Wednesday, January 27, 2016

CHOP Researchers Identify Gene That Plays Important Role in Autism & Other Neuropsychiatric Conditions

A team of researchers led by Tara Wenger, PhD of The Children's Hospital of Philadelphia's Center for Autism Research (CAR) have found that genetic mutations in a specific family of genes – the “metabotropic glutamate receptors” (mGluRs) – play a significant role in a person’s risk for autism spectrum disorder (ASD). One mGluR gene in particular- RANBP1- was the focus of a study published this month in the Nature journal Scientific Reports. The mGluR gene network typically contains two copies of RANBP1; however, in children who were missing one of those RANBP1 genes, the risk of autism increased dramatically.

Previous studies have shown that RANBP1 contributes to “syndromic autism”- a form of ASD caused by genetic mutations that lead to complex medical problems. Syndromic ASD, which includes 22q11.2 Deletion Syndrome, Fragile X Syndrome, and Tuberous Sclerosis, accounts for about 20% of all ASD cases and  are frequently more severe forms of ASD.

The new CAR
study confirms the important role of mGluR genes in other neuropsychiatric conditions, such as attention-deficit hyperactivity disorder (ADHD), in addition to autism. Moreover, this mGluR family of genes contains hints about how several well-known environmental factors may cause ASD, including prenatal exposure to thalidomide. The scientists say these findings pave the way for developing precision treatments targeted to those who carry this genetic variation.

“This is another step in of a series of genetic findings that shine a spotlight on select aspects of early neurodevelopment that contribute most to ASD,” said Robert Schultz, PhD, Director of the CAR. “At CHOP we are extremely fortunate to be able to convene the resources and expertise of the
Center for Applied Genomics (CAG), the 22q and You Center, and CAR in order to examine complex genetic questions – spanning multiple diagnoses- in order to tease out important interactions among genetic and environmental factors that increase a child’s risk of developing ASD, and in turn develop targeted treatments. There are only a few places in the world positioned to do this type of research.”

For this study, scientists analyzed DNA from more than 500 children with ASD. They searched for copy number variations (CNVs) within the mGluR gene network, since previous studies have shown that CNVs within this mGluR “gene family” occur more frequently in children with ASD than in other children. The research team discovered that children with ASD who also had CNVs within the mGluR network were far more likely to have the syndromic type of ASD, compared to those without CNVs in mGluR.

The study team also compared the ASD cohort to a separate set of 75 children with 22q11.2 deletion syndrome, 25 of whom also had ASD. All 75 were already missing RMBP1, because that gene is contained in the deleted region of their chromosome.  But if they had a “second hit”—either a deletion or a duplication of another mGluR gene outside that region—they were much more likely to have autism than children with the deletion syndrome who didn’t have that second hit.
Combining these findings, the research team concluded the RANBP1 gene is a significant genetic factor in some forms of ASD, and the greater number of mGluR genes affected, the greater the chances of the person developing ASD. “The mGluR variants we identified may be important in identifying those patients who are most likely to respond to new treatments,” said Hakon Hakonarson, MD, PhD, Director of the Center for Applied Genomics at CHOP. “As such, this could be the basis for one of the first examples of a precision medicine focus in drug development for complex disease.”
This study, entitled "The Role of mGluR CopyNumber Variation in Genetic and Environmental Forms of Syndromic AutismSpectrum Disorder”, was published January 19th in Scientific Reports. The study was led by Tara Wenger, MD, PhD of CHOP’s Center for Autism Research and Hakon Hakonarson, MD, PhD, director of CHOP’s Center for Applied Genomics. Co-authors included Robert Schultz,PhD, director of CHOP’s Center for Autism Research and Donna McDonald-McGinn, MS, CGC, program director of CHOP’s 22q and You Center. Find more information about these research findings in the accompanying press release. 

