ASD news briefs for Summer Table of Contents. Research 2 Interventions/Treatments 21

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1 ASD news briefs for Summer Table of Contents Topic Page Research 2 Interventions/Treatments 21

2 ASD news briefs for Summer Research Metals, nutrients in baby teeth tied to autism risk Posted on June 2, 2017 Differences in exposure to certain metals and nutrients such as lead and zinc in the womb and in early childhood may affect a child s risk of developing autism spectrum disorder, researchers say. Much of the research so far has identified genetic factors that cannot be changed, Dr. Manish Arora of the Icahn School of Medicine at Mount Sinai in New York said. Our study is an important step towards understanding modifiable risk factors such as exposure to environmental pollutants and dietary deficiencies, he told Reuters Health by , and the most sensitive time periods when these exposures are harmful. However, he stressed, it is too early to make clinical recommendations. Arora and colleagues analyzed baby teeth from 16 pairs of identical and fraternal twins in Sweden, with at least one sibling who had an ASD diagnosis by the time they were about 18 years old. For comparison, they also analyzed baby teeth from 22 twin pairs who were developing normally. A new tooth layer is formed every week or so during fetal development and childhood. Each new layer is unique and together over time they provide a record of exposure to various chemicals. Teeth are like biologic hard drives information is constantly being captured in their growth rings as teeth grow, starting in prenatal development, Arora said by . By uncovering information from teeth, we can reconstruct what an individual experienced in utero and in childhood. The team found significant differences in metal uptake between twins with ASD and their healthy siblings at certain points in development, they report in Nature Communications. In late pregnancy and the first few months after birth, for example, the teeth of children with ASD showed a higher uptake of lead a brain toxin and a lower uptake of essential nutrients manganese and zinc. What s more, three months after birth, the amount of toxic metals in teeth could predict the severity of ASD at ages 8 to 10 years.

3 ASD news briefs for Summer The authors note that the timing of unusually high or low uptake was different for each of the elements examined in the teeth. In addition, the researchers don t know if differences in the amount of toxic metals and nutrients in the teeth are due to how much a fetus or child is exposed to, or to differences in how they absorb and process these substances. The researchers also cannot say whether the disrupted uptake of these substances at particular stages of late fetal and early newborn development is a cause or an effect of autism. They suggest that these alterations likely involve multiple disruptions in the way metal uptake is regulated. It is important to remember that there is a long way to go before the results of this study can be useful to families and individual patients. More research is needed so that we can understand how nutrients, environmental toxins and genes interplay and lead to the development of autism, study coauthor Abraham Reichenberg, also with Icahn School of Medicine at Mount Sinai, said. Our genes and the genes of our babies are vulnerable to our ways of living, Dr. Eric Butter, who wasn t involved in the research, told Reuters Health by . What we eat, the air we breathe, and the things we do can change the way our genes work, Butter, who is director of the Child Development Center and Pediatric Psychology/Neuropsychology at Nationwide Children s Hospital in Columbus, Ohio, told Reuters Health by . The current study is helping researchers understand the complicated relationships between genes, toxic metals and nutrients, and how they may affect babies brains, Butter said. But the study is not saying anything about the metal exposures and vaccine controversies that have plagued the autism community, he cautioned. As in many of the best scientific advances in our field, this study opens many more important questions to be answered, Butter said. Neuroimaging technique may help predict autism among high-risk infants Posted on June 7, 2017

4 ASD news briefs for Summer Functional connectivity magnetic resonance imaging (fcmri) may predict which high-risk, 6- month old infants will develop autism spectrum disorder by age 2 years, according to a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), two components of the National Institutes of Health. The study is published in the June 7, 2017, issue of Science Translational Medicine. Autism affects roughly 1 out of every 68 children in the United States. Siblings of children diagnosed with autism are at higher risk of developing the disorder. Although early diagnosis and intervention can help improve outcomes for children with autism, there currently is no method to diagnose the disease before children show symptoms. Previous findings suggest that brain-related changes occur in autism before behavioral symptoms emerge, said Diana Bianchi, M.D., NICHD Director. If future studies confirm these results, detecting brain differences may enable physicians to diagnose and treat autism earlier than they do today. In the current study, a research team led by NIH-funded investigators at the University of North Carolina at Chapel Hill and Washington University School of Medicine in St. Louis focused on the brain s functional connectivity how regions of the brain work together during different tasks and during rest. Using fcmri, the researchers scanned 59 high-risk, 6-month-old infants while they slept naturally. The children were deemed high-risk because they have older siblings with autism. At age 2 years, 11 of the 59 infants in this group were diagnosed with autism. The researchers used a computer-based technology called machine learning, which trains itself to look for differences that can separate the neuroimaging results into two groups autism or nonautism and predict future diagnoses. One analysis predicted each infant s future diagnosis by using the other 58 infants data to train the computer program. This method identified 82 percent of the infants who would go on to have autism (9 out of 11), and it correctly identified all of the infants who did not develop autism. In another analysis that tested how well the results could apply to other cases, the computer program predicted diagnoses for groups of 10 infants, at an accuracy rate of 93 percent. Although the findings are early-stage, the study suggests that in the future, neuroimaging may be a useful tool to diagnose autism or help health care providers evaluate a child s risk of developing the disorder, said Joshua Gordon, M.D., Ph.D., NIMH Director. Overall, the team found 974 functional connections in the brains of 6-month-olds that were associated with autism-related behaviors. The authors propose that a single neuroimaging scan may accurately predict autism among high-risk infants, but caution that the findings need to be replicated in a larger group.

