Autism

Researchers collaborate on two large studies identifying the genetic basis of autism

Two new studies exploring the genetic basis of autism tie mutations in hundreds of genes to the disease.

Several teams of researchers collaborated on the studies, both published in the journal Nature, and found that about 60 of the genes are considered “high confidence,” meaning there’s a 90% chance that mutations within those genes contribute to risk for autism. Both studies show through genomic sequencing that many of these mutations are de novo, meaning that parents do not have the gene mutation, but they present spontaneously just before a child is conceived in either the sperm or egg.

It’s long been believed that autism is genetic, but a lack of large studies and advanced genomic sequencing has precluded any sort of consensus about what genes might be at play. But in the last couple years, scientists have been able to look at the genetic mutations in hundreds of people with autism and identify genes that likely factor into a child’s development of the disorder. In the two new studies, scientists were able to expand their work and look at thousands of people.

In one of the studies, several institutions used data from the Simons Simplex Collection (SSC), which is a collection of DNA samples from 3,000 families. In each of the families, one individual had autism. The researchers compared the gene sequences of the individual with autism to their unaffected family members. After analysis, they estimated that de novo mutations contribute to autism in at least 27% of families, where only one member has the disorder.

The other study, by researchers at 37 different institutions as part of the Autism Sequencing Consortium, looked at 14,000 DNA samples of parents with affected children. It found 33 genes the researchers say definitely increase risk for autism, should there be a mutation.

Even though there may be hundreds or even thousands of genes that contribute to a child’s risk of developing autism, the researchers on both studies found that the mutations appear to converge on a much smaller number of biological functions, like nerve-cell communication or proteins known to cause inherited disability. “In my view, the real importance of these studies is not diagnosis, and it’s not figuring out exactly what percentage of people have de novo mutations, it’s about laying the foundation to transform the understanding of the biological mechanisms of autism,” says Dr. Matthew State, chair of the psychiatry department at University of California, San Francisco and a co-leader of the SSC study, as well as a senior participant on the other study.

State doesn’t believe that the findings will mean that families will one day get their genomes sequenced to spot hundreds of possible mutations. Instead, they could lay the groundwork for discovering how autism develops, and what potential treatments, or even drugs, could help fight it.

Parents can learn how to give effective therapy to their children with autism, a new study in the Journal of Child Psychology and Psychiatry finds.

Researchers at Stanford University looked at a type of therapy called Pivotal Response Training (PRT), which is one the of the handful of treatments shown to be effective for kids on the autism spectrum, says Kari Berquist, PhD, study co-author and a clinical instructor in psychiatry and behavioral sciences and an autism clinician at Lucile Packard Children’s Hospital Stanford. The therapy focuses on improving kids’ motivation language skills by reinforcing their use of language related to the task at hand. One of the advantages is it can be done anywhere: anytime a child attempts to ask for something by name—a toy, say—they’d be rewarded with the item they requested, which reinforces their use of language.

They enrolled a group of parents of 53 autistic children between ages 2-6 in either a PRT course, which taught parents how to do the therapy with their kids, or a psychoeducation group, which taught general autism information. The children joined their parents for several sessions.

Researchers found that after just 12 weeks, 84% of parents were able to learn how to give effective PRT, and the children in the PRT group made significantly more progress than the other group in use of language and how often they were communicating.

“Group models are very new to autism treatment,” says Berquist, but the study shows that they can be effective while also being cheaper and coming with a built-in social support for parents. “I think this really allows us to get more people at once, to give more services at one time.”

The study was "interesting and important" but ultimately too small to make a clear link, one medical researcher said

A broccoli sprout compound may help with behavioral problems in some people with autism, a new study suggests.

Though the short-term study was small and did not see improvements in a third of the participants, it was still “promising” according to the lead researcher, CBS reports.

“This is just one study, and it’s a preliminary study,” said Dr. Kanwaljit Singh from Massachusetts General Hospital for Children.

44 boys and men with autism between the ages of 13 and 27 took part in the study. Some received sulforaphane, a compound found in broccoli and other vegetables that has previously been studied for its health benefits, while others received a placebo.

