April 2 is
World Autism Awareness Day. I've already begun the day by engaging in a
twitter exchange with a mother of three autistic children who compared autism to a "car crash." I've been pondering what contribution--if any--I should make on World Autism Awareness Day. From my interior, insular world, it seems like everyone
knows about autism. It seems like every other
headline is about autism. I know that just about every other post I write for this blog is
about autism. Is everyone aware of autism? What do you know about it?
That's a complex question. Do you know about autism from watching the TV show "
Parenthood"? Are you aware of its existence because of the media attention or the
blue puzzle pieces at Toys 'R' Us or
blue light bulbs at Home Depot or
blue avatars anywhere on social media? That may make you aware of the concept, just as a
pink ribbon vaguely resonates in our social consciousness as being associated with breast cancer. It may mean that you know
of autism. But what do you really
know about autism?
That's an even more complex question. My lovely friend, autism parent, and all-around one of the greatest people I know,
Shannon Rosa, has
defined the cornerstone of what anyone needs to know about autism.
All behavior is communication. We all--parents, educators, autistic people, researchers, the news media--we all need to grasp that. The interaction of our endocrine systems with our nervous systems produces behaviors, and our behaviors carry meaning, they communicate something to those who are paying enough attention. It may not be intentional communication, but the messages are there. What's lacking for many people is a code breaker for what that message is.
Rosa's cornerstone of autism awareness is an outward manifestation of an inner machinery that remains, dare I say, a puzzle. The problem with this particular puzzle is that people have gone out of their way--and continue to do so--to grab puzzle pieces from boxes that have nothing to do with autism and try to force them into the growing picture of what underlies this developmental difference. Others who are more cynical use these distractors to make money for themselves or simply to gain attention. These
distractors are an enormous time and
resource suck, and extricating them from the puzzle where they have no place is an arduous process.
Given these distractors, it's no wonder that progress on the true underpinnings of the group of developmental derailments we call autism has been glacial. Autism is likely the endpoint of many pathways, all leading to the outward communication and behavioral differences that we, in our need to categorize and encompass as much as possible, call Autism.
It's not alone in this complexity. If you've ever even glanced at the basics of the
neuroendocrine system (warning: hilarious image), you know that the interactions and pathways and molecules and possibilities are dizzying. Take this array of mechanisms that seems impossible to tease apart and add in likely environmental influences, and as I've noted before, we've got one of the
greatest neurological mysteries of our time on our hands. Thanks to this tangle of physiology and environment with a few obnoxious and persistent mechanistic red herrings thrown in, and yes, progress has been turtle like, at best.
So, where are we now? Now that we've made strides in shuffling off the burden of the
biggest distractor of a global vaccine etiology, where does that leave the science of autism?
In many ways, we find the science where everyone should have been looking all along: in the genes. Here's what to watch for in the science of autism in the coming years:
1.
Copy number variation (
CNVs). A disorder or developmental difference with this etiological complexity may come down to something as individually variable as the number of
copies of a gene sequence a person carries. Bob as five repeats in one area of his DNA, Sue has 10, Sue has autism, Bob does not. But when Bob has a child, by that time those repeats have doubled to 10 in his germ line (where his sperm comes from), and he passes 10 to his child. His child has autism. His next child gets a sperm that carries only 5 repeats and does not have autism. The neighbors all have between zero and four repeats, and none of them has autism. In other words, that saying that people use a lot with autism, "When you meet one person with autism, you've met one person with autism"? Could be more precise than we think.
2. Mitochondria. I've summarized a
large review of the state of the science for mitochondria and autism. These disorders also would carry a genetic component and confer susceptibility to an environmental trigger, such as a high fever, illness OR vaccine induced, that stresses the system.
4. Hormones. Behaviors arise from the interaction of your nervous and endocrine systems. A persistent hypothesis of a causative mechanism of autism spectrum disorders is that androgenization of some sort underlies the manifestions. I've blogged this before, offering a
different perspective: That low estrogen, rather than high androgen, could also be a plausible explanation. Just for the record, everyone, estrogens are not some kind of passive, default players in development and behavior. They're active, too, just like those "manly" hormones. The thing is, hormones act thanks to a genetic scaffold that allows reception of and response to their message. Even if hormones play a role, we still must look to the genes.
5. Then there's
epigenetics. Genes don't just sit there, naked and waiting for something to trigger their expression. Sometimes, cells actively put genes into shutdown mode, hushing them up with chemical tags that make the sequences unavailable for use. This tagging is the basis of epigenetics, or regulation above the level of the gene. We acquire tagging from our parents--which they've both acquired from their parents and during their lifetimes--and we modify our own tagging through our lifestyles and propensities. In essence, these tags can have the same effect as a mutation.
As you can see from this list, so much remains to be done.
Genome-wide association studies, which provide a snapshot of the big picture of gene expression, help researchers group together genes that seem to team up in people with autism vs. people without it. The harvest from such studies is likely to be huge, and the hours and dollars and intellectual investment that these results will require is almost as overwhelming as the autism mystery itself.
What can you do, on this day or any other day, to advance our understanding of the causes of autism? You can do one or both of two fundamental, useful things.
1. If you donate on behalf of autism research, donate to a foundation that focuses on studies like those I've mentioned above. Real science looking at real possibilities. The
Autism Science Foundation.
2. Wherever you are, wherever you go, if you see a person behaving "oddly" or a child having a "meltdown" that makes you think to yourself "brat," try to remind yourself of the following: All behavior is communication.
Selected references, in no particular order:
Autism Res. 2011 Feb;4(1):5-16. doi: 10.1002/aur.175. Epub 2011 Jan 5.
