Autism

The very first medical descriptions of autism, published in the 1940s, noted that children with autism don’t respond normally to human voices. Picking up on the nuances of spoken communication is especially difficult for those with autism: Even if they can speak and read, they often struggle to hold a back-and-forth conversation or understand emotional cues in others’ voices.

Now, new brain research from Stanford may explain why. Functional MRI scans showed that in kids with autism, brain regions specialized to respond to speech are poorly connected to the brain centers that process rewards and interpret emotions. The new study, which appears today in Proceedings of the National Academy of Sciences, also found that, for individual children, greater impairment in these brain connections translated into more severe communication deficits, as measured by the verbal portion of a standard test of autism severity.

From our press release about the new findings:

“Weak brain connectivity may impede children with autism from experiencing speech as pleasurable,” said Vinod Menon, PhD, senior author of the study.

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“The human voice is a very important sound; it not only conveys meaning but also provides critical emotional information to a child,” said Daniel Abrams, PhD, a postdoctoral scholar in psychiatry and behavioral sciences who was the study’s lead author. Insensitivity to the human voice is a hallmark of autism, Abrams said, adding, “We are the first to show that this insensitivity may originate from impaired reward circuitry in the brain.”

The findings could help scientists improve existing autism therapies or design new ones. Now that they know that these particular circuits are weak, they can use brain scans taken before and after a child receives an autism therapy to check whether the treatment strengthens the child’s brain.

Previously: A mother’s story on what she learned from her autistic son, New imaging analysis reveals distinct features of the autistic brain and New public brain-scan database opens autism research frontiers
Photo by Kevin Shorter

On Saturday, the Stanford Autism Center at Packard Children’s Hospital will host its sixth annual Autism Spectrum Disorders Update. During the day-long symposium, parents and caregivers will have an opportunity to discuss new autism research and interventions with physicians, as well as learn about the center’s clinical services and ongoing autism studies at the School of Medicine.

In anticipation of the event, we asked Carl Feinstein, MD, director of the center, to respond to your questions about issues related to autism spectrum disorders (ASDs) and to highlight how research is transforming therapies for the condition. Below he addresses a range of topics, including early diagnosis and intervention in infants and the role of environmental factors and genetics in contributing to autism.

AnneMarie asks: How meaningful are environmental factors, such as nutrition and exposure to toxins during pregnancy, in terms of autism risk?

During pregnancy, proper nutrition and taking reasonable measures to avoid exposure to known environmental toxins are basic steps an expectant mother, and family, can take to promote a baby’s health and minimize risks of medical problems for the newborn. This principle certainly applies to giving birth to a baby with a healthy brain and nervous system, and pregnant women should consume proper nutrients to support brain development. There are a number of known toxins, including lead, alcohol, mercury, tobacco, various insecticides, petrochemical products and some medicines that are harmful to fetal development. An important area of concern is our current environment and findings showing that food and water sources, and other common materials, can contain man-made chemicals.

A great deal of scientific attention is now being focused on the potential consequences of some of these chemicals on the bodily organs, including the brain, as well as possible mutagenic or harmful effects on the reproductive organs and human genes. There is a very real basis for concern that environmental toxins play a direct causative role or increase the risk for neurodevelopmental disorders, including ASDs. There is now much research underway to discover what types of chemicals present in the environment might be causatively implicated in ASDs.

S. Heller asks: What role do genetics play in autism and is there strong evidence suggesting a single gene or, specific group of genes, is causing the condition?

There is an ongoing debate about how much of the currently recognized prevalence of mild ASDs reflects an actual increase, involving both males and females, and how much is due to increased recognition of milder behavioral traits that were previously undetected or called something else. However, it is well-established that genes and heredity play an important causative role in the condition. This remains the case, even though it has recently been established that environmental causes have been underestimated. There are several hundred known gene abnormalities of differing types that are causally related to ASDs. More continue to be discovered all the time. A relatively small number of these gene abnormalities, if present in a developing child, incur great risk for the condition. Many others, some quite common, present as relatively low “risk factors” for ASDs.

When ASDs result in these individuals, it may be because numerous low-risk genes occurred together, or because a low-risk factor has combined with an environmental factor. There is an important distinction to be made between hereditary (familial genetic factors) that increase the risk of ASDs and non-hereditary genetic causes of the condition, which stem from “copying” mistakes that occur when the reproductive cells are being formed or duplicating in embryogenesis. The latter can result in a child being born with ASDs in a family that appears to have no special hereditary predisposition to the condition.