The compound was chosen because it can help trigger a heat-shock response, a series of biological events that protect cells from stress during fevers; some people with autism have been known to see improvement in regard to repetitive behaviors, for example, during fevers. Around 80 percent of the participants had a history of experiencing the “fever effect.”

Within four weeks of the 18-week study, parents were already seeing improvements in areas of communication, hyperactivity and irritability. Researchers, unaware of which participants were receiving a placebo, noticed similar changes. By week 18, roughly half of the sulforaphane participants had better social interactions, and, four weeks after the study and the sulforaphane stopped, such improvements were less apparent.

The head of medical research for the organization Autism Speaks, Dr. Paul Wang, said the study was “interesting and important” but ultimately too small to tell for sure whether the compound can help with autism treatment.

[CBS]

Unique EEG fingerprints reveal how autistic brains process sights and sounds

Diagnosing autism as early as possible, even before the first noticeable symptoms of social and developmental delays emerge, is becoming a critical strategy for reducing the condition’s most severe symptoms. Experts have long known that children with autism process sensory information – sights and sounds in particular – in different ways than unaffected children.

In a new study published in the Journal of Autism and Developmental Disorders, Sophie Molholm, from the departments of pediatric and neuroscience at Albert Einstein College of Medicine, proposes that those differences may lay the foundation for social and communication deficits in some children later on.

Molholm and her team took electroencephalogram (EEG) readings from more than 40 children aged six years to 17 years diagnosed with autism and compared their patterns to those of unaffected children of similar age and other characteristics. All children were given either a flash cue, a beep cue or a combination of both, and asked to press a button when these stimuli occurred. A cap with 70 sensors picked up the children’s brain responses every two milliseconds during these tasks, including those that recorded how the brain first processed the sensory information.

MORE: Behavior Therapy Normalizes Brains of Autistic Children

The children with autism showed a distinctly different brain wave signature from those without the condition. Specifically, the signals in those with autism showed differences in the speed in which the sights or sounds were processed, and in how the sensory neurons recruited neighbors in more far-flung areas of the brain to register and make sense of the information. And the more abnormal this multi-processing was, the more severe the child’s autistic symptoms. “By developing this tool in the older cohort of children we can then figure out which ones are the most promising and then go test them in younger children,” says Molholm.

It’s also possible that because the children she studied were older, the differences in their EEG patterns were the result of autism, rather than a sign of changes that precede the disorder. But, she says, “If you ask me to make an educated guess, I would say these are part of autism, and they represent neuropathology related to having the disorder. It seems unlikely to me that you get autism and then develop atypical auditory processing.”

MORE: Autism Symptoms Disappeared With Behavioral Therapy In Babies

Molholm says the sample was too small to use the profile for diagnosing autism, but it could lead to such a test if the results are confirmed and repeated. To confirm the findings, scientists will have to intervene with behavioral strategies for helping the different regions of the brain work in a more coordinated way when confronted with visual and auditory cues. If that reduces autism symptoms, then EEG profiling could become one of a number of new ways that doctors can start identifying those at highest risk – however young — of developing autism.

A paper that claimed government scientists covered up data showing a connection between vaccines and autism has been pulled by its publisher

Earlier in August, the journal Translational Neurodegeneration, an open access, peer-reviewed journal, published a re-analysis of a 2004 paper published in Pediatrics that looked at MMR vaccines and autism. The re-analysis of the data, by biochemical engineer Brian Hooker of Simpson University, claimed to find a higher rate of vaccination against MMR among a subset — African-American boys — of the original study population who developed autism than among those who did not, a finding that Hooker claims was suppressed by the authors of the original paper from the Centers of Disease Control. One of the co-authors of the 2004 paper, William Thompson, released a statement admitting to omitting the data after a secretly recorded conversation he had with Hooker was released on YouTube. (Thompson was not available for comment.)

MORE: Whistleblower Claims CDC Covered Up Data Showing Vaccine-Autism Link

Now, however, the editors of Translational Neurodegeneration have retracted Hooker’s paper, noting on its site that “This article has been removed from the public domain because of serious concerns about the validity of its conclusions. The journal and publisher believe that its continued availability may not be in the public interest. Definitive editorial action will be pending further investigation.”

