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Autism, Pediatrics, Research, Stanford News

Girls with autism show behavior and brain differences compared to boys, Stanford study finds

Girls with autism show behavior and brain differences compared to boys, Stanford study finds

Boy&girlLast week, a new Stanford study answered one of the oldest questions in autism research: Does autism differ between boys and girls?

Yes, the study found. According to the results published in Molecular Autism, girls tend to have less severe manifestations of one core feature of autism, repetitive and restricted behavior, and they show brain-scan differences from boys that help explain the discrepancy.

Hints of a gender difference in autism extend all the way back to the first clinical report of the disorder, published in 1943, which described eight boys and three girls. 70 years after that report, boys are still more commonly diagnosed; among kids with high-functioning autism, the ratio of boys to girls is four to one. But questions about the nature of the gender split have persisted, as our press release on the work explains:

“We wanted to know which specific clinical manifestations of autism show significant gender differences, and whether patterns in the brain’s gray matter could explain behavioral differences,” said the study’s senior author, Vinod Menon, PhD, professor of psychiatry and behavioral sciences. Knowledge of the difference could help clinicians better recognize and treat autism in both sexes, he added. “Understanding this is really quite crucial clinically.”

Prior studies of the gender difference have typically been small and inconclusive. So the Stanford team took a new approach, using two large public databases that capture information from patients all over the country. This allowed them to study almost 800 children who fit a fairly narrow set of criteria: age 7 to 13, evaluated by standard tests for autistic behavior, and with an IQ above 70.

Girls had lower (more normal) scores than boys on a standard evaluation of repetitive and restricted behavior, which includes preoccupation with narrow interests, inflexibility about routines and repetitive motions such as hand-flapping, the study found. Girls and boys did not differ on measures of autism’s other core features, which are social and communication deficits.

MRI brain scans on a subset of the children showed different grey-matter patterns between boys and girls in the motor cortex, supplementary motor area and part of the cerebellum. These areas help the brain plan and carry out motor functions, which the researchers said was noteworthy because many repetitive behaviors have a motor component.

“The discovery of gender differences in both behavioral and brain measures suggests that clinicians may want to focus diagnosis and treatments for autistic girls differently than boys,” [lead author Kaustubh] Supekar,PhD, added.

Previously: A new insight into the brain chemistry of autism, Unlocking autism’s secrets: Stanford researchers point fingers at a brain cell dark horse and Parents can learn autism therapy in groups to improve kids’ verbal skills, Stanford study shows
Photo by Barbara Abate

Autism, In the News, Neuroscience

A tribute to Oliver Sacks, from a science writer

A tribute to Oliver Sacks, from a science writer

Library-stacksThe news this weekend of neurologist and writer Oliver Sacks’ death brought back a crystalline memory of myself at 18, searching through the library stacks for a copy of his 1973 book, Awakenings. I needed it because the brains did not show up.

An explanation is in order: The spring semester of my college-freshman biology class included a six-week lab elective. Of a few dozen elective options, I picked “The Brain” because the descriptive blurb said each student would get to dissect a sheep brain. I was a bit grossed out by the idea of a sheep brain in front of me on a tray, but my curiosity outweighed my squeamishness. I intensely wanted to examine a real brain.

However, on the first day of The Brain, our teaching assistant broke the bad news: No brains. The room moaned in dismay.

“I know,” he said. “I’m really sorry. To make it up to you, I’m going to let you each do a short report on anything you want, as long as it has some relationship to the brain.”

I had seen the movie version of Awakenings a few years earlier (with Robin Williams playing Sacks) and remembered my mom saying that there was a book, too, but that she had heard it was clinical and dull. Well, I thought, clinical isn’t so bad, and I can stomach dull if it lets me present a book report about a weird brain disease. The TA approved my topic, and off I went to the university’s biomedical library, where the long, dim, badly ventilated staircases gave me attacks of claustrophobia.

