Autism

I worked with a guy who had Asperger syndrome. He was brilliant but strange. He never looked you in the eye and he had no social skills. Sadly his company was always nearly broke despite his brilliance because he couldn't find people to surround himself with the necessary skills.

I've been interested in autism since the early 1970s when I reviewed a book on it that claimed it was caused by a "refrigerator mom". Thankfully that era is long gone.

Here's a bit from a nice piece about current research at Stanford from the alumni magazine:

[Autism is] a disorder that affects 1 in every 110 kids. (The rate is 1 in 70 for boys and 1 in 315 for girls.)

Autism is a spectrum of disorders that share three core features—language deficits, social deficits, and repetitive interests and movements. On one end of the spectrum are people with Asperger's syndrome, who are socially awkward but who often have above-average intelligence. Dolmetsch's son has this diagnosis: He was late to speak and when he did speak, he talked in a stilted and peculiar way—more like a little adult than a child; and he has problems socializing. The most serious autism cases involve severe mental disabilities (about 40 percent of children with autism have IQs below 70) and behavioral problems. Between these two extremes, children may have normal intelligence but pronounced language and social impairments.

This is fascinating because it uses identical twins -- the gold standard for separating genetic versus environment -- who show different traits:

J.C. Flores, '87, has 15-year-old identical twins with autism. Lomasi can speak, but she avoids talking and gives mostly one-word answers. Marielle can say only a few words and has no functional communication system. "They're sweet and they like to hang around people," Flores says. "But they don't really feel the need to communicate. They don't see why you have to." ...

Studies of twins have shown that autism has a large genetic component, but it's not all genes. Identical twins have the same DNA, but sometimes only one twin gets autism. In other cases, as with Flores's daughters, Lomasi and Marielle, the severity of the disorder differs. The genetics are also complex. Different genes may be involved in different people; and, in any given individual, the disease may arise from changes in one gene, changes in several genes, or a combination of genetic and environmental factors. (Though no specific environmental triggers have been identified, researchers are testing everything from exposure to heavy metals and pesticides to TV watching.) Tackling this complexity requires large studies.

I'm amazed at the progress in identification and understanding "the disease", but research is nowhere near understanding what causes "it":

One of the biggest challenges is that autism is not one thing: It's a catchall diagnosis that likely includes a host of biologically distinct disorders. Though children with autism share a set of symptoms, these symptoms are quite varied and may have many, diverse biological origins. "Autism is incredibly heterogeneous. We've been lumping everyone together under this name autism, and unfortunately it makes it very difficult to study the biological features when we are treating multiple groups as one," says Sophia Colamarino, '90, vice president of research for Autism Speaks—a science and advocacy group—and consulting associate professor of psychiatry and behavioral science. To get a toehold into the biology, researchers will need to identify unique subgroups of autism, she says. Researchers across the globe are defining subgroups based on genes, molecular pathways, or signatures in the brain and blood.

Another impediment: access to the brain. Scientists can slice cancer cells out of a tumor and study them directly, but they can't just scoop cells out of the brain. Stanford is on the forefront of solving this problem...

This bit about the advances in genetic understanding is fascinating:

In the past decade, geneticists have discovered a handful of genes that when mutated or missing can cause autism. Though rare, these genes have given scientists some of their best clues about the disease's biological underpinnings. "I think it's very exciting, even if it's rare cases. We can at least get a better understanding of one piece of the puzzle and then we can branch out from there," Hallmayer says. For example, several of these genes are involved in communication between neurons. In a 2010 paper in Nature, Hallmayer and his colleagues from the Autism Genome Project greatly expanded this list of genes—reporting hundreds of rare genetic events that may be involved in autism.

It's long been known that about 5 percent of autistic kids have a chromosomal abnormality that can be seen under a microscope —part of a chromosome is missing, duplicated or in the wrong place. Because these changes affect a large number of genes, the children often have many problems in addition to autism. What wasn't known until recently is that we all have slight imperfections in our chromosomes—small regions of DNA that are duplicated or deleted. When these stretches of DNA contain genes, people can end up with one or three copies of the genes instead of the standard two. Technological advances have made it possible to detect these "copy-number variants," or CNVs. And it turns out they're important in autism and some psychiatric disorders. For example, a region of chromosome 16—containing about 25 genes, some involved in brain function and development—is deleted or duplicated in 1 to 2 percent of people with autism (and some with schizophrenia). Scientists are beginning to study these patients as an autism subgroup. ...

They identified disruptions in hundreds of genes that occurred only in autism cases, never in controls. Not all of the genes will turn out to be relevant to autism, but the ones that are could explain maybe 10 to 15 percent of cases, Hallmayer says.

This article is full of bits of information, hints about various things that cause autism. It is quite complex. There are lots of possibilities. It is easy to agree that this is a "spectrum" disorder because there are so many different areas where an autistic brain differs from a normal brain. This bit is surprising:

It's long been known that children with autism have larger-than-normal brains early in their development. Hardan has refined this observation, showing that some (but not all) children with autism have an increase in the thickness of the cortex —the part of the brain responsible for complex functions such as language and social behavior—that disappears as they grow. It might be possible to link this back to genetics, says Hardan, who frequently collaborates with Hallmayer. We know some of the genes that contribute to cortical thickness, he says.

Hardan is exploring new brain imaging technologies that offer an unprecedented level of detail. For example, diffusion tensor imaging (DTI) shows the individual axons (the elongated parts of neurons) that connect different parts of the brain. And MRI spectroscopy measures the levels of specific chemicals in various parts of the brain. DTI studies from several universities suggest that autistic children have abnormal long-distance brain connections, an observation that dovetails with Dolmetsch's studies in neurons. Using MRI spectroscopy, Hardan also has detected specific chemical imbalances in the brains of children with autism. He's looking for treatments that can normalize these imbalances.

Hardan's team is involved in about 15 different clinical studies. Whenever possible, he tries to link treatment responses to changes in brain images and to a subgroup of people with autism.

I expect as neuroscience becomes more advanced there will be more splitting and the autistic spectrum will hive off new diseases. Unfortunately, because of ignorance, the disease is "diagnosed" by symptoms. But that really is backwards. If you understand the mechanism then you can identify the disease. Multiple diseases can confuse you by appearing to be one disease.

One researcher that I've followed for years is Simon Baron-Cohen at the Autistic Research Centre in the UK. He may be the modern equivalent of the "refrigerator mom" diagnostician. But I do like his "extreme male brain" approach to understanding autism.