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Today is the final day of our Ask Stanford Med installment on autism. Questions related to treatment, diagnosis and research advancements can be submitted to Carl Feinstein, MD, director of the Stanford Autism Center at Packard Children’s Hospital, by either sending a tweet that includes the hashtag #AskSUMed or posting your question in the comments section of our previous entry. We’ll accept questions until 5 p.m. Pacific time.

And, as a reminder, Feinstein and others will be speaking next month at a day-long event geared towards parents, teachers, physicians and caregivers. The sixth annual Autism Spectrum Disorders Update will be held at the Stanford campus on June 1.

Among school-aged children in the United States an estimated one in 50 has been diagnosed with autism spectrum disorder, according to a recent survey (.pdf) from the Centers for Disease Control and Prevention. In addition to raising concerns among researchers and parents about why the number of cases has increased, the findings underscored the need to do more autism research and to provide support and services for families caring for autistic children.

To help parents and others in the local community better understand the growing prevalence of autism and to learn about treatments and research advancements, the Stanford Autism Center at Packard Children’s Hospital will host its sixth annual Autism Spectrum Disorders Update on June 1. The event offers an opportunity for exchange between parents, caregivers and physicians and provides an overview of the center’s clinical services and ongoing autism research at the School of Medicine.

In anticipation of the day-long symposium, we’ve asked Carl Feinstein, MD, director of the center, to respond to your questions about issues related to autism spectrum disorder and to highlight how research is transforming therapies for the condition.

At the Stanford Autism Center, Feinstein works with a multidisciplinary team to develop treatments and strategies for autism spectrum disorders. In providing care and support for individuals with autism and their families, Feinstein and colleagues identify ways of targeting the primary autism symptoms, while also paying attention to associated behavior problems that may hold a child back from school or community involvement or seriously disrupt family life.

Questions can be submitted to Feinstein by either sending a tweet that includes the hashtag #AskSUMed or posting your question in the comments section below. We’ll collect questions until Wednesday (May 15) at 5 PM Pacific Time.

When submitting questions, please abide by the following ground rules:

• Stay on topic
• Be respectful to the person answering your questions
• Be respectful to one another in submitting questions
• Do not monopolize the conversation or post the same question repeatedly
• Kindly ignore disrespectful or off topic comments
• Know that Twitter handles and/or names may be used in the responses

Feinstein will respond to a selection of the questions submitted, but not all of them, in a future entry on Scope.

Finally – and you may have already guessed this – an answer to any question submitted as part of this feature is meant to offer medical information, not medical advice. These answers are not a basis for any action or inaction, and they’re also not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and give you the appropriate care.

Previously: New public brain-scan database opens autism research frontiers, New autism treatment shows promising results in pilot study, Autism’s effect on family income, Study shows gene mutation in brain cell channel may cause autism-like syndrome, New imaging analysis reveals distinct features of the autistic brain and Research on autism is moving in the right direction
Photo by Wellcome Images

In a recent thought-provoking guest post on the NeuroTribes blog, autism activist Brenda Rothman discusses her personal journey coming to terms with her son’s diagnosis of autism and shares what she’s learned from him. In order to provide better support to autistic people and their families, she argues that society’s perspective of the neurological condition needs to shift from “awareness” to “acceptance:”

We need to challenge how autism is defined — as a set of behaviors and deficits – because this description leads us inexorably to “fixing” autistic people.  Autism is a way that the brain takes in, processes, and responds to information.  This way of processing results in variations in the way the world is experienced and the ways that learning, communication, and movement occur.  Autistic people develop skills on a different timetable or in a different order than expected.

But autism also comes with a set of strengths – a deep passion for interests, the ability to recognize visual, musical, social, or emotional patterns, and a strong individuality.  When we ignore autistic strengths, we ourselves become stuck on fixing autistic people, rather than building on their natural talents.

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We need to examine our response to autism.  When we start with the incorrect premise that autistic people don’t understand or misbehave, we end up with behavioral programs directed at training them to act in “normal” ways.  By recognizing that they already communicate and understand, we can identify the obstacles that make it difficult for them.  We can move from trying to fix the person to giving them the supports they need.  These supports include sensory-friendly environments, devices to assist communication, acceptance of moving around and stimming, and methods of learning that come most naturally to them. Creating supports like this are like building ramps for autistic people, instead of forcing them to climb stairs that exhaust and exclude them.