Up the dreaded stairs, through the overheated, papery-smelling stacks to the book itself: A library edition, small and lightweight in my hands, bound in an ugly turquoise cover. A book that, once I opened it, I could not put down. Yes, the writing was clinical – there were medical words, and patients were disguised behind names like “Miriam H.” – but dull? No. An adventure in the brain: patients who had been frozen for decades with post-encephalitic parkinsonian syndrome coming to life again when Sacks gave them a drug, only to slowly sink back into their freeze as the drug stopped working for them.

The main thing I remember thinking is: Eeeeeeee! I want to write stories like this! It did not seem like a dream that had any hope of being realized, since I had no intention of becoming a neurologist. I let the impulse go, prepared my Brain report (a success), and subsequently read many more of Sacks’ books – with great pleasure.

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Autism, Behavioral Science, Medical Apps, Nutrition, Stanford News, Technology

Stanford grad students design new tools for learning about nutrition, feelings

Stanford grad students design new tools for learning about nutrition, feelings

2789442655_1f5c33ac51_zMushrooms and tomatoes, veggies that are often reviled by preschoolers, star in a new app designed by a Stanford graduate student that aims to involve children in preparing, and eating, healthy meals.

“Children are more likely to try food that they’ve helped cook,” explained Ashley Moulton, a graduate student in the School of Education’s Learning, Design and Technology Program, in a recent Stanford News story.

Moulton’s iPad app, Nomster Chef, is one of several student projects featured in the article and accompanying video:

Before cooking, children receive an educational video about a food they’ll be working with – for example, a video on how mushrooms grow. The app also incorporates food information in the recipe steps, like the fact that tomatoes are actually a fruit.

After user-testing the app prototype, “I heard from parents that they noticed differences in how their kids are eating,” Moulton said. The app also kept kids engaged throughout the cooking process.

For her project, fellow student Karen Wang developed an iPad app called FeelingTalk that helps children with autism interpret facial expressions:

…[I]n the first level of FeelingTalk, kids choose the one face that’s different (a sad face) from the three happy faces on the screen. The app will then label the different face “sad.”

“My app will be utilizing learning mechanics that directly work with the autistic brain to help them work on something that they’re having difficulty with,” Wang said. “By leveraging something they’re good at, we’re going to teach them to get comfortable looking at people’s faces, examining the key features, and eventually understanding emotions.”

Moulton, Wang and other students will present their work this afternoon at the LDT Expo at the Stanford Graduate School of Education.

Previously: A look at the MyHeart Counts app and the potential of mobile technologies to improve human health and No bribery necessary: Children eat more vegetables when they understand how food affects their bodies
Photo by Peter Weemeeuw

Autism, Behavioral Science, Neuroscience, Pediatrics, Research, Stanford News

A new insight into the brain chemistry of autism

A new insight into the brain chemistry of autism

TrueHugFor several years now, scientists have been testing the hypothesis that one particular hormone, oxytocin, plays a role in autism. It seems logical: After all, this molecule nicknamed the “love hormone” promotes bonding between romantic partners and is one of the main signals involved in childbirth, breastfeeding and helping new mothers form strong bonds with their babies. And social-interaction difficulties are a known characteristic of autism, a developmental disorder that affects one in every 68 kids.

But in the flurry of interest around oxytocin, a related signaling molecule has been largely overlooked. Called vasopressin, it’s structurally very similar to oxytocin. Both are small proteins made of nine amino acids each, and the amino-acid sequence is identical at seven of the nine spots in the two hormones. Vasopressin is best known for its role in regulating blood pressure, but it also has social roles, which have mostly been studied in rodents.

Noting the dearth of autism-vasopressin research, a Stanford team decided to study vasopressin levels and social behavior in children diagnosed with autism and controls who had not been diagnosed with autism. Our press release about their study, which was published today in PLOS ONE, explains:

The research team found a correlation between low levels of vasopressin, a hormone involved in social behavior, and the inability of autistic children to understand that other people’s thoughts and motivations can differ from their own. …

“Autistic children who had the lowest vasopressin levels in their blood also had the greatest social impairment,” said the study’s senior author, Karen Parker, PhD, associate professor of psychiatry and behavioral sciences.