Behavioral profiles of mouse models for autism spectrum disorders.
Ey E, Leblond CS, Bourgeron T.
Am J Psychiatry. 2010 Dec;167(12):1508-17. Epub 2010 Oct 15.
Feyder M, Karlsson RM, Mathur P, Lyman M, Bock R, Momenan R, Munasinghe J, Scattoni ML, Ihne J, Camp M, Graybeal C, Strathdee D, Begg A, Alvarez VA, Kirsch P, Rietschel M, Cichon S,Walter H, Meyer-Lindenberg A, Grant SG, Holmes A.
J Am Acad Child Adolesc Psychiatry. 2010 Aug;49(8):794-809. Epub 2010 Jul 3.
Grafodatskaya D, Chung B, Szatmari P, Weksberg R.
Science. 2007 Apr 20;316(5823):445-9. Epub 2007 Mar 15.
Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T,Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M.
Hum Mol Genet. 2011 Mar 25. [Epub ahead of print]
Fassio A, Patry L, Congia S, Onofri F, Piton A, Gauthier J, Pozzi D, Messa M, Defranchi E, Fadda M, Corradi A, Baldelli P, Lapointe L, St-Onge J, Meloche C, Mottron L, Valtorta F, Nguyen DK,Rouleau GA, Benfenati F, Cossette P.
Hum Genet. 2011 Mar 22. [Epub ahead of print]
Gauthier J, Siddiqui TJ, Huashan P, Yokomaku D, Hamdan FF, Champagne N, Lapointe M, Spiegelman D, Noreau A, Lafrenière RG, Fathalli F, Joober R, Krebs MO, Delisi LE, Mottron L, Fombonne E, Michaud JL, Drapeau P, Carbonetto S, Craig AM, Rouleau GA.
Autism Res. 2010 Dec;3(6):303-10. doi: 10.1002/aur.158.
Salyakina D, Ma DQ, Jaworski JM, Konidari I, Whitehead PL, Henson R, Martinez D, Robinson JL, Sacharow S, Wright HH, Abramson RK, Gilbert JR, Cuccaro ML, Pericak-Vance MA.
PLoS Genet. 2011 Feb;7(2):e1001318. Epub 2011 Feb 24.
Myers RA, Casals F, Gauthier J, Hamdan FF, Keebler J, Boyko AR, Bustamante CD, Piton AM, Spiegelman D, Henrion E, Zilversmit M, Hussin J, Quinlan J, Yang Y, Lafrenière RG, Griffing AR, Stone EA, Rouleau GA, Awadalla P.
Personally I am less interested in the state of the art vis-a-vie the causes of autism as opposed to developing workable on-the-front-lines treatments for autism and making them available to all who need them. Yes, knowing a cause can sometimes help determine a cure, but we have to work on both sides of the problem at once. To be blunt, I don't care if autism is caused by stepping on a rusty nail, I need to know how to help my son NOW.
ReplyDeleteThere are workable front-line treatments for autism. They're called early intervention and therapies. If course they should be made available to all who need them, but this is a science blog and that post is my autism and science post. I have a personal blog where I talk about the day-to-day needs of autism families.
ReplyDeleteIdentifying the cause for anything is generally the first step toward finding ways to ameliorate it at the physiological level. As a scientist and an autism parent, I do care about what causes it, in part because my interest is not confined only to my own child.
Thankyou so much for this concise overview of where the current research focus is. Trying to keep up with, and understand the studies that abound when you do not have a background in science is difficult. These articles help those of us who are genuinely interested but lacking in expertise to keep abreast of developments. You always explain science so beautifully Emily. Thank you.
ReplyDeleteI was intrigued by your mention of hormones, especially since my son, who has autism, was also born with stage 3 hypospadias. Not being a scientist, it is incredibly difficult for me to read the research on these two things and try to see whether there are any commonalities.
ReplyDeleteInterestingly enough, one thing "awareness" has done is that people don't flinch too much if I say the word autism, but you rarely find anyone who has heard of hypospadias and even fewer who are comfortable talking about it.
Sorry if this is an off-topic comment. I have been thinking about this a lot since we have told my son about his autism diagnosis since he was asking questions about being different, but we have not talked about the hypospadias yet. It think I need to start the conversation but I am fearful to bring up something that isn't even on his radar yet.
It's not off topic to me. I did my postdoc researching the causes--genetic and environmental--of hypospadias. We have two children who have urological abnormalities, including one case of cryptorchidism. I once did an informal poll on my personal blog about urological abnormalities and autism, and quite a few people reported that their children had them.
ReplyDeleteHypospadias likely has a genetic component, but it also likely has an environmental component related to androgen inhibition or estrogen action. I'd be happy to try to answer any specific questions you may have if you want to email me at ejwillingham. It's an address at the mail of google, as one of my Field of Science colleagues would say. In other words, you've found someone who is incredibly comfortable talking about hypospadias, one of the most common of the congenital abnormalities.
I wanted to say thank you for the reply and I do plan to email you. Things have gotten a bit hectic with my son having some increased aggression, so I have been focusing on just getting us through each day.
ReplyDeleteMention of hypospadias in relation to autism has me wondering if there are any other genitourinary abnormalities associated with aspergers/autism. I'm a woman with Aspergers with some sexual dysfunction (anorgasmia) and possible morphological abnormailty. Have you heard this from any other women? It's not something I've ever brought up with a medical doctor, since it's hardly life-threatening. Just one of those oddities about myself I intuit could be related to the hormonal or endocrine differences in people on the spectrum.
ReplyDeleteThanks for writing this amazing blog.