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.
People rarely understand just how complex molecular biology really is. People are out there looking for the “autism gene” or “genes,” but have only found a low percentage of people who can be connected to a specific genetic change in a particular protein-producing gene. For many people, that means that environment is likely to be the main cause. However, there are many other factors in molecular biology that will have an effect on cellular outcomes that won’t be connected to a mutation in a protein-producing gene.
There are a variety of other things active inside a cell that affect protein expression and function. DNA can be methylated such that certain genes are turned off. RNA can be methylated as well, which affects translation of mRNA into proteins. The benefits of methylating RNA over DNA is that the cell is able to respond to its environment much more quickly. As the linked article notes, this allows for proteins to be turned on at synapses very far from the neuron’s nucleus. Both forms of methylation are of course a result of a protein or protein complex, meaning there is a gene or set of genes involved in them as well. So it still ends up being genetic–the only thing is that we won’t be looking for direct proteins, but rather proteins involved in these regulatory processes.
Insofar as the numbers of certain proteins in synapses is connected to certain varieties of autism, one should definitely look at regulatory elements in the production of those proteins, the transport of those proteins, the folding of those proteins, and the insertion of those proteins into the membrane when relevant. Those will all involve completely different protein complexes and processes, meaning there are a large number of potential pathways to the same basic outcome.
I think it’s important to learn how the various forms of neurodiversity come about simply because I support any and all basic research. I do think, though, that we need to change people’s attitudes about autism in general as we make these discoveries. It may be–and it’s likely to be–the case that those with such severe autism that they are rendered severely disabled (autism 3) are genetically quite different from the rest (autism 1 and 2), and that there might be a very wide variety of things we’re placing under the “autism” umbrella.
At the same time, it’s clear that my autism 2 son inherited his autism from me, though I’m only autism 1. This suggests either an environmental factor also being in play, or combinations of genes , or both affecting degree. There may be gene combinations which result in autism, so that if for example, you have gene X and gene Y, and mutation x’ and mutation y’, then XY would be neurotypical, X’Y would be neurotypical, XY’ would be neurotypical, and X’Y’ would be autistic, for example. Or there could be certain benefits to X’Y or XY’ for those individuals, yet when they get together and make an X’Y’ autistic child. Or X’Y’ is more sensitive to environmental factors than are the other three combinations, such that in the right environment, even X’Y’ won’t result in autism.
As I said, these things are very complex. Anyone who tells you they have a simple answer to the cause of autism is selling snake oil.
Around 30,000 years ago, extremely detailed, realistic art emerged in cave paintings. Believe it or not, there are many scholars out there who believe this occurred because the artists were autistic.
Lead author of the paper, Professor Penny Spikins from the Department of Archaelogy at the University of York, said: “Detail focus is what determines whether you can draw realistically; you need it in order to be a talented realistic artist. This trait is found very commonly in people with autism and rarely occurs in people without it.”
Which itself raises some interesting issues regarding the history of art and the proliferation of realism during periods such as the Renaissance.
A related article also suggests that human societies really took off only after they learned to tolerate the presence of people who thought and behaved differently. Oddly, we seem to be losing that trait even as we are gaining acceptance of people who merely look differently.
Either way, it’s obvious that autism has been around for a very long time indeed. The idea that autism may be adaptive for humans at the level of group selection is something I myself have suggested. It would appear that autistics are important for the development of artistic styles and a concentration on extreme realism. Of course, that means that during artistic periods dominated by iconoclasm, such as we saw in Modernism and Postmodernism, select against autistic artists. It is likely, though, that we will again have our day.
Who is up for another autistic-lead renaissance?
Oxytocin is an important neurotransmitter, and one which has been implicated in autistic behaviors. Known as the “love hormone,” there’s a lot more to it than that. According to Psychology Today,
It regulates social interaction and sexual reproduction, playing a role in behaviors from maternal-infant bonding and milk release to empathy, generosity, and orgasm. When we hug or kiss a loved one, oxytocin levels increase; hence, oxytocin is often called “the love hormone.” In fact, the hormone plays a huge role in all pair bonding. The hormone is greatly stimulated during sex, birth, and breastfeeding. Oxytocin is the hormone that underlies trust. It is also an antidote to depressive feelings.
As I have noted before, oxytocin has a dark side, meaning low levels of oxytocin not only reduce one’s desires for social interaction, but also reduces the tendency to engage in “groupthink,” the worst versions of which are racism and sexism. To the extent that autistics don’t engage in in-group/out-group thinking, we have a general tendency to not engage in racism and sexism.
However, do note many of the behaviors noted above. I suspect that it’s not just any empathy that’s affected by lower levels of oxytocin, but the specific kind autistics have problems with. Coincidentally, the kind of empathy we autistics have problems with is the same empathy that actually makes people favor their in-groups over out-groups and thus can make people behave in racist and less moral ways.
Also note that oxytocin is as much the sex molecule as the love molecule. I have read that many autistics have little to no interest in sex. While that’s certainly not universal (I’m sure other hormones, etc. are involved and affect sex drive as well), it seems to be much more common among autistics than neurotypicals. Low levels of oxytocin would explain this phenomenon. Ironically, since having sex increases oxytocin levels, those who lack interest in sex due to low oxytocin levels are behaving in such a way as to maintain low oxytocin levels.
The connection to trust is a bit odd to me, as I find autistics to be generally quite trusting. However, it may make sense if trust is tied to in-group members, and distrust to out-group members. Without that distinction, it may be that we are simply more trusting of out-group members, and thus we seem more trusting overall.
Here is an interesting overview of the research to day on the connection between oxytocin and autism. I have also written about the connection between touch and increasing oxytocin levels in a post titled Hugs Help.
The mesolimbic reward pathway is a neural system that helps people be more social. The larger it is, the most social a person is. Perhaps not surprisingly, it’s smaller in people with autism.
What this pathway seems to do is make social interactions pleasurable. Again, the larger it is, the more pleasurable one’s social interactions are going to be. That is, you get rewarded for being social. While it’s likely social interactions aren’t actually made painful by having a smaller pathway, social interactions simply aren’t as pleasurable. If you’re not being rewarded for something, how likely are you to do it?
The authors point out that they haven’t untangled cause and effect quite yet on this. Do more social interactions cause the mesolimbic reward pathway to increase, or does its size increase social interactions?
This makes me wonder, though, why it is that many of us on the spectrum find pleasure in certain things–more so, it seems, than do others? For example, my clipboard gives me pleasure. I use it to do most of my writing. My books give me pleasure. I’m very happy just looking at them in my library. Is there a pathway in the brain for object-pleasure? Or does the mesolimbic reward pathway make social interactions so much more pleasurable that neuroptyicals prefer social interactions over the pleasure things give them?
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.