Archives for category: Autism

By creating genetically engineered fish, two independent groups have identified genes in an autism hotspot on chromosome 16 that influence head size and brain development. One of the studies appears today in Nature.

A 29-gene stretch of chromosome 16 known as 16p11.2, or 16p, is deleted or duplicated in roughly one percent of individuals with autism and duplicated in some individuals with schizophrenia. Researchers have struggled to sort out which genes in the region contribute to features of these disorders.

Using zebrafish allows for an unbiased screen of individual genes, says Nicholas Katsanis, professor of cell biology at Duke University in Durham, North Carolina, and lead investigator of the Nature study. “We tested all of them with exactly same protocol, with no prior expectation of what we were going to find,” he says.

His study shows that suppressing a little-known gene called KCTD13 in zebrafish leads to a 20 percent increase in head size. Conversely, expressing too much of the gene leads to a 20 percent decrease in head size.

This seems to mirror what happens in people. Individuals lacking one copy of 16p often have abnormally large heads, dubbed macrocephaly, whereas those with an extra copy tend to have abnormally small heads, or microcephaly.

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SFARI, May 2012.

When I want to learn about a certain drug treatment, I typically begin with a search for mentions of the compound in the scientific literature. If I find a lot of studies, or even a handful, that report that it works, I usually come away thinking that it’s at least a promising candidate.

The trouble is, researchers rarely publish accounts of a drug failing. And according to a study published last week in Pediatrics, this publication bias is making antidepressants look like a better option for treating autism than they really are.

Although antidepressants have not been specifically approved by the U.S. Food and Drug Administration to treat autism spectrum disorders, many physicians prescribe them ‘off-label’ to alleviate the repetitive behaviors that are one of the disorder’s core features. An estimated 15 to 25 percent of children with autism take a popular type known as selective serotonin reuptake inhibitors, or SSRIs, such as Prozac or Celexa.

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SFARI, May 2012.

Children with autism carry twice as many new and damaging genetic mutations as typically developing children, according to a large study published today in Neuron.

Michael Wigler, professor at Cold Spring Harbor Laboratory in New York, and his collaborators sequenced the exome, or protein-coding parts of the genome, using DNA isolated from blood cells from 343 children with autism and their family members. The findings lend statistical heft to three other exome-sequencing studies published inNature earlier this month.

“This fourth Musketeer is the largest of all four, and really puts the nail in the coffin” regarding the abundance of damaging mutations in autism, says Jonathan Sebat, associate professor of psychiatry and cellular and molecular medicine at the University of California, San Diego, who was a postdoctoral fellow in Wigler’s laboratory but was not involved in the new work.

The new study, as well as two of the older papers, tapped into the Simons Simplex Collection (SSC), a genetic and medical repository of some 2,700 families with only one child with autism and unaffected siblings and parents.

Unlike the other three papers, the new one also identified intriguing genetic links between autism and fragile X syndrome, the most common inherited form of intellectual disability. An estimated one-third of children with fragile X are also diagnosed with autism.

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SFARI, April 2012.

Several hundred genes are likely involved in autism, according to the latest trio of studies looking at the genomes of children with the disorder. But let’s not forget that one of the most intriguing genetic links has been known for decades. Autism affects four times as many boys as girls. And at the level of DNA, there’s only one difference between the sexes: Girls have two X chromosomes, boys an X and Y.

So why don’t we hear more about that Y?

The male chromosome only carries about 60 genes, of which 2 have been linked to autism. Nevertheless, some new research on children born with extra sex chromosomes suggests that there may be more than meets the Y.

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SFARI, April 2012.

Children with autism don’t follow certain grammatical rules, according to one of the few studies of the disorder from the field of linguistics.

Autism’s bafflingly diverse array of language deficits — from word repetition to unusual syllable stresses to speaking in a monotone or sing-songy voice or not at all — has always been a hot topic of research. But the vast majority of studies in the past 30 years have focused on semantics, or the meaning of words, and pragmatics, the way that intentions, implications, history and other subtle social contexts affect meaning.

In contrast, the new study, published online 21 March in Applied Psycholinguistics, is one of a handful to look at autism and syntax, or the rules that govern how sentences are structured. The researchers found that children with autism don’t understand reflexive pronouns such as ‘himself’ and ‘herself.’

“What we’re arguing here is that autistic kids have some real grammatical deficits, not just communication deficits,” says lead investigator Ken Wexler, professor of brain and cognitive science at the Massachusetts Institute of Technology.

This distinction is important, he adds, because many computational linguists, including Wexler himself, believe that grammatical abilities are controlled by specific, innate structures in the brain, whereas semantic and pragmatic skills are more complicated and learned over time. Sorting out which deficits are common in autism could shed light on the brain systems derailed in the disorder.