Parker and her colleagues examined “theory of mind,” the ability to deduce that others have a mind of their own – and that they may perceive the world differently than you do. It’s an important underpinning to forming empathetic relationships with other people. In kids with autism, the lower their vasopressin levels, the worse their scores on a test of theory of mind, the study found. Children without autism did not show this link; they all had pretty good theory of mind scores, whether their vasopressin levels were low or high.

It’s worth adding that low vasopressin level did not diagnose whether a child had autism; the hormone’s levels ranged from low to high in both groups of children. So autism is not simply a state of vasopressin deficiency. However, the researchers are interested in whether giving vasopressin might help relieve autism symptoms and are now carrying out a clinical trial to test its effects.

The work also provides an interesting complement to oxytocin findings published by the same team last year. In the oxytocin study, the scientists found that children with autism could have low, medium or high oxytocin levels, just like other children. However, oxytocin levels were linked to social ability in all children, not just those with autism.

Based on the new findings, it’s possible, Parker told me, that vasopressin is uniquely important for children with autism. She’s eager to expand her work in this overlooked corner of brain-chemistry research.

Previously: Stanford research clarifies biology of oxytocin in autism, “Love hormone” may mediate wider range of relationships than previously thought and Volunteers sought for autism drug study
Artwork by Dimka

Autism, Mental Health, Neuroscience, Research, Science, Stanford News, Stem Cells

Brain cell spheres in a lab dish mimic human cortex, Stanford study says

Brain cell spheres in a lab dish mimic human cortex, Stanford study says


Mental disorders like autism and schizophrenia are notoriously difficult to study at the molecular level. Understandably, people are reluctant to donate pieces of living brain for study, and postmortem tissue lets researchers see the structure, but not the function, of the cells.

Now researchers in the laboratories of psychiatrist Sergiu Pasca, MD, and neurobiologist Ben Barres, MD, PhD, have found a way to make balls of cells that mimic the activity of the human cortex. They use a person’s skin cells, so the resulting “human cortical spheroid” has the same genetic composition as the donor. The research was published in Nature Methods yesterday.

According to our release:

Previous attempts to create patient-specific neural tissue for study have either generated two-dimensional colonies of immature neurons that do not create functional synapses, or required an external matrix on which to grow the cells in a series of laborious and technically difficult steps.

In contrast, the researchers found they were able to easily make hundreds of what they’ve termed “human cortical spheroids” using a single human skin sample. These spheroids grow to be as large as 5 millimeters in diameter and can be maintained in the laboratory for nine months or more. They exhibit complex neural network activity and can be studied with techniques well-honed in animal models.

The researchers, which include neonatology fellow Anca Pasca, MD, and graduate student Steven Sloan, hope to use the technique to help understand how the human brain develops, and what sometimes goes wrong. As described by Barres:

The power and promise of this new method is extraordinary. For instance, for developmental brain disorders, one could take skin cells from any patient and literally replay the development of their brain in a culture dish to figure out exactly what step of development went awry — and how it might be corrected.

The research is starting to garner attention, including this nice article from Wired yesterday. Pasca’s eager to note, however, that he’s not working to create entire brains, which would be ethically and technically challenging, to say the least. But simply generating even a few of the cell types in the cortex will give researchers a much larger canvas with which to study some devastating conditions. As Pasca notes in our release:

I am a physician by training. We are often very limited in the therapeutic options we can offer patients with mental disorders. The ability to investigate in a dish neuronal and glial function, as well as network activity, starting from patient’s own cells, has the potential to bring novel insights into psychiatric disorders and their treatment.

Previously: More than just glue, glial cells challenge neuron’s top slot and Star-shaped cells nab new starring role in sculpting brain circuits
Photo of spheroid cross-section by Anca Pasca

Autism, Ethics, Genetics, Medicine and Society, Patient Care

Genetic testing, autism, and “fixing” the pathological body

Genetic testing, autism, and "fixing" the pathological body

2678541254_029f25704b_zHow do we know what is pathological, versus what is normal? It seems obvious until you start thinking philosophically, which was the goal of a panel hosted last week by the Science and Justice Working Group at University of California, Santa Cruz. The event was titled “‘Fixing’ the Pathological Body,” a pun on how fixing can mean both repairing and immobilizing.

