One Gene to Regulate Them All (or, at least many of them)

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.

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RNA Methylation

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.

Autistic Masking

A recent trend I have seen on Twitter among autistics there involved opposition to “autistic masking.” Not all autistics can mask, but many if not most can. And that creates a number of problems for us.

I’m honestly a little torn on this issue, because on the one hand, I realize that literally everyone “masks”–you are a spouse, a parent, a friend, a child, an employee or employer, and there may be remarkably little overlap among those personas you present–and on the other hand, autistics both have to mask a lot more (like stimming), and masking is much more exhausting for us than it is for neurotypicals.

Over time, though, a lot of masking just becomes second nature. Sometimes you mask without even realizing it. For example, recently Daniel started engaging in palilalia. It was only recently that I realized palilalia was something I also did–only, I did it silently, in my head. I don’t see any particular benefit to my “unmasking” my palilalia. I’m still doing it–silently, in my head–and all it would do would be to cause unnecessary stress on others for me to do it out loud.

There are a lot of things people keep to themselves. People self-censor all the time. It’s called being polite. It’s called having good manners. You learn good manners. It’s not something anyone is born with. It’s a form of masking, and it’s a form of masking that makes you a better person over time.

However, the last century has seen a rise in what I would call the “cult of authenticity.” Everyone seems to think–or at least say they think–that people ought to be more “authentic,” that they need to be their “authentic selves.” I say that’s nonsense. I don’t want people to be their authentic selves. I want them to be better, nicer, kinder, more generous than their authentic selves–even if their authentic selves are good, nice, kind, and generous. The cult of authenticity has ruined art, poetry, relationships, and general civility. Rather than expecting everyone to rise up to greater heights, we want everyone to wallow in the shallows of their “authentic” selves.

At the same time, I can understand why many autistics are truly tired of masking. Masking is, for us, a great effort and, even when well-performed, prone to breaking down. Masking for neurotypicals is easy and relatively effortless. Masks can change in less than a moment. This is hardly the case for autistics. We have to always think about what it is that the person in front of us wants to see from us. And heaven help us if the situation changes and the mask has to change. Worse, we have to mask things that others don’t have to mask. Neurotypicals are sincerely interested in other people and stories about others people, while very often we autistics aren’t. But we know it’s important to others to talk about those thing, so we feign interest. Also, if we are allowing a lot of back-and-forth in conversation, you may rest assured that it’s only because we are artificially cutting ourselves off despite having so much more to say. This, too, is a form of masking.

I suppose the real problem with masking is that while presumably neurotypicals do get times when they can be their “authentic selves” around certain people, we too often feel like we can never be ourselves–even around friends and family. When can I stim without feeling self-conscious about it? (Of course, I also rarely stim when I’m fully comfortable, so I suppose wanting both is contradictory in nature, at least for me.) When can I just talk and talk and talk about what interests me? I pretty much never get that opportunity, and I find myself less and less able to have conversations about my interests that go on for as long as I want them to go on (ah, the beauty of grad school in allowing such conversations!).

I often put up with people touching my wrists (which makes me want to crawl out of my skin), and I have to wear suits and long-sleeve shirts (remember my wrists?) in certain situations. I’ve had to get over being interrupted when I work so that I’m not biting people’s heads off. Even then, I really haven’t “gotten over” the intense irritation I get at being interrupted when I’m working on something, especially my writing. Rather, I mask it, taking a moment to calmly move out of the zone and into a space where I can converse. But let me ask you: should I have just kept biting people’s heads off, or should I have masked that reaction? I think we should probably all agree on the answer to that.

Living in the world means masking. This is true for all people. However, it’s harder for us autistics. And we’re rarely if ever given the opportunity to truly be ourselves. Which only makes it harder. Which is no doubt why there is this movement against masking. We have been pressured into always-masking (and always doing so poorly), and many have gotten sick and tired of it. The answer, for them, is to demand from everyone that we be allowed to never mask anymore. I think there are rhetorical benefits to that approach insofar as it draws attention to what we have to do to get along (and even then, not enough)–especially if it can draw attention to the fact that masking, because it’s so hard for us, actually harms us not only through mental exhaustion, but from people reacting so poorly to when the mask starts to crack. We need people to realize what we’re doing and how it can harm us. But, truth be told, we’ll never be able to stop masking. It’s simply part of being human.

Autism and the Emergence of Art

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 and Autism II

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

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?

NYT Op-Ed Educates People on Autistics

The New York Times has a fantastic op-ed in which the authors argue that autistics  are really social, only we get our actions misinterpreted as being uninterested in being social. For example,

Take eye contact. Some autistic people say they find sustained eye contact uncomfortable or even painful. Others report that it’s hard to concentrate on what someone is saying while simultaneously looking at them. In other words, not looking someone in the eye may indicate that an autistic person is trying very hard to participate in the conversation at hand. Unfortunately, this attempt to engage often gets interpreted as a lack of interest.

I have certainly told people exactly this, that I can either look them in the eye or pay attention to what they’re saying, but I can’t do both. Of course, most people interpret lack of eye contact as a lack of interest in what you’re saying, but when it comes to autistics, it really means quite the opposite.

The rest of the piece is quite good, and I’m thrilled the New York Times ran it. It’s gratifying to be treated as a fellow human being for a change.