A Time Window for Treating Autism?

One of the more popular theories explaining autism symptomology concerns an excitatory:inhibitory (E:I) imbalance in the brain [1, 2]. This states that an E:I imbalance leads to overexcitation in pyramidal neurons and thus the symptoms of autism. While E:I imbalance is potentially targetable via a number of interventions, such as GABA agonists, etc., the question remains: Is there a limited developmental window in which symptoms can be successfully reduced? With the paradigm in autism that “younger is usually better” that’s an important question to answer.

A new study suggests that, at least for certain causes of autism, treatment and rescue in adulthood is indeed possible. Using a mouse model to mimic CNTNAP2 mutations found in human cases, researchers at Stanford University have shown that not only do these mice exhibit behavioral and neurophysiological deficits akin to autism, if you use targeted treatment with optogenetics on the medial prefrontal cortex (mPFC) to specifically increase activity of inhibitory neurons and decrease that of excitatory neurons in that region, autism-like symptoms dramatically reduce.

fareler-ve-ozellikleri.jpg

While: 1) humans are not mice, 2) most people with autism don’t have CNTNAP2 mutations, and 3) using optogenetics is not a particularly viable treatment on humans– the series of experiments nevertheless show that it is theoretically possible to reduce autism symptoms even in a model that has structural brain malformations, which many scientists tend to assume are irreparable. It also lends support to the idea that the characteristic symptoms of autism in some cases may be functional in origin and therefore are potentially treatable, e.g., they are not the result of epileptic damage, etc. The problem then becomes identifying an individual’s specific physiological deficits and tailoring a treatment regime to him or her.

For instance, while Cntnap2 mutant mice in this study required treatments targeting both excitatory pyramidal neurons and inhibitory interneurons, another autism mouse model, Scn1a-deficient mice, can be easily rescued with typical GABA agonists, thereby targeting only interneurons directly.

To recap, this study is remarkable in a few ways:

  1. It shows that symptoms characteristic of autism can be rescued even in a brain that exhibits structural malformations.
  2. It reinforces the importance of the prefrontal cortex in autism, as targeting just the mPFC in these mice dramatically reduced symptoms in general. This is akin to my husband’s work using low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC).
  3. It suggests that although E:I imbalance may be an underlying cause in autism, its triggers can target different cell populations in different ways. While SCN1A mutations may largely impair the inhibitory cell population, CNTNAP2 mutations obviously impair both excitatory and inhibitory neurons, requiring treatments that target both those populations of cells. This realization may therefore lead to more refined approaches in personalized medicine.
  4. This study indicates that at least in some cases of autism, significant symptom reduction is theoretically possible well into adulthood, provided we are able to develop the means to target those cell populations successfully.

This last point will be the greatest challenge. But hopefully the move towards personalized and precision medicine will get us there.

 

7 responses to “A Time Window for Treating Autism?

  1. It really does depend on the cause of the autism,which is why I advocate for extensive medical testing of autistics,especially those with multiple comorbidities.There is a certain per centage of autism that is caused by underlying metabolic and immune disorders,or even a brain tumor.
    http://www.rsna.org/Autism_Research.aspx

    All of which can be treated.The only way to find out is tests,tests,and more tests.Metabolic and autoimmune disorders are treatable at any age.

    I say this as someone with a diagnosis of moderately severe autism,that was severe enough that I could not live independently,or perform many of the basic functions of day to day living.In my 40s,I was found to have a condition called cerebral folate deficiency.It took a few years,but treating this condition eventually reversed my autism.This is a condition that rarely occurs in a diagnostic vacuum.I also have been found to have a unique,and complex,chromosomal disorder.There are multiple other treatable metabolic causes of autism,such as tetrahydrobiopterin metabolism.

    Treating these disorders,or treating autism with any other science based method,gets us to the lies and fallacies of the neurodiversity movement,a subject near to both you and your husband.While neurodiversity advocates agree autism is a congenital condition,although they do not use that word,they claim is treatment of autism would destroy who you are as a person.Nothing could be further from the truth.

    • I have to admit I myself am on the cusp of the ND movement, as that is the realm from which I originally came. Not only was I a moderator on Wrong Planet for a number of years, but I also began and ran my own smaller autism forum. While I never adhered to the militant version of ND proposed by the folks at Aspies for Freedom and I was always supportive of science-based treatment interventions, I still appreciate the concept that ultimately Biology does not recognize the human paradigm of Pathology. In Biology, either something works under a particular circumstance or it doesn’t– and many biological processes occur on a spectrum of severity. Even cancer itself does not have as fine a delineation between “normal” and “pathological” as most people think. Benign tumors challenge that paradigm for instance. And people with high-functioning autism can likewise challenge the pathological paradigm. The main takeaway from ND that I like is to be cautious about pathologizing a person’s brain and behavior, because it’s fundamental to who they are. We must be cautious of giving messages to children especially that medicine considers them “broken”– since no child should be made to feel that way. On the other hand, should an ND proponent insist that autistic children should not be taught to better navigate the world into which they were born, then they are being ridiculously unpragmatic. Also, if they are incapable of recognizing that some cases of autism, like your own, may respond well to medical treatment and lead to better quality of life, then they are likewise being stubborn and blind. While I’m all for accommodations, we cannot expect the entire world to change. And so why would we not teach these children how to speak, socialize, read, and write when we expect typical children to do the same? We must try. –So, anyways, long story short: I am a proponent of both camps in moderation, because I see value in some of their respective messages. And I wish we were all spending more time seeking out those commonalities than arguing and dividing our efforts. This whole battle has become far too politicized for my taste. I love my husband, but I won’t say I agree whole-heartily with his viewpoint, which he well knows. Nor do I support extreme ND views. I prefer the middle road and I basically try to keep my head down and focus on the biology. 😉

  2. Pingback: A Time Window for Treating Autism? | Cortical Chauvinism·

  3. Like Johnathan Mitchell,I have been banned from both Wrong Planet,and Aspies For Freedom.This was about ten years ago.I had just had another major regression,as a result of an acute case of meningitis.I was just starting to study all of the medical literature around autism,and had no real idea of the range of the spectrum,and how it effected people.