5 ASD news briefs for Summer Parents interactions with infants may alleviate autism features Posted by Bahar Gholipour on June 12, 2017 Teaching parents to respond to cues from babies at high risk of autism eases the severity of autism features at age 3, a new study suggests1. The research is a follow-up to a 2015 study that showed that a parent-delivered behavioral therapy decreased autism signs in their high-risk babies at age 15 months2. The new study suggests these gains persist for months to years. We seem to have a sustained effect on reducing symptoms, says lead researcher Jonathan Green, professor of child and adolescent psychiatry at the University of Manchester in the United Kingdom. It suggests we ve done something in the mechanics of the development of the child to change it. The 2015 study involved 28 babies who have an older sibling with autism. These so-called baby sibs are 20 times more likely than a typical child to be diagnosed with autism. The new study followed the same babies until age 3. The work appeared 10 April in the Journal of Child Psychology and Psychiatry. The study is the first methodologically strong, randomized trial of early intervention for highrisk infants, says Connie Kasari, professor of human development and psychology at the University of California, Los Angeles, who was not involved in the work. The researchers have done a careful follow-up of their infants also a first. Home base: Only about one in five baby sibs receives an autism diagnosis. But even those who do not meet the criteria for autism can show features of the condition, such as low social interest or attention problems. These features can impede their ability to interact with their parents. The children in the study come from the British Autism Study of Infant Siblings (BASIS). When they were 9 months old, their parents had the first of 12 individualized training sessions with a therapist. The training spanned five months.

6 ASD news briefs for Summer The importance of this study lies in emphasizing the need for a shift in focus from direct treatment of the child towards interventions that target the process of social interaction between the child and the caregiver, says Gordon Ramsay, director of the Spoken Communication Laboratory and assistant professor of pediatrics at Emory University in Atlanta, Georgia, who was not involved with the new work. During the sessions, parents watched video recordings of themselves interacting with their children. They received feedback on how to respond to their baby s facial expressions and gestures. They practiced their new skills for at least 20 minutes every day. The parents of another 26 baby sibs did not receive any training. At the end of the five months, the researchers measured early signs of autism in both groups of baby sibs, using the Autism Observation Scale for Infants. They used two other assessments to gauge the quality of interaction between the babies and their parents. By these measures, the training seemed to improve parent-child interactions overall. Babies in the treatment group also seemed to have fewer early signs of autism, the researchers reported in the 2015 study2. But the results varied significantly across the small sample, suggesting the effect could have been due to chance, Green says. Preemptive program: In the new work, the researchers assessed the children at ages 2 and 3 old enough to be evaluated for autism using the Autism Diagnostic Observation Schedule. Four children in the training group received an autism diagnosis, compared with two of the controls. But this difference was not statistically significant. The quality of parent-child interactions was still better in the training group than in the control group at age 2, however. And the 2- and 3-year olds whose parents received training also showed less pronounced autism features than controls did. These findings also did not reach statistical significance individually. But when the researchers combined the measures over the three time points, they found that the treatment offers a significant overall benefit. The work hints that preemptive therapies, in which parents address early signs of autism, may help their children develop more typically. But we need larger studies to be confident that the strategy works, says Lindee Morgan, assistant professor of pediatrics at Emory University, who was not involved with the new work. We are far from having the data needed to recommend preemptive interventions for all baby siblings, she says.

7 ASD news briefs for Summer Green agrees. Larger studies could also assess whether the therapy lowers the chances of an autism diagnosis, he says. Fevers During Pregnancy May Raise Autism Risk, Study Shows Posted by Maggie Fox on June 15, 2017 There s more evidence linking infections during pregnancy with a child s risk of autism. The new report, out Tuesday, shows that women who had infections while pregnant were more likely to have children with autism. The more fevers they had, the higher the risk and the second trimester of pregnancy seemed to be an especially important time. Women who had fevers in the second trimester of pregnancy were 40 percent more likely to have a child with autism. The findings, published in the journal Molecular Psychiatry, support the theory that it might be the body s response to an infection rather than a bacteria or virus that s damaging the developing baby s brain. Risks increased markedly and dose dependently with fever frequency, with particularly strong effects after 12 weeks gestation, Dr. Mady Hornig of Columbia University and colleagues wrote in their report. Women who took acetaminophen to lower their fevers were less likely to have a child later diagnosed with autism, although it s too early to say whether the acetaminophen the active ingredient in Tylenol lowered the risk. None of the women who took ibuprofen had children with autism but so few women took ibuprofen that it s hard to say what the effect was, the researchers noted. This study, using a large, well-characterized sample, confirms the association between fever and risk for autism spectrum disorder, said Thomas Frazier, chief science officer for Autism Speaks, who was not involved in the study. The research also clarifies that the relationship is strongest in the second trimester. Interestingly, the strength of the relationship increases substantially with three or more maternal fevers, and anti-fever medications like acetaminophen may reduce the risk of autism.