Switching Lenses: A Shift in Perspective Led Researchers to Unexpected Results About Face-Processing in ASD

Humanity seems to be “hard-wired” to pay attention to faces and facial expressions. Zeroing in on faces (rather than other body parts or objects) and being able to differentiate between people’s identities or expressions is one of the first skills developed during infancy; and differences in social attention appear to be one of the earliest observable signs of autism.
Because reduced attention to and interest in social information is a prevalent symptom of ASD, many studies have focused on comparing two groups - those on the spectrum vs. those with typical development - to search for differences in how they prioritize faces compared with other objects in the environment. However, no one had studied individual differences along the continuum of “face expertise”, without taking diagnostic labels into account. A group of CAR scientists led by Julia Parish-Morris, PhD, and Coralie Chevallier, PhD (now at INSERM), believed that ignoring diagnostic categories in favor of a more “dimensional approach” might improve our understanding of how humans develop their facial recognition skills and might also shed light on how differences in attentional biases or motivation to look at faces might influence the development of social skills.
For their study, the researchers enrolled 110 children between the ages of 6 and 17 (50 typically developing and 60 with ASD). The children participated in a series of scientifically validated tests, including Let’s Face It! - a computer game-based intervention designed help teach facial processing skills- to assess their ability to recognize both a person’s identity and perceive differences in facial expressions. They also watched short videos showing faces and objects, while their eye movements were tracked to measure gaze and attention. The team assessed each child’s behavior and social using the Social Communication Questionnaire (SCQ).
“We were surprised to find that, overall, children with ASD and their typically developing peers spent a similar amount of time looking at faces and objects,” explained Dr. Parish-Morris.
Interestingly, children who paid more attention to facial information were better able to differentiate between face identities and facial expressions in the Let’s Face it game, and so did children who performed better on the SCQ.

According to Dr. Parish-Morris, “The connection between attention to faces and face processing skill held regardless of whether or not the participant had autism. This suggests that face processing is truly dimensional and linked to underlying differences in social attention or motivation.” The Social Motivation Theory of autism suggests that while these differences might start small, they could have a snowball effect on face processing skill over developmental time.

Using a dimensional approach to assess social processing in autism is gaining favor across multiple areas of mental health research, and is consistent with a growing trend to think of ASD in terms of neurodiversity. Just as autism displays itself across a wide spectrum of symptoms and characteristics, it can be helpful for researchers to take a spectrum-approach as well, rather than adhering to strict diagnostic categories at the outset.

Shifting the lens through which we study ASD creates the potential for new pathways to understanding the variability that makes the diagnosis so challenging. Parish-Morris and her colleagues are interested in further exploring  the relationship between social interest, social motivation, and a person's  ability to identify and interpret faces as a potential area of interest for developing effective skill-building tools.

Friday, December 11, 2015

New Findings related to Attention and Gaze Give Us Clues to Differences in Social Development for Individuals on the Autism Spectrum

Difficulty interpreting social information is one of the defining characteristics of autism spectrum disorders (ASD), but  there is still a lot we don't understand about the underlying causes of some of these social differences.  A key aim of our research at CAR is to advance our understanding about the origins of difficulty with processing social information that is so common in ASD. This knowledge will help us devise better therapies.

There are four key areas of social development that are commonly disrupted by autism which, when taken together, describe much of what it means to have ASD. They include (1) theory of mind, or the ability to understand the thoughts, beliefs, or intentions of others (2) joint attention, or the inclination to pay attention to the same object of interest as someone else, as it relates to speech development; (3) social perception, or the ability to recognize facial expressions or speech inflections; and (4) social attention, or the tendency to prioritize important social information, such as an angry or distressed facial expression, over non-social information, such as pictures on a wall or furniture in a room.

In this the next couple of blog posts, we take you on a deeper dive into a group of CAR studies that are beginning to unlock some answers as to how social attention develops in autism.

