Autism’s Plot

Erika wants to know about the state of autism research. “How is the field doing in terms of rigorous science?” she asks. “What is the most promising theory about how autism develops?”

The first question’s easy to answer: pretty damn well. In 2008 (the last time a good survey was done), autism research reaped $144 million in tax dollars and $78 million from private funds. That’s a helluva lot of interest in a disorder that is diagnosed in 1 percent of the population. In no small part because of this investment, autism science is constantly making headlines. In just the past month, seven gangbuster autism papers have come out in the likes of Nature, Nature Genetics, Science Translational Medicine and Neuron.

The other question, about smart theories of autism, is one I’ve been trying to sort out for awhile.* No answer is wholly satisfying, but I’ll tell you a bit about recent findings and how I see them fitting into a bigger picture. The short version: autism can begin with one of hundreds, if not thousands, of different glitches during fetal development, all of which eventually result in a similar kind of abnormal wiring in the brain. It’s like roots, separate yet impossibly tangled, which, with water, sun, and time, give way to an awesome, immutable tree.

If I had to choose one thing that’s responsible for the lack of understanding in autism, it’s the fact that none of the trees look the same — to the point where it’s difficult to pin down the essence of tree-ness. My metaphor is failing.

Here’s what I mean. Autism is defined by impaired communication, social problems and repetitive behaviors. Ideally, the diagnosis comes after a highly trained clinician observes a child for several hours and then checks off a sufficient number of little boxes under each of these three categories.

That system means that a boy who bangs his head on walls and does not speak and will never have a job might get put in the same psychiatric bucket as a gadget geek and bestselling author. As I’ve heard countless times from parents of children with autism and the scientists who study them: If you know one kid with autism, you know one kid with autism.

The behavioral diagnosis does imply, though, that there is some entity, called autism, that exists across this befuddlingly diverse group. Which finally brings me to what’s been so exciting about autism science in the past couple of years. With the help of genetic screens, protein analyses, brain scans and mouse models, scientists are finding some biological signatures that crop up in many individuals on the autism spectrum. And many (though not all) of those signatures have similarities that could (could) be used to develop effective treatments.

What are the signatures? I’m trying not to write the longest-ever LWON post, so I’ll just mention one famous old idea. It’s called the ‘connectivity theory‘ of autism, and it says that the autism brain has A) long-range connections (think between regions) that are too weak, and B) short-range connections (think within one region) that are too strong. Initially, the theory was supported by a few small studies in which researchers looked at postmortem brain tissue or brain scans of people with autism.

More recently, a growing number of groups have backed up the theory with genetic and molecular studies. They argue that abnormal connectivity across the whole brain stems from improper signaling between individual cells. The signaling is hugely dependent on the molecular make-up of the synapse, the junction between neurons. And the synapse, it turns out, is the star of many of the new papers.

For example, a study published last month found that synapse-related genes tend to be expressed at lower levels in autism brains compared with controls. (Gene expression is a way of measuring when and how DNA gets turned ‘on’ to make RNA and, eventually, proteins.)

In another study, published last week, researchers took a few proteins that are damaged in autism-related syndromes — such as fragile X, tuberous sclerosis and Phelan-McDermid — and investigated hundreds of other proteins that interact with them. They found that dozens of them work together in the dendritic spine, the part of the synapse that receives electrical signals.

To some readers, I suspect, none of this will seem all that exciting. The connectivity theory, like all of the others, has lots of holes. More poignantly, these exciting scientific advancements haven’t led to more than a handful of promising autism treatments. I feel cynical sometimes, too.

The situation is cheerier if you consider that many of the recent breakthroughs in autism came from molecular tools — such as fine-grained genetic screens — that have only been around for a few years. As the technology continues to improve, researchers should be able to describe more and more of autism’s myriad roots, and hopefully, eventually, its tree.

**

Images from Martin LaBar, via Flickr, and Wikimedia Commons

*Full disclosure: Since 2007, I’ve written frequently for SFARI.org, an autism news website supported by the Simons Foundation. The foundation gives large grants to the best and brightest in the autism field, and the investment has paid off in spades: much of the work mentioned above was funded by SFARI.

This post was originally published on The Last Word on Nothing