8 ASD news briefs for Summer Columbia s Dr. Ian Lipkin believes it may be the fever or some other aspect of the body s inflammatory response to an infection that may be damaging the brain of the fetus. Lipkin, who took part in the study, also worked on research published earlier this year linking herpes infections with autism. Viruses can infect and damage a developing baby's brain Zika is the most notorious now, but rubella and cytomegalovirus can also cause severe birth defects. The research also clarifies that the relationship is strongest in the second trimester. Lipkin believes that with autism, however, it's the mother's immune response that's causing the damage. It may be that inflammatory chemicals such as cytokines are crossing the placenta and affecting the developing brain of the fetus, he said. Surveys by the Centers for Disease Control and Prevention find that as many as than 2 percent of U.S. kids have been diagnosed with autism anywhere between 1 in 68 and 1 in 45 children. The autism spectrum refers to a broad range of symptoms, from the relatively mild social awkwardness of Asperger's syndrome to profound mental retardation, debilitating repetitive behaviors and an inability to communicate. There's no cure and no good treatment. There are genetic links. If one twin has autism, the other twin is very likely to. There's also growing evidence that infections in pregnancy might play a role. A 2013 study found that women who had the flu while they were pregnant were twice as likely to have a child later diagnosed with autism. Those who had a fever lasting a week or longer perhaps caused by flu or maybe by something else were three times as likely to have an autistic child. In the study discussed Tuesday, the Columbia team used a survey of 95,000 children born in Norway. The mothers were followed in real time during their pregnancies and all infection and fevers were documented. Then the children were followed up to see which ones developed autism. Maternal exposure to second-trimester fever was associated with increased autism spectrum disorder risk, the team wrote. That doesn t mean women should panic if they get a fever during pregnancy. It s common for women to have some sort of fever while pregnant at least 20 percent of pregnant women in the U.S. have fevers at some point.

9 ASD news briefs for Summer Prozac Improves Autism Traits in Mouse Model Posted by Tim Newman on June 21, 2017 Researchers found that Prozac, given during development, can reduce autism-like traits in mouse models of the disorder. Symptoms of autism spectrum disorder (ASD) are varied but often include difficulty with socializing and exhibiting repetitive behaviors. An estimated 1 in 68 children is diagnosed with ASD in the United States. Worryingly, the number of diagnoses made is steadily rising. Despite its prevalence, the exact causes of ASD are not yet known. Because of this, treatment options are also severely lacking. New research carried out at the RIKEN Brain Science Institute in Japan set out to investigate the role of serotonin in the development of ASD. Led by Toru Takumi, the work is published this week in the journal Science Advances. Recent work has shown that individuals with ASD have a high number of genomic mutations across a range of genes. Using this knowledge, Takumi s group designed a mouse model of ASD by duplicating one of the most common copy variations. The resulting mice displayed some of the characteristics of ASD in humans, such as behavioral inflexibility and poor social interaction. Interestingly, these mice had lower levels of serotonin in their brains during development something that has also been demonstrated in humans with ASD. Although abnormalities in the serotonin system have been thought to be part of the ASD pathophysiology, the functional impact of serotonin deficiency in ASD was totally unknown, said Takumi. In their study, the Japanese team wanted to understand how lower levels of serotonin can affect the behavior of neurons and the impact that this has on behavior.

