don’t be mistaken: it’s still a complex situation.
This past week I have had trainings for my work. I have been hired as a paraprofessional in a middle school behavioral unit in Plano ISD, and that means I had to go through four days of training. I have been utterly exhausted for four days.
I have had to be in a room with about 30 strangers for four days. On day one, I’m not sure I could have stimmed more or faster. My legs shook and I was fiddling around with my pen. I stimmed less each day, but I didn’t seem to get any less exhausted. I fortunately didn’t have training today, so I was able to sleep in (not to mention going to be a little early)—I got 10 hours of sleep (I usually wake up naturally right before I get 8 unless I’m that exhausted).
My wife noted that I seem to get exhausted that way if I have a day full of meetings. I also get this way the first week or two of a new job. One can only imagine what impression that makes. After that first week or so, though, my brain adjusts to the new situation, and I am back to my old normal self and degree of energy.
Given that this is what a new situation does to me, one can also perhaps imagine why I may not want to participate in these kinds of meetings or trainings, why I may not want to start a new job or switch jobs, or why I may want to avoid situations in where there will be a large number of people I don’t know and with whom I have to interact. I can only imagine what I must look like to others.
Coincidentally, having this level of self-awareness only makes things worse in these situations, because it only makes me more anxious, which only makes me stim more and harder. It’s a positive feedback nightmare. And when your brain is running at full blast for hours on end, it’s exhausting.
There is a gene–NOTCH2NL–that is found only in humans (and Denisovans and Neanderthals, once upon a time). It’s actually part of an ancient family of genes, but this particular version is only found in humans–and, more, we have multiple copies of it.
What this gene does is slow down the development of stem cells into neurons. Why does this matter? This delay actually causes more stem cells to turn into neurons, meaning without NOTCH2NL, our brains wouldn’t have anywhere near as many neurons and thus wouldn’t be anywhere near as big.
This gene is found on chromosome 1, in the location 1q21.1. As the original article in Cell notes, additional copies of this region have been found in people with autism. In other words, it’s possible that at least some autistics have even more copies of NOTCH2NL, resulting in even more neurogenesis. More neurons could push the brain toward greater positive feedback, which seems to be a main feature of autism regardless of various potential causes.
What this implies is that the very process that made us humans–the proliferation of NOTCH2NL (after it evolved)–could be behind the emergence of autism. In other words, some autistics may be more human than human.
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.
If you are anywhere at all on the autism spectrum, you have anxiety. It seems to come with the territory. It’s easy to find things about which to be anxious, but in truth the feeling seems to just be there, as background noise, never ceasing.
At the same time, there are plenty of things that give us anxiety. Facing new social situations is an obvious one. While we may be standing off to the side, sitting there quietly, seeming to only be listening, perhaps appearing aloof or even arrogant, the fact of the matter is that the situation makes us anxious, and it may take us a while to get used enough to the situation to come out of our shells. That probably won’t happen at the end of a party, but it might happen at the end of a week-long academic conference.
One thing that causes us anxiety is not working on our project, whatever that project may be. Most of the time, we are our work, and that means when we are working on a project, we almost don’t know what to do with ourselves when we are not working on it. When I am working on a project–whether it’s a novel, a poem, a play, a paper, a nonfiction book, or some other project–I am always thinking about that project. I am anxious when I am not working on my project. When I am working on it, I am anxious to finish it. It drives me, but it also drives me a little crazy. I seem to be absent-minded, but I’m always thinking about my project. It never ends, until the project is over.
And then I start on the next project, and the cycle of anxiety starts all over again.
Even now, as I am writing this, Daniel is full of anxiety because he has a project he wants to do, but he can’t get his younger brother to cooperate with him (or, more honestly, obey him and do everything he says–something that makes Dylan’s supreme independence a perfect foil for Daniel). Because he is anxious and frustrated, he yelled at his mom, which caused me to have to stop and make him apologize to her.
These frustrations/anxieties are part of our daily experience in dealing with other people and the the world in general that constantly imposes on us and prevents us from working on our projects, which is really all we want to do. Daniel is going to have to learn that you can do more with honey than vinegar, or he’s going to just stop trying to involve anyone and do work that doesn’t involve anyone else to get it one.
You know, like writing.
So there are certainly many things that make us feel anxious. The fact that we identify with our work, and not working on our work makes us feel anxious to work is part of it, but it’s hardly all. Sometimes, you just feel anxious. And it may not be caused by anything in particular. The fact is that most of the time, we simply feel anxious because we feel anxious. We can look for causes, but how often will that be simple justification of the feelings? The fact of the matter is, anxiety is co-morbid with autism. Sometimes it just is. It is the background noise of the world when you are autistic.
I’m currently reading the book Educating Children with Autism, which is a government report–and reads like one. Meaning, it’s one of the driest, most boring things I’ve ever read. It’s also not exactly chock-full of new information. I’ve run across most of what it has to say in various other places (and said better in those places). But that doesn’t mean there aren’t a few tidbits there.
One tidbit is the fact that “staring spells” are in fact small seizures (30). If you have autism or know of someone with autism, you know they can sometimes fall into “staring spells,” or “space out.”
Actually, that tidbit can also be found in Temple Grandin’s Thinking in Pictures (6).
A seizure is simply caused by an abnormal electrical discharge in the brain. Getting caught in a positive feedback loop, for example. These kinds of seizures are called “absence seizures” because there are only a few seconds of consciousness lost, with no other symptoms. Externally, it appears that the person is just staring blankly.
I have these seizures all the time. I’ve had them for as long as I can remember. I just didn’t know they were seizures until I read about them in the two books above and looked up what kinds of seizures they were. They’re not really a big deal, and often you don’t even know you have had one.
Of course, if you have one in front of a person, it’s bound to be noticed. I’ve been asked a few times whether or not I was okay. If I’m busy doing something and I have one, I’ve been asked if I’m thinking about something (I usually am, so I usually answer in the affirmative). Once, when I had one at a Starbucks I actually had someone rather aggressively ask me what I was staring at, and even after I told him I wasn’t staring at him at all, but was rather thinking about something (I now know better), he told me to stop it. I guess the good thing now is that I if something like that should happen again, I can tell the person I’m prone to absence seizures, and he can feel like the ass he is.
I also have a “twitch” that began as a “head turning” but now mostly manifests itself in a head-shaking. It happens mostly when I’m most relaxed. If I’m focused, I don’t have them. It turns out that those are another kind of seizure, a partial seizure known as a simple motor seizure.
Given that these minor seizures are a feature of autism, I now have an explanation for these experiences. Who would have guessed they were seizures?