The full entry is worth a read.

Previously: New public brain-scan database opens autism research frontiers, New imaging analysis reveals distinct features of the autistic brain and Using music to improve communication skills in children with neurodevelopmental disorders

Scientists have a valuable new tool for studying autism: a public database of more than 1,000 brain scans. The scans, which were collected across the country via functional Magnetic Resonance Imaging (fMRI), are from individuals with autism and typical controls who range in age from 6 to 64 years old.

The database, called the Autism Brain Imaging Data Exchange, will alleviate a serious problem in autism research. MRI has already yielded insights into brain structure and function in autism, but many of the existing studies were limited by their small size. (It’s very difficult for any single researcher to collect enough brain images to run such a large study.)

To circumvent this problem, scientists at New York University’s Langone Medical Center and the Kennedy Krieger Institute led an effort to pool scans done in labs around the country. Stanford neuroscientist Vinod Menon, PhD, is among the researchers from more than 15 institutions who contributed brain scans to the new database. He has used MRI to study autism before, and when I spoke with him recently about the research possibilities opened by the new database, his excitement was palpable.

“Any researcher who is interested in conducting studies of brain networks in children and adults with autism will want to look very carefully at this data,” Menon told me, adding that the data set’s large age span will let researchers ask developmental questions that would otherwise be unanswerable. And having the database of scans sitting ready for analysis will make studies faster, less expensive and more replicable, he said.

Previously: New imaging analysis reveals distinct features of the autistic brain

Previous research has demonstrated the effectiveness of music therapy in treating children with Autism Spectrum Disorders (ASD).  A recent Atlantic article follows a student of a New York  therapeutic school for children with neurodevelopmental disorders and documents how adhering to music’s clearly defined structure helped the 13-year-old manage social interactions and other challenging life situations.

From the piece:

For the last four years, Jaden has been attending [Rebecca School] for music therapy – broadly defined as the clinical use of music for treatment of people with mental, physical or emotional issues. Jaden was born without a corpus callosum – the flat bundle of cells that connects the left and right sides of the brain, facilitating communication between the two hemispheres. He has minimal speaking skills, said Dr. Gil Tippy, [PsyD,] the Rebecca School’s clinical director, but it’s made up for by a penchant for music.

The term “music therapy” first appeared in The Columbia Magazine back in 1789, but it wasn’t until the 1940s that music therapy began to emerge as a clinical profession when hospitals used music to treat World War II soldiers suffering from shell shock. Using music as a therapeutic medium has been shown to facilitate motivation, communication skills and social interaction, and it improves attention spans among children with autism.

Instructors at Rebecca School, which also uses Developmental, Individual-Difference, Relationship-Based (DIR) therapy to reach children, may accompany students on another instrument, encouraging communication by matching pace and tone and even using the rhythm of a piece of music to influence energy states of the student; for example, slowing a beat to calm down a child. The skills acquired through music lessons can be applied elsewhere:

Individuals with ASD often find it challenging to maneuver social situations. That’s because they tend to focus on details, which restricts their ability to understand implicit social cues, said Andrew Gerber,[MD, PhD,] an assistant professor of clinical psychiatry in the Division of Child and Adolescent Psychiatry at Columbia Medical Center. That explains why music is often more appealing: the rules are better defined. “One of the real advantages of using music for a kid with autism is that it’s a chance to be able to teach him rules that are knowable,” said Gerber. “They can feel like they’ve mastered something. It makes sense to them.”

Jaden found his calling in percussion.

Previously: Autism therapies: It still comes down to parents
Photo by woodleywonderworks

An antioxidant supplement has shown early promise as a potential autism therapy, according to a small pilot trial from a Stanford research team. The study will be published June 1 in Biological Psychiatry.

From a press release I wrote to explain the new findings:

The antioxidant, called N-Acetylcysteine, or NAC, lowered irritability in children with autism as well as reducing the children’s repetitive behaviors. The researchers emphasized that the findings must be confirmed in a larger trial before NAC can be recommended for children with autism.