10 ASD news briefs for Summer Firstly, the team demonstrated that the neurons in the brain area with highest serotonin levels were less active than in normal, control mice. Next, they studied the region of the brain that receives neurons from these particular serotonergic neurons. Individuals with ASD are known to have abnormal responses in the sensory regions of their brain. Takumi and his team found similar discrepancies in the part of the mouse brain that deals with whisker movements. In the ASD mouse model, rather than whisker movements being confined to discrete areas, they were spread more liberally across the sensory cortex. This overlapping of regions means that it would be harder to distinguish sensations. The team presumed that, because there was activity in normally inactive neurons, there may be reduced inhibition. The team confirmed this theory; they found that there were fewer inhibitory synapses and less frequent inhibitory inputs to the sensory area. This discovery led to the next phase of the experiment. As first author Nobuhiro Nakai explains, Because the sensory region was receiving abnormally low serotonin input, we reasoned that giving infant mice serotonin therapy might reduce the imbalance and also rescue some of the behavioral abnormalities. Does increased serotonin alter ASD behavior? To answer this question, the researchers used a selective serotonin reuptake inhibitor (SSRI) called fluoxetine, which is also known as Prozac. SSRIs are common drugs used to treat depression and anxiety disorders. They gave Prozac to the mice 3 weeks after birth, a point in time when serotonin is known to be reduced in the mouse model. Sensory neurons in the mice treated with SSRIs did, as expected, exhibit more normal inhibitory responses. Once the inhibitory/excitatory balance had been brought back in line, the team tested to see whether or not the mice s behavior would also change in line. To examine this, they gave the mice a choice of spending time near an empty cage, or near a cage that housed an unknown mouse. Normally, mice choose to spend more time next to a cage with an unknown rodent. ASD model mice, however, choose to spend time next to the empty cage. The ASD mice given Prozac during development chose to spend more time close to the unknown mouse. Also, ASD mouse pups produced more vocalizations, which is a measure of anxiety, while those given Prozac did not.

11 ASD news briefs for Summer The findings may offer a new avenue of research into ASD and potential treatments. Of course, there will need to be much more research, as Takumi explains: Our genetic model for ASD is one of many, and because the number of genetic mutations associated with ASD is so high, we need to investigate differences and common mechanisms among multiple genetic ASD models. Additionally, before we can administrate SSRIs to patients with ASD, we must study the effects of SSRIs in more detail, especially because adverse effects have been reported in some animal studies. Although the hunt for ASD treatments will be ongoing for many years to come, the current findings offer fresh hope. How an autism gene mutation alters brain development Posted by Honor Whiteman on June 30, 2017 Researchers have shed light on how CHD8 gene mutations alter brain development and impair cognitive functioning. By analyzing the brains of mice, researchers have discovered how mutations in a gene called CHD8 may alter brain development and cognitive functioning to cause autism. Researchers from the United States and Canada found that CHD8 gene mutations altered gene expression in mice, impairing their cognitive functioning and increasing brain volume. Both of these characteristics are present in humans with autism who have CHD8 gene mutations. What is more, the researchers found that the changes in gene expression as a result of CHD8 gene mutations arise in early brain development, and they continue throughout the course of a lifetime. The study - led by Alex Nord, of the University of California-Davis - was recently published in the journal Nature Neuroscience. According to the Centers for Disease Control and Prevention (CDC), around 1 in 68 children in the U.S. have been diagnosed with autism, with the condition being around 4.5 times more common among boys than girls.

12 ASD news briefs for Summer While the precise causes of autism are unclear, studies have indicated that environmental and genetic factors play a role. Mutations in the CHD8 gene are considered to be one such factor. Studying CHD8 gene mutations in mice Located on chromosome 14, CHD8 is known to encode a protein responsible for DNA packaging, which regulates gene expression in cells during development. Normally, humans have two functioning copies of the CHD8 gene. In some rare cases of autism, however, one copy of this gene is mutated and its function is therefore lost. Nord and colleagues used mouse models for their study, in order to gain a better understanding of how CHD8 gene mutations influence brain development. The team notes that around 85 percent of mouse genes are coded in a similar way to human genes. This means that changes in the DNA of mice will simulate changes in human DNA, making the rodents a good model for studying genetic mutations. What is more, the researchers point out that mice display behaviors that are similar to those of humans. "Behavioral tests with mice give us information about sociability, anxiety, and cognition," explains Nord. "From there, we can examine changes at the anatomical and cellular level to find links across dimensions. This is critical to understanding the biology of disorders like autism." How CHD8 mutations affect the brain Using CRISPR/Cas9 gene editing, the researchers bred mice that only possessed one copy of the CHD8 gene, and they looked at how this affected their brain development. In mice with two functioning CHD8 genes, the researchers found that CHD8 gene expression peaked early on in brain development. But in mice with only one functioning copy of CHD8, cell proliferation increased significantly in early brain development, and the rodents exhibited a larger brain size, which is often the case in humans with autism. Additionally, the team found that mice with a CHD8 gene mutation experienced gene expression changes for the rest of their lives. Importantly, the researchers found that such changes interfered with the function of synapses, which are structures that enable brain cell communication. These brain changes led to cognitive impairment in the rodents, including poor learning and memory.