"Why on earth would I want to do that?": The Basics of Social Motivation in Autism Spectrum Disorders

New CAR Research: Attention and Gaze Hold Clues to Social Development in Autism


Holly Robinson Peete Visits CAR

We were excited to have a visit last month from Philadelphia's own Holly Robinson Peete during a trip back to her hometown, where she was being honored for her efforts in support of autism awareness. Holly and her husband, former Philadelphia Eagles QB Rodney Peete, created the HollyRod Foundation to support families living with ASD and with Parkinson's disease, both of which affect their family directly.

The HollyRod Foundation made a very generous donation of Puzzlepiece tablets and toys for CAR's waiting room, along with several copies of "My Brother Charlie", a book Holly co-wrote with her daughter to help children understand classmates and loved ones with ASD. The book was inspired by Holly's son, RJ (now 19 years old) who was diagnosed with ASD as a child.

Here are a few great shots from our visit!

Holly Robinson Peete checks out our CAR logo- which was originally a quick sketch made by a boy with ASD while visiting the center!

Holly poses with 11-year-old Corinne, who is showing off her signed copy of  "My Brother Charlie".

Testing out the PuzzlePiece tablets!

CAR researcher Eli Kim explains one of our research studies aimed at understanding common physical behaviors associated with autism spectrum disorders.


CAR Research: Attention and Gaze Hold Clues to Social Development in Autism

Children with autism spectrum disorders (ASD) focus their attention on social information differently from their neurotypical peers, and this gives us a glimpse into social development as they mature. Improving our understanding of how these differences work may provide clues to developing treatments and interventions to ease some of the social symptoms of autism spectrum disorders (ASD).

CAR psychologist
Benjamin Yerys, PhD, studies attention, impulsivity, and distractibility in ASD, as well as in ADHD and anxiety- ASD’s frequent companions. A pair of his studies contribute to our understanding of how children with ASD prioritize and respond to social information in their environment.

“Now you see it….”: The Attentional Blink Effect in Autism

The first study tested what’s known as the “attentional blink effect” in 8-14 year-old children diagnosed with an autism spectrum disorder (ASD) vs. typically developing peers. Attentional blink refers to a gap in the brain’s ability to detect visual information when it appears in rapid succession. (Think about trying to identify a single card as someone shuffles the deck.) This is a result of a brief “overload” in the brain’s capacity to process information. Essentially, the brain needs a brief moment of unawareness, equivalent to a “blink”, to recover its ability to pay attention to new visual information. This idea is best explained with an example. Imagine you’re shown a series of images of different shapes on a screen, each appearing for a fraction of a second. You’re told to look for a triangle, and that a heart shape may also appear in the series. It’s highly likely that you’ll notice the triangle, but will miss the heart shape while your brain recovers its ability to focus on the images.

The exception to this rule is when the visual information carries emotional weight. For example, if an angry face is among the images shown after the picture of the triangle, you will be more likely to notice it, meaning the “blink” effect is overridden by a strong emotional stimulus. 

When this study was previously conducted in adults with ASD, those on the autism spectrum were less likely than neurotypical adults to pick up emotionally-charged images. However, when Dr. Yerys tried this same test with children using photos of dogs, neutral facial expressions, and angry facial expressions, the children diagnosed with ASD performed just as well as – or slightly better than - their typically developing peers. This was a surprising finding because the amygdala area of the brain is very important for processing emotional information quickly, and this area of the brain develops atypically in ASD starting in toddlerhood. This means that in children with ASD, the ability to prioritize social-emotional information is somehow preserved. Further research is needed to determine if this would also hold true for children more severely affected by ASD.

“Although we were initially surprised, this finding does make developmental sense,” said Dr. Yerys. “In general, adolescents and pre-adolescents tend to have a heightened response to emotional information. It is important that emotionally-charged information may grab attention to the same degree for kids on the spectrum as those considered to be typically developing, because it means that this age range may present a window of opportunity for possible interventions.”