Irritability affects 60 to 70 percent of children with autism. “We’re not talking about mild things: This is throwing, kicking, hitting, the child needing to be restrained,” said Antonio Hardan, MD, the primary author on the new study. “It can affect learning, vocational activities and the child’s ability to participate in autism therapies.”

NAC has some important potential advantages over other autism therapies. Right now, irritability in autism is often treated with second-generation antipsychotics. These drugs produce a greater decrease in irritable behaviors than the Stanford team saw with NAC, but also have severe side effects, potentially causing weight gain, involuntary motor movements and metabolic syndrome, which can lead to diabetes.

In addition, no medications exist to treat repetitive behaviors and other “core features” of autism such as social deficits and language impairment. If the findings about NAC’s effect on repetitive behaviors are replicated in larger trials, NAC will be the first drug to treat one of the disorder’s core features.

Hardan’s team is now applying for funding for a large, multi-center trial of NAC. He told me:

One of the reasons I wanted to do this trial was that NAC is being used by community practitioners who focus on alternative, non-traditional therapies. But there is no strong scientific evidence to support these interventions. Somebody needs to look at them.

Previously: New imaging analysis reveals distinct features of the autistic brain

In an effort to automate early diagnosis of autism, researchers are testing a new system that combines Kinect motion sensors with computer-vision algorithms capable of detecting telltale signs of the behavioral disorder.

The experiment is underway at the University of Minnesota’s Institute of Child Development in Minneapolis. Inside the institute, five Kinect depth-sensing camera rigs installed in the nursery are used to monitor groups of roughly 10 children between the ages of 3 and 5 years old as they play. The New Scientist reports:

The cameras identify and track children based on their shape and the colour of the clothes they are wearing. The information is fed to three PCs, which run software that logs each child’s activity level – including how they move each of their limbs – and plots it against the room’s average. The system can flag up children who are hyperactive or unusually still – both possible markers for autism.

Medical staff can then decide whether the child requires closer attention from a specialist for a one-on-one diagnosis

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Ultimately, the team hopes to merge the Kinect work with another project it is working on. By studying video footage of children interacting with a psychiatrist, computer-vision algorithms learn to identify behavioural markers as designated on the Autism Observation Scale for Infants (.pdf). The system measures traits like a child’s ability to follow an object as it passes in front of the eyes, as well as noting certain mannerisms or postures that are classified as being early signs of a possible [autism spectrum disorder].

Researchers say that automating diagnosis of autism could result in children beginning speech therapy sooner and getting help learning social and communication skills, which can have a significant impact on treatment outcomes. Long-term, researchers hope to develop a video game for Kinect capable of testing a child as they played with a parent, meanwhile identifying any concerns.

Previously: Mobile app being developed to help people with autism and Could the iPad be an effective learning tool for children with autism?

Perhaps one of the biggest obstacles to research into autism and other psychiatric and neurological diseases is that scientists can’t get living brain cell samples from people with these conditions, for obvious reasons. Now neuroscientists at Stanford have figured out a solution to this dilemma, using a novel approach involving what are known as induced pluripotent stem cells, or iPS cells.

The new method involved taking skin cells from patients with Timothy syndrome (a rare genetic condition that includes autism as a symptom), converting the skin cells into stem cells and then converting those stem cells into neurons. By studying clumps of these neurons, the neuroscientists homed in on potential differences in autistic people’s brain cells. As described in a School of Medicine release:

In this study, the scientists suggest that the autism in Timothy syndrome patients is caused by a gene mutation that makes calcium channels in neuron membranes defective, interfering with how those neurons communicate and develop. The flow of calcium into neurons enables them to fire, and the way that the calcium flow is regulated is a pivotal factor in how our brains function.

The researchers also found brain cells grown from individuals with Timothy syndrome resulted in fewer of the kind of cells that connect both halves of the brain, as well as an overproduction of two of the brain’s chemical messengers, dopamine and norepinephrine. Furthermore, they found they could reverse these effects by chemically blocking the faulty channels.

The findings (subscription required) appear online in Nature Medicine. Researchers say the new technique to recreate how the neurons of individuals with Timothy syndrome develop in a lab setting could prove to be a powerful research tool by allowing scientists to study the disorder in human cells rather than mouse cells.

Previously: Stanford Magazine spotlights scientists’ efforts to untangle the root causes of autism, Joachim Hallmayer discusses new Autism Genome Project study, How better understanding Williams syndrome could advance autism research and Research on autism is moving in the right direction