13 ASD news briefs for Summer The findings suggest that CHD8 gene mutations do not only affect brain development, but they also continue to affect brain functioning throughout adulthood. The researchers believe that their results offer insight into one of the underlying causes of autism, which could pave the way for much needed new treatments for the condition. "For years, the targets of drug discovery and treatment have been based on an unknown black box of what's happening in the brain," says Nord. Oxytocin Nasal Spray May Boost Social Skills in Children with Autism Posted by Jessica Wright on July 11, 2017 Treatment with the hormone oxytocin improves social skills in some children with autism, suggest results from a small clinical trial. The results appeared today in the Proceedings of the National Academy of Sciences1. Oxytocin, dubbed the love hormone, enhances social behavior in animals. This effect makes it attractive as a potential autism treatment. But studies in people have been inconsistent: Some small trials have shown that the hormone improves social skills in people with autism, and others have shown no benefit. This may be because only a subset of people with autism respond to the treatment. In the new study, researchers tried to identify this subset. The same team showed in 2014 that children with relatively high blood levels of oxytocin have better social skills than do those with low levels2. In their new work, the researchers examined whether oxytocin levels in children with autism alter the children s response to treatment with the hormone. They found that low levels of the hormone prior to treatment are associated with the most improvement in social skills. We need to be thinking about a precision-medicine approach for autism, says Karen Parker, associate professor of psychiatry at Stanford University in California, who co-led the study. There s been a reasonable number of failed [oxytocin] trials, and the question is: Could they have failed because all of the kids, by blind, dumb luck, had really high baseline oxytocin levels?

14 ASD news briefs for Summer The study marks the first successful attempt to find a biological marker that predicts response to the therapy. This study is suggestive of a hormonal-based biomarker for oxytocin treatment, which makes sense and is a promising step forward, says Adam Guastella, professor of psychology at the Brain and Mind Centre at the University of Sydney in Australia, who was not involved in the study. Hormone help The researchers enrolled 34 children with autism, aged 6 to 12 years. Parents gave their children a nasal spray twice a day for four weeks; 16 children got a spray containing oxytocin, and 18 got a spray with placebo. (Two of the children in the oxytocin group later dropped out of the study.) The researchers measured oxytocin levels in the children s blood at the start and end of the trial. They assessed the children s social skills using a parent questionnaire called the Social Responsiveness Scale (SRS) and used other tests to assess the drug s effects on repetitive behaviors and anxiety levels. Based on SRS scores alone, oxytocin treatment did not lead to a statistically significant improvement in social skills. But when the researchers built a statistical model that accounted for the children s oxytocin levels at the trial s start, they found that the children who received oxytocin improved more on the SRS than did those on the placebo. The children with the lowest initial blood levels of oxytocin generally showed the most improvement. Some children who received the placebo also showed an improvement in their social skills. These children also showed a rise in oxytocin levels over the course of the study. This indicates that simply participating in the study boosted their oxytocin levels, and may underlie their improvement, Parker says. Boosting oxytocin levels in other ways say, through a behavioral intervention could also be beneficial, she says. The treated children showed no decrease in repetitive behaviors or anxiety, suggesting that the findings are specific to social skills. The therapy had no serious side effects. Looking ahead Oxytocin levels vary naturally among people, and may even change throughout the day. The researchers tried to mitigate some of this variability by drawing each child s blood at roughly the same time each day. Still, the change in oxytocin levels in the placebo group could be a result of natural variation and might not be meaningful, says Linmarie Sikich, associate director of the Duke Center for Autism and Brain Development in Durham, North Carolina, who was not involved in the study.

15 ASD news briefs for Summer Researchers also note that the trial did not assess oxytocin s long-term effects. Should oxytocin be found effective, no one is going to use it for four weeks and stop. We have to make sure that long-term administration is safe, says co-lead researcher Antonio Hardan, professor of psychiatry and behavioral sciences at Stanford University. Confirming oxytocin s effectiveness as an autism treatment requires larger, longer-term studies. With that goal in mind, Sikich and her colleagues have enrolled nearly 300 people with autism in a placebo-controlled 24-week trial of the hormone. The placebo and treatment groups will then receive treatment for another six months. The team is measuring the participants blood levels of oxytocin before, during and after treatment. They are also monitoring factors that alter the expression of the oxytocin gene, and of other genes involved in the same pathway. This story was originally published on Spectrum. In autism, genes drive early eye gaze abnormalities Posted by Jim Dryden on July 12, 2017 New research has uncovered compelling evidence that genetics plays a major role in how children look at the world and whether they have a preference for gazing at people s eyes and faces or at objects. The discovery by researchers at Washington University School of Medicine in St. Louis and Emory University School of Medicine in Atlanta adds new detail to understanding the causes of autism spectrum disorder. The results show that the moment-to-moment movements of children s eyes as they seek visual information about their environment are abnormal in autism and under stringent genetic control in all children. The study is published online July 12 in the journal Nature. Now that we know that social visual orientation is heavily influenced by genetic factors, we have a new way to trace the direct effects of genetic factors on early social development, and to design interventions to ensure that children at risk for autism acquire the social environmental inputs they need to grow and develop normally, said lead author John N. Constantino, MD, the