An anthropologist, a philosopher, and a geneticist discussed how simple, everyday practices like using particular words or certain tests define a line between pathology and normalcy. That line has a huge impact on our experience as humans.

Matthew Wolfmeyer, PhD, professor of anthropology at UCSC, used the term “multibiologism” to indicate that pathology can be seen as a form of human variation. There are three kinds of bodies, he says: those that need no intervention of social, legal, or medical support to enable a livable life, those that do need such intervention (such as a quadriplegic or someone with severe Alzheimer’s), and those that could have such intervention (anyone from hyperactive kids or insomniacs to those with PTSD or arthritis). American society currently divides this spectrum such that the “no intervention” category is becoming empty and the “could have intervention” category is growing by leaps and bounds. Despite what he calls our “cure ideology” from our Judeo-Christian heritage, the pathologies we recognize are increasingly incurable, whether it be gluten sensitivity or chronic cancer, and must be treated with ongoing therapies.

Kelly Ormond, MS, professor of genetics at Stanford, provides genetic counseling and helps people think about these issues every day. She helps expectant parents face the grueling task of deciding what it means to have a baby who might be labeled disabled, pathological, or normal — how would such a child fit into their life, and are they able and willing to accommodate that? Do they even want the information that genetic tests can offer? When counseling parents, Ormond tries to emphasize the lived experience of a condition instead of its medical aspects. Medical information tends to categorize and stir up preconceived notions, but in everyday life the significance of such designations is more fluid, she said.

Janette Dinishak, PhD, professor of philosophy at UCSC, studies autism. She wants to reframe society’s understanding of people with autism such that those without autism are the ones who are limited.

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Autism, Genetics, Research, Stanford News

Unlocking autism’s secrets: Stanford researchers point fingers at a brain cell dark horse

Unlocking autism’s secrets: Stanford researchers point fingers at a brain cell dark horse

Snyder smilingGeneticist Michael Snyder, PhD, has a thing for ‘omes.’ He’s studied genomes, transcriptomes, proteomes and microbiomes. Each term represents looking at something (DNA, RNA, proteins or microorganisms on a grand scale, throughout an entire organism). Most recently he’s been known for combining omics information to generate a dynamic picture of his own changing health over time (he termed the analysis a “integrative personal omics profile, or iPOP, but really, the siren call of “the Snyder-ome” is almost too great to resist).

Now he and postdoctoral scholar Jingjing Li, PhD, have turned their attention to the human “interactome,” a database that includes information about more than 69,000 protein interactions. They’ve used sophisticated algorithms to identify who in the brain is playing nicely with whom, and identified a particular group that seems to play an important role in the development of autism in a part of the brain called the corpus callosum. Importantly, the analysis points a finger at a new cell type in the brain — the oligodendrocytes. These serve as kind of a pit crew for the neurons, coating them in an insulating material to keep electrical signals between cells running smoothly. They’ve published their work today in Molecular Systems Biology.

As Snyder explained in our release:

This is our first glimpse of autism’s underlying biological framework, and it implicates a cell type and region of the brain that have not been extensively studied in this disease. Until now, we’ve suspected that autism could be the result of defects in the neurons themselves. Now it appears that the oligodendrocytes can contribute to the problem by inhibiting neuronal signaling through poor cellular differentiation and myelination.

Snyder, who also directs Stanford’s Center for Genomics and Personalized Medicine, and Li hope that the finding will allow researchers to broaden their net to the corpus callosum, which helps the two halves of the brain communicate with one another. As psychiatrist and study co-author, Joachim Hallmayer, MD, commented:

Autism is an extremely heterogeneous disease. Many genes have been implicated, but environment also plays a role. This study suggests a possible way to subdivide patients into smaller, more homogenous populations based on which genes are mutated. Some of these may be very easy to treat, based on their mechanism, while others may be much more difficult. For those in this category, it’s possible we could one day find a way to train or improve the connection between the brain’s hemispheres.

It will be fascinating to see where this research goes next. In the meantime, here’s hoping the New Year-ome treats you and yours well!