    Unlike Johnathan,I did not blatantly ask people if they wanted a cure,what I did,at both places,was to simply tell my story.All my medical issues,and regressions.My developmental delays,behavioral problems,learning disabilities,and deficiencies in daily functioning,and I asked if there was anybody else there like me.

    Both places went wild.They had never heard of a case like mine,I’ll get to that.At both places,I was accused of making up my story,to scare them into wanting a cure.That accusation stunned me.I was not aware anybody could be that devious,

    It was not until a while later,when I discovered the old Autism Research Institute Yahoo! group.The people there were very helpful.I learned a lot,and was given a lot of help as far as getting the right tests.

    One thing I have noticed about most advocates of neurodiversity,is they are woefully ignorant about all of the advances in autism science,and have no interest in learning.This is something I follow intently.This gets to what you say about neurodiversity advocates being stubborn and blind.When you talk to a lot of neurodiversity advocates about what autism is,you may as well be talking to someone from the 1970s.It’s very frustrating.

    • I agree. In my time at WP and similar forums, I noticed a lot of people talking about things they really didn’t know much about, and what’s worse: they fought tooth and nail for those opinions. In truth though, I noticed that coming more from younger members (although not always), whereas the older members tended to be more measured and were better at listening and sharing ideas. (My own forum attracted some of these older members and we built a nice cozy warm community for ourselves that lasted a good 6-7 years.) So in part I wonder if some of the “personality” of WP isn’t itself defined by the younger ages of its membership. The nature of youth, after all, is often defined by its ignorance and its lack of awareness of that ignorance. I know for me at least, I grew away from ND, of which I was originally a proponent, as I went through my graduate training etc. and learned more and more biology– realizing there were so many areas I was originally ignorant of but thought I knew well. And also having more opportunities to talk with parents, especially who have kids who are more severely affected. I feel more sympathy now understanding that it’s difficult enough raising a typical child, but raising one who requires 24/7 supervision can be exhausting. I can’t imagine I would fair much better in their situations. On the other hand, I do understand that the concept of ND gives a kind of mental permission to a group of people who, let’s face it, have usually been treated as social outcasts. So it gives them back some sense of pride and belonging. I know for myself, for a time while I was new to my diagnosis, it made me feel more okay about myself because some parts of ND can be very positive. But it has also become a tool of the communities who use it, and some of those people have very extreme ideas indeed. In truth, I think most ND proponents have only vague ideas of what ND is. I know that was the case for me and for many others I interacted with. Most don’t know the term’s history. Which makes it all the more ironic that people are fighting over it! They don’t even know what they’re fighting for. I have also tried to convince my husband, to little avail, that most ND proponents don’t know what they’re supporting but only have vague communal ideas as to what it’s all about. They’re following the online herd. But he tends to approach most proponents as though they’ve written whole books on the topic, haha! In reality, that’s far from the case. Ultimately, as a scientist, I think ND’s biggest flaw is trying to be a theory of biology without knowing much biology. That therefore makes it a cultural movement and certainly not a scientific one. And without the biological component, I don’t know how useful it is in helping improve the lives of those on the spectrum.

  4. I think neurodiversity people would be a lot more widely accepted,and tolerated,if they were to say that they speak for a select group of the very high functioning,rather than everybody with an autism diagnosis.What Harold Doherty used to call “the royal we” in his old blog.Given the wide range of severity and comorbidities in autism,I am not sure how neurodiversity can even work as an idea,unless you exclude most people with a diagnosis.

    John Elder Robison is probably the lone voice of sanity in the whole neurodiversity movement.And even he seems to struggle as to how neurodiversity might include everybody.

    • Yeah, for all its inclusivity, it’s not very inclusive. :/ And in truth, I suspect some of the flaws of the ND movement reflect the fact that auties are not always known for our theory of mind and our cooperativeness, so it’s that much more of a challenge to seek middle ground. Mind you, I don’t find parents chelating their children to death all that more reasonable, haha. Although I can understand to some extent their desperation. But some parent groups have their fingers plugged as far into their ears as some ND proponents. And that opposition has driven both groups to greater extremes. Emotional investment in an idea can make one blind to viable alternatives.

      I agree, John tries. I like him very much. And were he the face of ND in its entirety, I imagine much of the conflict wouldn’t exist. In fact, I have heard some proponents, such as my friend, Wenn Lawson, speak about ND ideas quite movingly and eloquently. And again, were that the face of ND, few would take issue. But there has been a lot of animosity and argument coming from both sides and it’s sullied the movement extensively. In short, bad bad PR.

Leave a Reply

Please log in using one of these methods to post your comment:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s