16 ASD news briefs for Summer Blanche F. Ittleson Professor of Psychiatry and Pediatrics at Washington University. These new findings demonstrate a specific mechanism by which genes can modify a child s life experience. Two children in the same room, for example, can have completely different social experiences if one carries an inherited tendency to focus on objects while the other looks at faces, and these differences can play out repeatedly as the brain develops early in childhood. The researchers studied 338 toddlers ages 18 to 24 months using eye-tracking technology, developed at Emory, allowing them to trace young children s visual orientation to faces, eyes or objects as the children watched videos featuring people talking and interacting. The children, who were part of the Missouri Family Registry, a database of twins that is maintained at Washington University School of Medicine, included 41 pairs of identical twins such twins share 100 percent of their DNA and 42 sets of fraternal twins who share only about 50 percent of their DNA. In addition, the researchers studied 84 unrelated children and 88 children diagnosed with autism spectrum disorder. Constantino, with fellow investigators Warren R. Jones, PhD, and Ami Klin, PhD, of Emory University School of Medicine, evaluated the eye-tracking data. Each twin was tested independently, at different times, without the other twin present. How much one identical twin looked at another person s eyes or face was almost perfectly matched by his or her co-twin. But in fraternal twins, eye movements in one twin accounted for less than 10 percent of the variation in the eye movements of his or her co-twin. Identical twins also were more likely to move their eyes at the same moments in time, in the same directions, toward the same locations and the same content, mirroring one another s behavior to within as little as 17 milliseconds. Taken together, the data indicate a strong influence of genetics on visual behavior. The moment-to-moment match in the timing and direction of gaze shifts for identical twins was stunning and inferred a very precise level of genetic control, said Constantino, who directs the William Greenleaf Eliot Division of Child and Adolescent Psychiatry at Washington University. We have spent years studying the transmission of inherited susceptibility to autism in families, and it now appears that by tracking eye movements in infancy, we can identify a key factor linked to genetic risk for the disorder that is present long before we can make a clinical diagnosis of autism. The effects persisted as the children grew. When the twins were tested again about a year later, the same effects were found: Identical twins remained almost perfectly matched in where they looked, but fraternal twins became even more different than they were when initially evaluated. Autism spectrum disorder is a lifelong condition that affects about 1 in 68 children in the United States. It is known to be caused by genetic factors, and earlier work by the Emory University

17 ASD news briefs for Summer team had shown that babies who look progressively less at people s eyes, beginning as early as 2-6 months of age, have an elevated risk for autism. Meanwhile, Constantino and others in the group have studied how subtle behaviors and symptoms that characterize autism aggregate in the close relatives of individuals with autism, as a way to identity inherited susceptibilities that run in families and contribute to autism risk. Studies like this one break new ground in our understanding of autism spectrum disorder: Establishing a direct connection between the behavioral symptoms of autism and underlying genetic factors is a critical step on the path to new treatments, said Lisa Gilotty, PhD, chief of the Research Program on Autism Spectrum Disorders at the National Institute of Mental Health, which provided support for the study in tandem with the Eunice Kennedy Shriver Institute of Child Health and Human Development. Those new treatments could include interventions that motivate very young children to focus their gazes more on faces and less on objects. Testing infants to see how they are allocating visual attention represents a new opportunity to evaluate the effects of early interventions to specifically target social disengagement, as a way to prevent the most challenging disabilities associated with autism, said senior author Warren R. Jones, PhD, director of autism research at the Marcus Autism Center at Emory. Such interventions might be appropriate for infants showing early signs of risk or those who have been born into families in which autism has affected close relatives. In addition, learning why some infants who tend to not look at eyes and faces develop without social disability is another priority. The small percentage of healthy children who tended to avoid looking at eyes and faces may provide researchers with insight on how to successfully compensate for those tendencies and therefore inform the development of higher-impact interventions that will produce the best possible outcomes for infants with inherited susceptibility to autism. In addition to Constantino, the research team at Washington University included Anne L. Glowinski, MD, a professor of child psychiatry and associate director of child and adolescent psychiatry; Natasha Marrus, MD, PhD, an assistant professor of child psychiatry; and Stefanie F. Kennon-McGill, PhD, a postdoctoral research associate in psychiatry. Stress, not diet, likely source of GI problems in children with autism