Previously: New imaging analysis reveals distinct features of the autistic brain, Omics’ profiling coming soon to a doctor’s office near you? and A conversation with autism activist and animal behavior expert Temple Grandin
Photo of Snyder by Steve Fisch

Autism, Behavioral Science, Events, Stanford News

Thinking in pictures: Stanford hosts Temple Grandin

Thinking in pictures: Stanford hosts Temple Grandin

Grandin Temple - smallEarlier this week, I got to hear a presentation by Colorado State University animal behavior expert Temple Grandin, PhD, who is widely known not just for her extensive work to enhance animal welfare, but also because she is one of the world’s most prominent individuals with autism. Like many others, I first became familiar with Grandin’s work through Oliver Sacks’ 1995 book, An Anthropologist on Mars. (The title came from Grandin’s description of how she feels when trying to decode the subtleties of social interactions.) Since I first read Sacks’ book, I’ve written frequently about autism research and treatment, and I’ve gotten some sense of how phenomenally important Grandin is to the autism community. So it was quite a thrill to be sitting just a few feet from her as she spoke to an overflow crowd at the School of Medicine.

Grandin’s talk focused on understanding animal behavior and reducing animals’ stress, but she interwove descriptions of her research with comments on how living with autism has influenced her work – and, indeed, how it influences the world around us. “A little bit of autism gives you Silicon Valley,” she quipped in the introduction to her talk. Although her subject was animals’ stress, at the heart, she was explaining different ways of thinking: in words or in pictures.

Animals think in pictures, especially when it comes to determining which elements of their environment are stressful or frightening, Grandin said: “Animals are all about sensory detail, little bits of detail we tend not to notice.” At one point in the talk, she showed a photo of a cow bending forward to investigate a spot of sunlight on the floor of the room where it was about to have a veterinary exam. To a human, this spot would likely seem insignificant, but to the cow, it is a foreign object that needs to be approached with caution.

“Novelty is a strong stressor for animals,” Grandin said, adding that if something visually new is forced in an animal’s face, it’s scary. The cow in the photo needs a few minutes to sniff the sun spot and figure out that it’s harmless; a human trying to force the situation will soon have a frightened, resistant animal to handle. Humans also have to keep in mind that our word-oriented brains may not categorize “novelty” in the same way that an animal does. For instance, an animal that has become accustomed to the sight of a blue-and-white umbrella may still be frightened by an orange tarp, Grandin said. To people, they’re both rain protection, but to a horse or cow, “It’s a different picture!”

Like many children with autism, Grandin began speaking later than most kids, and she still thinks in images more intuitively than words. “I see movies in my imagination, and this helped me understand animals,” she said. She likened her memory to Google Images, explaining that for her, a particular word will pull up many associated images, categorized by type. Her designs for meat-processing plants, now in use in half of the meat-processing facilities in North America, rely on her ability to mentally take a “cattle’s-eye view” of each step in the animal’s journey before slaughter, playing out a movie in her head that shows her where animals could be forced to encounter new things that might frighten them.

As well as describing her own work, Grandin advocated for broader acceptance of different kinds of thinkers, both with and without autism. People may think predominantly in pictures, or in patterns (that’s the math whizzes among us), or in words, she said, and we need educational and employment systems that can nurture and benefit from each of these ways of thinking. “There is too much emphasis on deficits [of children with autism], and not enough on building their strengths,” she said.

Grandin’s complete talk, which was hosted by the Department of Comparative Medicine, will soon be available on the department’s news website.

Previously: A conversation with autism activist and animal behavior expert Temple Grandin, Growing up with an autistic sibling: “My sister has a little cup” and Finding of reduced brain flexibility adds to Stanford research on how the autistic brain is organized
Photo by Rosalie Winard

Autism, Events, Stanford News

A conversation with autism activist and animal behavior expert Temple Grandin

A conversation with autism activist and animal behavior expert Temple Grandin

Grandin Temple - 560

In the inspiring film, “Temple Grandin,” we learn the remarkable story of a woman born with autism who, as a young child, communicates through screaming and humming, and is given to fist-pumping outbursts of frustration. But Grandin, played brilliantly in the film by Claire Danes, has a rare affinity with animals and a keen sense of their needs. She ultimately becomes a renowned expert in animal behavior, a university professor and a consultant to major U.S. companies.