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SFARI, April 2012.

More and more researchers, it seems to me, are trying to peek into the minds of children with autism by analyzing how they put together a sentence.

Language impairments are one of the most common features of autism. But linguists have long debated the precise nature of the disorder’s language deficit. Do grammatical errors mean there’s something wrong with the language centers of the brain? Or are they instead the indirect result of an individual’s social problems? Two new studies support the latter idea.

Helen Tager-Flusberg‘s work in the 1980s first suggested that social aspects of language are behind all grammar problems in people with autism. One of her experiments, for example, focused on ‘wh-questions’ — such as ‘What did he eat?’ and ‘Who does Mary like?’ — which are interesting because they can indicate a child’s desire to begin a conversation or attract the attention of others. Tager-Flusberg found that children with autism ask fewer wh-questions than do children with Down syndrome, but the questions coming from children with autism are more grammatically correct.

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SFARI, March 2012.

Children with autism who have different verbal and intellectual abilities seem to glean useful social information from different parts of the face, according to the largest-ever eye-tracking study of the disorder.

These differences suggest that children with autism adapt to their environment based on their specific strengths and weaknesses, the researchers say.

The findings, published in the March issue of the Journal of the American Academy of Child and Adolescent Psychiatry, illustrate both the importance and the challenges of studying differences among people with autism.

“Different people have different compensatory strategies to navigate the demands of social life,” says lead investigator Ami Klin, chief of the division of autism and related disorders at Emory University School of Medicine in Atlanta.

Experts applaud the study for taking an approach that’s only beginning to gain traction in the autism field: parsing the notoriously diverse disorder into smaller groups of children that share a particular trait, such as verbal ability. Doing so could help pinpoint new imaging or genetic biomarkers, and could help clinicians choose effective treatments, researchers say.

“The study highlights that any interventions that are used need to be specific to the child in question,” says Gwyneth Doherty-Sneddon, professor of psychology at Northumbria University in the U.K., who was not involved with the new study. “There are important individual differences, so an intervention that might work well with one group of children is not going to work well with another group.”

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SFARI, March 2012.

We’ve learned a lot in the past few decades about how brain connections in children with autism go awry during early development, and the genetic and environmental factors that contribute to these changes. Veteran autism researchers often quip, “We’ve come a long way from refrigerator mothers,” referring to the notorious theory from the 1950s that cold, unaffectionate mothering causes the disorder.

In France, however, much of the psychiatric establishment has not moved on.

At least, that’s the message of Sophie Robert’s documentary film, Le Mur (The Wall), which purports that four out of every five psychologists in France follow Sigmund Freud’s psychoanalytic method and shun biological explanations for autism. Their ignorance is shocking and almost comical, except that it’s preventing thousands of children with the disorder from accessing behavioral therapies.

Over the course of four years, Robert interviewed 30 psychiatrists and psychoanalysts in France regarding their beliefs about autism, and followed one family that has two boys with the disorder and was searching for help. One of the boys, Guillaume, showed marked improvements in speech after his parents began behavioral intervention — the very approach eschewed by analyst after analyst. Autism, the analysts insist, is the result of ”la folie maternelle,“ or maternal madness, and the best way to treat it is to remove the child from her care.

The film was released online last September, prompting outrage from the psychologists who were featured in the film, as well as their colleagues. Three sued Robert for allegedly misrepresenting their views through editing. Then last month, a court ruled in their favor, censoring the film until Robert removes their interviews and pays more than 30,000 euros in damages and fees. Robert, who denies taking the interviewees’ comments out of context and says they all signed detailed releases, is filing an appeal.

The uncut film is still available online with rough English subtitles. (See this site for a handy transcript.) But even with the poor translation, it’s easy to see why these psychologists — most of whom are in their later years — are embarrassed by the way they’re portrayed.

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SFARI, February 2012.

The development of white matter tracts, the nerve bundles that join one brain region to another, is different in babies who go on to develop autism compared with those who do not, according to a new study.

Researchers scanned the brains of infant siblings of children with autism — who have an increased risk of developing the disorder themselves — several times during their first two years of life. The so-called ‘baby sibs’ who go on to receive a diagnosis of autism at 24 months of age have distinct brain patterns at 6 months and abnormal neural development from 6 to 24 months, according to the study. The results were published 17 February in the American Journal of Psychiatry.

“The story is that autism is an unfolding process, not something that happens in the third trimester and then is done,” says lead investigator Joseph Piven, professor of psychiatry at the University of North Carolina-Chapel Hill. “We see the brain changing over time in a dynamic way.”

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SFARI, February 2012.