18 ASD news briefs for Summer Posted on July 14, 2017 Stress, not dietary intake, contributes to gastrointestinal issues in children with autism spectrum disorder, according to a presentation from the 2017 International Meeting for Autism Research. Unfortunately, it s not uncommon for those with autism to experience constipation, irritable bowel syndrome, abdominal pain and other gastrointestinal issues, Brad Ferguson, PhD, postdoctoral research fellow in the department of radiology at the University of Missouri School of Medicine and the University of Missouri Thompson Center for Autism and Neurodevelopmental Disorders, said in a press release. We sought to find out whether nutritional intake in their individual diets was associated with gastrointestinal issues. In prior research, Ferguson and colleagues found a correlation between autonomic functioning, cortisol stress response and lower GI tract symptomology; however, the relationship between diet and GI symptoms among patients with autism spectrum disorder (ASD) remains largely unknown. In the present study, the researchers analyzed dietary composition in the same cohort of participants to determine whether nutrition contributed to the relationship between the response to stress and GI functioning in ASD. Researchers examined the GI symptoms, stress response and diet of 75 children aged 5 to 18 years recruited from the Autism-Speaks Autism Treatment Network (ATN). Caregivers completed questionnaires to measure the participant s GI symptoms and food intake over the past month. The investigators then compared the reported instances of GI problems with 32 different nutrients found in a standard diet. Participants also underwent two stress tests to determine cortisol response and heart rate variability. Analysis revealed that the most common GI disorders were functional constipation (42.5%), IBS (11.7%), lower abdominal pain associated with bowel symptoms (9.2%) and upper pain associate with bowel symptoms (7.5%). Although initial evaluation showed a positive association between GI tract symptoms and total dietary fiber (P =.042) and vitamin B6 intake (P =.03), they were not significant after adjusting for the 32 nutrients, indicating no significant correlations between nutritional composition and GI tract issues in this cohort of patients with ASD. In contrast, the data did show a positive association between lower GI tract symptoms and cortisol response to stress-inducing stimuli (95% CI, ). Contrary to what you may initially think, dietary composition does not appear to be a driving factor between stress response and gastrointestinal function in this sample, Ferguson said. More research is needed to better understand the causes of these issues, but an increased reaction to stress does appear to be a contributing factor.

19 ASD news briefs for Summer Females with autism show greater difficulty with day-to-day tasks than male counterparts Posted by Amy Goodwin on July 14, 2017 Women and girls with autism may face greater challenges with real world planning, organization and other daily living skills, according to a study published in the journal Autism Research. Led by researchers within the Center for Autism Spectrum Disorders at Children's National Health System, the National Institute of Mental Health, and The George Washington University, the study is the largest to date examining executive function-including the ability to make a plan, get organized, and follow through on the plan as needed-and adaptive skills-ability to perform basic daily tasks like getting up and dressed or making small talk- in women and girls with ASD. "Our goal was to look at real world skills, not just the diagnostic behaviors we use clinically to diagnose ASD, to understand how people are actually doing in their day to day lives," says Allison Ratto Ph.D.,, a psychologist in the Center for Autism Spectrum Disorders at Children's National and one of the study's authors. "When parents were asked to rate a child's day-to-day functioning, it turns out that girls were struggling more with these independence skills. This was surprising because in general, girls with ASD have better social and communication skills during direct assessments. The natural assumption would be that those communication and social skills would assist them to function more effectively in the world, but we found that this isn't always the case." The study collected parent-reported data from several rating scales of executive function and adaptive behavior, including the Behavior Rating Inventory of Executive Function, Parent Form (BRIEF) and the Vineland Adaptive Behavior Scales-II (VABS-II). The group included 79 females and 158 males meeting clinical criteria for autism spectrum disorders, ranging in ages from 7 to 18 years old. The groups were matched for intelligence, age and level of autism and ADHD symptoms. The findings are part of a growing body of research focused on how ASD may affect females differently than males. The ratio of girls to boys with autism is approximately three to one. As a result of the larger numbers of males, existing data is predominantly focused on traits and

20 ASD news briefs for Summer challenges in that population. This is especially true in clinical trials, where enrollment is overwhelmingly male. "Our understanding of autism is overwhelmingly based on males, similar to the situation faced by the medical community once confronted with heart disease research being predominantly male," notes Lauren Kenworthy, Ph.D., director of the Center for Autism Spectrum Disorders and the study's senior author. "We know how to identify signs, symptoms, and treatments for autism in males, but we know very little about unique aspects of it in females." The historical lack of specific discovery around how autism presents in females may contribute to misdiagnosis or delay, and prevent implementation of necessary interventions. Such delays can have a major impact on outcomes, as recent research has demonstrated the critical importance of early diagnosis and intervention in ASD. "Our focus in caring for children with autism is equipping ALL of them with strategies and skills to allow them to function and succeed in day-to-day living," Dr. Kenworthy continues. "This study highlights that some common assumptions about the severity of challenges faced by girls with ASD may be wrong, and we may need to spend more time building the adaptive and executive function skills of these females if we want to help them thrive." "Enhancing our understanding of how biological differences change the presentation of autism in the long term is crucial to giving every person with ASD the tools they need to succeed in life," she concludes.