“Inhibition of Re…what?” Visual Search for Social Information Differs for Children on the Autism Spectrum

In a related study published in November, Dr. Yerys and his colleagues explored social attention in 8-17 year-old children by looking at how children shift their attention to search their environment, instead of responding by reflex to the environment as we saw in the attentional blink study. When children (or adults) search their environment, the brain tends to favor searching new locations instead of going to old locations. For example, if you lost your keys then you may be more interested to look for them in your desk rather than searching your pocket a second time. This process is called “
inhibition of return” (IOR).

In neurotypical development, people tend to automatically skew their attention toward social information (facial expressions, body language, emotional cues), as opposed to objects in their environment which carry no social significance (an electrical outlet, a tree, a particular toy).

Earlier studies have established that photos of angry or upset faces hold the attention of neurotypical individuals longer than smiling or neutral faces (because anger and worry indicate a potential threat). The threat-related faces override or delay the brain process that would usually cue the brain to move on and scan for new visual information. Until now, no studies have carefully examined whether this “override” effect would also hold true for people with ASD.

To test whether children with ASD would prioritize socially or emotionally charged information in a similar way, children in this study were given a series of tasks to complete on a laptop. They were instructed to respond as quickly as possible to various combinations of non-social symbols and sets of photos showing either neutral or angry facial expressions.

Dr. Yerys and his team found that young people with ASD were less accurate in their responses; they also had longer response times when compared with their typically developing peers. Children who had the most severe ASD symptoms were also the slowest to shift their attention. This is the first large study to show that this visual attention mechanism (IOR) is disrupted in children with ASD, and that this impaired attention is directly related to some of the core social symptoms of ASD.

The study also ruled out the possibility that this difference in attention is related to ADHD or anxiety symptoms, which are common in children diagnosed with ASD. The study results support the overarching hypothesis that problems with how children prioritize social or emotional information in visual attention is associated with more severe social impairments.

Putting it all together
Taken together, the “attentional blink” study and the “inhibition of return” studies indicate that emotional information captured the attention of adolescent and pre-adolescent children with ASD to the same degree as it did for their typically developing peers, when information was being gathered from a single point in space. However, adding the task of scanning a given area for information and then determining its social meaning may prove more difficult for children with ASD.

It also appears that social-emotional processing proved more difficult for children with more severe symptoms of ASD. The findings of both studies suggest that impairments in early visual attention processes have a cascading effect on social development in ASD. This is further borne out when we consider that similar studies done with adults showed greater impairments for those with ASD; and in studies with infants at high-risk for ASD [by virtue of having an older sibling with a diagnosis], infants with slower attention orienting are more likely be diagnosed with ASD later in childhood, compared with those infant siblings who do not go on to receive a diagnosis.

The two studies offer insight into specific cognitive and brain mechanisms that may contributing to core symptoms of ASD. Our center’s long-term goal is to translate this knowledge into opportunities for improving both diagnosis and intervention, with the goal of diminishing the cascading effect of early impairments to social-emotional development.

Special Thanks...We want to thank the 100+ families that made these two studies possible by participating in research! We’d love to hear your questions and feedback about your participation at

To learn more about participating in research at CAR, visit or email us to learn about studies for neurotypical and autism spectrum participants from infancy through young adulthood.

"Why on earth would I want to do that?": The Basics of Social Motivation in Autism Spectrum Disorders

Differences in social development are among the core symptoms which define autism spectrum disorder (ASD). In the last few years, the Social Motivation Theory of autism has gained broad acceptance to explain some of the reasons why children with ASD may not profit from their social learning opportunities.

 In 2012, several CAR faculty members published a scientific review which indicates that individuals with ASD might be able to engage with social cues, but are less motivated to do so than their neurotypical peers.

Although children receive some explicit social instruction from their parents or caregivers, most social learning happens implicitly, from observation and experience. Children interpret positive social responses- a smile, a hug- as “rewards” and then repeat those behaviors.  The social motivation model suggests children with ASD have altered reward pathways in the brain, and do not feel as rewarded by the act of engaging with others. This reduces motivation for social experiences, and sets in motion a negative spiral of missing out on social learning opportunities which leads to fewer social rewards and even less interest in social interactions. In the authors’ words, “when social information is not prioritized, there are profound, cascading effects on learning about — and from — the social world”1.