Grandin, PhD, one of the world’s most famous people with autism, will visit Stanford’s medical school next Wednesday to deliver a talk entitled, “Animals Make us Human.” In anticipation of her presentation, we asked her to answer five questions about the link between autism and animals. Her answers – like this one – offer a window into the world of autism, while providing a sense of Grandin’s character and thought process:

Animal cognition has similarities to autism cognition. Animals are very aware of small, sensory details in the environment. People on the autism spectrum excel at work involving details. SAP, a large computer company, is hiring people on the mild end of the autism spectrum to debug and correct computer programs.

Concepts are formed from specific examples. To train a dog to always obey the “sit” command, it must be taught in many different locations. If all the dog’s training is done in the living room, the dog may only obey the commands in the living room. To teach a child with autism about road safety, he needs to be taught in many different locations. These similarities between animals and autism apply only to cognition. They do not apply to the emotions. Animals are highly social and emotional creatures.

Her presentation begins at noon in the Clark Center on the medical school campus and will be followed by a book signing at the bookstore at the Li Ka Shing Center for Learning and Knowledge. The talk, sponsored by Stanford’s Department of Comparative Medicine, is free and open to the public. If you’re local and able to attend, I would get there early, as I believe this is going to be one very popular event.

Photo by Rosalie Winard

Autism, Behavioral Science, Parenting, Pediatrics, Research, Stanford News

Study validates oxytocin levels in blood and suggests oxytocin may be a biomarker of anxiety

Study validates oxytocin levels in blood and suggests oxytocin may be a biomarker of anxiety

Karen Parker Oxytocin, sometimes dubbed “the love hormone,” can be tricky to study in humans. To conduct research on the connection between oxytocin and emotion, scientists want to assess the hormone’s levels in the brain. But sampling cerebrospinal fluid, the liquid bathing the brain, requires an invasive technique called a lumbar puncture. Measuring blood oxytocin is much easier, but some researchers have questioned whether blood oxytocin levels truly reflect what’s happening in the brain.

A new Stanford study simplifies the problem: It is the first research in children, and some of the first in any age group of humans, to indicate that blood and CSF oxytocin levels track together. The research also found a correlation between low-oxytocin and high-anxiety levels in children, adding to findings from animal studies and adult humans that have documented this oxytocin-anxiety link. The paper appears today in Molecular Psychiatry.

The findings raise the possibility that oxytocin could be considered as a therapeutic target across a variety of psychiatric disorders

The researchers recruited 27 volunteers from among a group of patients who needed lumbar puncture for medical reasons. The volunteers agreed to have oxytocin levels measured in their blood and CSF, and the parents of 10 children in the study answered questions about their children’s anxiety levels. From our press releaseabout the research:

“So many psychiatric disorders involve disruptions to social functioning,” said the study’s senior author, Karen Parker, PhD, assistant professor of psychiatry and behavioral sciences. “This study helps scientifically validate the use of measuring oxytocin in the blood, and suggests that oxytocin may be a biomarker of anxiety. It raises the possibility that oxytocin could be considered as a therapeutic target across a variety of psychiatric disorders.”

Parker’s team is now conducting studies of possible therapeutic uses of oxytocin in children with autism. They recently published a paper demonstrating that autism is not a disease of oxytocin deficiency per se; instead, oxytocin levels in kids with autism fall across a broad range. The findings hint at a future in which patients’ oxytocin levels could be used to guide treatment for autism or other psychiatric or developmental disorders. As Dean Carson, PhD, the lead author of the new study, explained:

“Our belief is that there are oxytocin responders and nonresponders,” Carson said, adding that the team is now testing this hypothesis.

…“Being able to have objective measures of psychiatric illness really will enhance early diagnosis and measures of treatment outcomes,” Carson said.

Previously: Stanford research clarifies biology of oxytocin in autism, “Love hormone” may mediate wider range of relationships than previously thought and Study shows oxytocin may boost happiness among women
Photo of Karen Parker by Norbert von der Groeben

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