21 ASD news briefs for Summer Interventions/Treatments Telehealth reduces wait time, improves care for children with autism living in remote areas Posted on June 1, 2017 Long wait times have been a persistent issue for families waiting to see an autism specialist, with waits often exceeding a year. Additionally, children with autism living in rural areas have added costs associated with traveling long distances for health care. To address these issues, ECHO Autism, a University of Missouri program, has been successfully training primary care providers to diagnose and manage autism spectrum disorders. Now, Kristin Sohl, associate professor of child health and the director of ECHO Autism, is preparing to expand the program with ECHO Autism partner sites serving Alabama, Alaska and under-served Navajo communities in New Mexico and Arizona. ECHO Autism also is set to expand globally through partner sites in Kenya. In the past year, Sohl has conducted autism specific trainings for ECHO Uruguay. "Since the initial studies of ECHO Autism, nearly 250 health providers have received training on best-practice care," Sohl said. "The program effectively increases the capacity for health care in underserved communities, which means that families can get the answers they need without traveling or waiting to see a specialist." Launched in March 2015, ECHO Autism is a partnership between the MU Thompson Center for Autism and Neurodevelopmental Disorders, MU Health, and the Missouri Telehealth Network Show-Me ECHO program. ECHO Autism clinics are conducted using high-quality, secure video conferencing technology to connect participating primary care clinics to a panel of experts. Initial studies of the program have found that participating primary care providers demonstrated significant improvements in confidence across all sectors of health care for children with autism, including screening and identification, assessment and treatment of medical and psychiatric conditions, and knowledge of and referral to available resources. "The success we have seen in Missouri and in other areas where ECHO Autism has been replicated means that this model can work in even more remote areas," Sohl said. "Expanding the program from Africa to Alaska will help families around the world." Micah Mazurek, associate professor of health psychology in the School of Health Professions, and Rachel Brown, professor of clinical psychiatry in the MU School of Medicine, co-authored the recently published paper, "ECHO Autism: using technology and mentorship to bridge gaps, increase access to care, and bring best practice autism care to primary care," which was featured

22 ASD news briefs for Summer in Clinical Pediatrics. ECHO Autism is modeled after Project ECHO at the University of New Mexico. New Protocol Predicts Effectiveness of Interventions for Adult Autism Posted by Rick Nauert PhD on June 15, 2017 Researchers have created a protocol to predict individual treatment effectiveness for adults on the autism spectrum. Investigators from the Center for BrainHealth at the University of Texas at Dallas and George Washington University used functional magnetic resonance imaging (fmri) to identify if a virtual environment-based training program lead to changes in brain areas that are associated with social skills. Researchers discovered that adults on the autism spectrum with greater activity in the social brain network prior to the training improved more in emotion recognition than those who showed less activity. We found that when participants showed more brain activation in certain regions within the social brain network, while viewing digitally represented biological motion motion that symbolizes something a human might do, such as playing pat-a-cake the intervention was more beneficial to the participants, explained Dr. Daniel Yang, assistant research professor at George Washington University and Children s National Health System. Whereas if these social brain network regions did not show much activation, we observed that the person may not benefit from the intervention at this particular time but, as the brain is constantly changing, could benefit in the future, for example, by increasing pretreatment activation in these regions. The U.S. Interagency Autism Coordinating Committee (IACC) named Yang s finding utilizing this predictive method with pediatric populations in a separate study one of the top 20 advances in autism research of This study advances us one step closer toward the goal of targeted, personalized treatment for individuals with autism, said Dr. Yang.

23 ASD news briefs for Summer We are very happy that this predictive method may be potentially able to help children, as well as adults on the spectrum, know which training might be worth their time and money based on their current brain function. For the study, seventeen participants between the ages of 18 and 40 years diagnosed with autism spectrum disorder were recruited from the Center for BrainHealth and the Yale Child Study Center at Yale University where Yang worked at the study s inception. Participants completed a five-week training program that met twice a week for one hour. The clinician-led, strategy-based intervention allowed participants to role play social interactions in a virtual environment. The training focuses on three core social strategies: recognizing others, responding to others and self-assertion, said Tandra Allen, head of virtual training programs at the Center for BrainHealth, who provided the trainings. We use avatars to make the complex social situations such as dealing with confrontation, job interviews, or a blind date feel more approachable to practice while still drawing on the same emotions that a person would experience in the real world. Before the 10 hours of training, participants underwent brain imaging. While in the fmri scanner, the participant passively viewed a series of animations. Some of the images represented a human in motion, such as a person playing pat-a-cake, while other images were scrambled and did not represent something a human would do. Two clusters of activity stood out as significantly correlating with training success. The first is an area on the left side of the brain responsible for language processing, specifically conflicts in meanings. The other resides on the right side of the brain and is responsible for processing non-verbal social-emotional cues, for example, being able to look at a person s facial expression and ascertain emotional states such as fear, anger or joy. Treatment effectiveness was measured by behavioral changes in two distinct domains of social abilities: 1.emotional recognition, or the change in socio-emotional processing abilities and; 2.theory of mind, or the change in socio-cognitive processing abilities. There is very limited intervention research for adults on the autism spectrum, so being able to help make a leap forward in creating individualized treatment programs for them is very important to the field, said Yang.