Researchers across various disciplines- from neuroscience, biology, psychology and education – are using this framework to help inform their understanding of how behavioral or pharmaceutical therapies might be developed to target the motivational component of social skills- rather than focusing only on teaching specific social skills. In this way, it opens the door to powerful social learning opportunities by making the social information in children’s environment more meaningful and rewarding. To read a full commentary on Social Motivation, check out this article from SFARI’s “Spectrum” blog.

Wednesday, September 16, 2015

Getting an Evaluation for Autism Spectrum Disorder

Deciding that your child might need an evaluation for Autism Spectrum Disorder (ASD) is usually the culmination of a 3 step process.

STEP 1: THERE IS A CONCERN. A parent, family member, caregiver, teacher, speech-language pathologist, therapist, or pediatrician may be concerned that a child shows signs of developmental difference or delay. Sometimes parents have filled out a screening questionnaire that indicates a concern. Maybe a therapist, teacher, or doctor talks to a parent, or a parent expresses a concern to a healthcare professional or directly to an education agency.  If an individual expresses a concern to you, it is a good idea to contact your child’s pediatrician. The pediatrician may want you to complete a screening questionnaire or may want to observe your child. If a screening questionnaire and/or brief observation indicates there might be risk of delay or developmental differences, a referral for an in-depth evaluation is made. Even if screening questionnaires are not used, referrals might be made if a concern is expressed.

Screening Tools:
  • M-CHAT – Modified Checklist for Autism in Toddlers
  • Infant Toddler Checklist
  • SRS-2 – Social Responsiveness Scale
  • SCQ – Social Communication Questionnaire
  • ASRS – Autism Spectrum Rating Scale
  • Ages and Stages (of Child Development)
  • Denver (Developmental Screening Test)
  • SORF – Systematic Observation of Red Flags
STEP 2: REFERRAL. Parents, healthcare professionals, or therapists contact someone who is qualified to do an evaluation of development to make an appointment for an evaluation. The referral might be made to an early intervention agency or school district, a developmental pediatrician, a psychologist, a psychiatrist, or possibly a pediatric neurologist. Additional referrals may also be made to other professionals, such as audiologists, speech-language pathologists, physical therapists, and/or occupational therapists to evaluate other areas of development. Evaluations through early intervention and school districts happen relatively quickly. Sometimes the wait for a developmental pediatrician can be much longer. Parents should pursue both kinds of evaluations – educational and medical – at the same time. This is because children must be evaluated through the education system in order to receive educational services, and educational services can begin without a medical diagnosis.

STEP 3: THE EVALUATION AND RECOMMENDATIONS. There are two core elements that are necessary: (1) parent interview to gather information about the child’s birth, medical, and developmental history; and (2) clinical observation of the child’s behavior – preferably using standardized measures. Based on the information provided by a parent, the observations of the child, and the examiner’s clinical judgment, a diagnosis, if any, will be provided, along with recommendations for intervention.

Parent interviews might be done on paper, in person, or over the phone. An evaluation might take place in a home, a healthcare clinic, a medical office, a school, an early intervention center, or in a psychologist’s office. There may be more than one evaluator, who will usually meet as a team to make a diagnosis and/or recommendations for services, if needed. In-person observations are primarily play-based and are made up of various activities geared toward a child’s developmental level. Evaluators play and talk with the child and ask him or her to do simple tasks as part of the evaluation. For very young children, parents typically stay with their child throughout the evaluation.

Many of the developmental tests follow a progression of skills and include some items that the child will not be able to do. It is important to remember that this is the way development levels are determined, and all children eventually encounter activities that they do not know how to do as they go through an evaluation. At the end of the evaluation, or perhaps a week or so later, the clinician or the team will meet with the parents to discuss diagnostic impressions and recommendations for interventions and services to help the child make developmental progress. A report will be given or mailed to the parents with the full results of the evaluation and written recommendations.