The claim, however, may just be more unsubstantiated fuel from the anti-vaccination movement

If you haven’t noticed, there’s a war going on between those who believe in the health benefits of vaccines – that they can prevent deadly infectious diseases such as measles and polio – and those that believe that the immunizations do more harm than good. Now one of the authors of a 2004 government study that found similar vaccination rates among children with and without autism says the study omitted some important data.

The vaccine war is being fought on social media, in social circles and increasingly in doctor’s offices, as physicians are faced with doubts and questions from parents who find themselves being recruited onto the side of skepticism. Skepticism is healthy, and the sign of curious minds, but not when it flies in the face of evidence. Especially gold standard, rigorous scientific evidence that has been accumulating for decades and shows that vaccines are not linked with an increased risk of the developmental disorder.

William Thompson, a senior scientist at the Centers for Disease Control (CDC) and one of the authors of a 2004 study published in the journal Pediatrics, spoke with Brain Hooker, who serves on the board of Focus Autism (which was founded to “put an end to the needless harm of children by vaccination and other environmental factors”), about the data that was not included in the final report. The study looked at both healthy children and those with autism, to see if there were any differences in their rates of being vaccinated against measles, mumps and rubella (MMR), and found none. That suggested that childhood immunizations likely were not contributing to an increased risk of autism. Hooker and Thompson, however, discussed a subset of the 624 children with autism and 1824 without the condition who were studied and Thompson admitted that among African-American boys, the incidence of autism was higher among those who were vaccinated than among those who weren’t. But that information was not part of the paper. Thompson claims he was not aware that the discussion was being recorded, and his statements appeared in a video released on YouTube on August 22 entitled “CDC Whistleblower Revealed.”

Did the CDC cover up the data, as Hooker claims? A couple of things to keep in mind, both about the people behind the video and about how epidemiological studies like the one published in Pediatrics work (and explained in more detail in this article from Science-Based Medicine). For starters, the video was narrated by Andrew Wakefield, the British researcher responsible for seeding the questions about vaccines and autism in the first place. In 2010, the General Medical Council in the UK revoked his license to practice medicine and a year later, the journal that published his paper concluded that his findings were fraudulent.

Next, any time scientists take the original population of participants in a study, however large, and drill down to analyze trends in a subgroup – in this case the African-American boys – the power of the associations they find dwindles. That’s because the numbers get smaller, and in order to be statistically relevant – something known as statistical significance to statisticians – certain threshold numbers and confidence intervals for the connection have to be reached. In the 2004 study, the scientists looked at a smaller set of 355 children with autism and 1020 without for whom they had Georgia state birth certificates, which included additional information that might be relevant for any associations, such as birth weight, gestational age, and mother’s age, race and education. “This information was not available for the children without birth certificates; hence the CDC study did not present data by race on black, white or other race children form the whole study sample. It presented the results on black and white/other race children from the group with birth certificates,” the CDC notes in a statement responding to the video. Thompson claims that the findings were statistically significant, but results from smaller numbers of subjects still don’t hold as much weight as correlations found in the larger group.

In addition, it’s important to note that the study simply correlated age at vaccination and reports of autism, which says nothing about the direction of the connection. For example, the authors of the 2004 study note that “Case children, especially those 3 to 5 years of age, were more likely than control children to have been vaccinated before 36 months of age.” The association between vaccination and symptoms, however, was more likely due to the fact that the children had to be immunized in order to register in preschool, and doesn’t necessarily indicate that the shots contributed to the autism.

In a statement issued through his attorneys, Thompson says “Reasonable scientists can and do differ in their interpretation of information.” He calls for transparency in the data collecting and reporting process, but says that the way that the 2004 study was presented does not negate the importance of vaccination. “I want to be absolutely clear that I believe vaccines have saved and continue to save countless lives. I would never suggest that any parent avoid vaccinating children of any race. Vaccines prevent serious diseases, and the risks associated with their administration are vastly outweighed by their individual and societal benefits.”