The Kolevzon Family at the Ride FAR event last year

by Ana Kolevzon, 12 years old

Autism has always been talked about in our family of four. That’s because my sister, Mila, 10, and I are lucky enough to have a dad who works to help people with #autism every day for his job. My dad is Dr. Alexander Kolevzon MD, Child Psychiatrist and Professor at the Icahn School of Medicine at Mount Sinai in New York City. He works at the Seaver Autism Center at The Mount Sinai Hospital to provide therapy and treatment to boys and girls who are diagnosed with autism spectrum disorder, teaches young researchers, and also conducts research himself.

My family also knows firsthand what it’s like to have a family member with autism. My cousin, Roy, 20, was diagnosed with autism when he was young. I’m really close with him even though he lives in Israel and it’s hard to see how the symptoms of autism affect him every day of his life. He is the sweetest, most compassionate person, and I always knew I wanted to take action in some way to help him and others with autism.

This year will be my third year riding my bike at Wall Street Rides FAR – for Autism Research, which is in White Plains, New York on October 7th and benefits the Autism Science Foundation (ASF). ASF is a nonprofit organization that provides funds to scientists to conduct #research to find out what the causes of autism are, and to develop better treatments for people like Roy. The first year, my dad and I rode the 10-mile course and then took on the 20-mile course in the second year of the ride. I have been riding my #bike since I was five years old but this was harder than I thought it would be! I didn’t mind, though, because the ride through the colorful fall leaves is beautiful and I love spending time with my dad for a cause that’s so important to us. Also, the whole time that we’re riding, we’re looking forward to the great food and fun music at the finish festival. This year will be the first time that my sister, Mila, will be old enough to ride her bike with us – I can’t wait!

I’m so glad that although my sister and I are still young, we have the opportunity to raise money and awareness about something that has impacted my family in so many different ways. Autism not only affects the person who has the diagnosis but also their family and friends who support them every day. Every mile that I ride and every dollar that I raise helps ASF and researchers get closer to finding more ways to help people like my cousin. It’s important that people everywhere support organizations like the Autism Science Foundation – and it can be done by doing something that you love, like riding your bike!

To register for Wall Street Rides FAR – for Autism Research on October 7th, please visit http://wallstreetridesfar.org/.


Ana and her father, autism researcher Alex Kolevzon, MD

By Alison Singer and Alycia Halladay

Spectrum News recently published “What Baby Siblings Can Teach Us About Autism,” an in-depth exploration of baby siblings research, and particularly initiatives made possible by the Baby Siblings Research Consortium (BSRC), which ASF  funds.  We are grateful that the writer, Ingfei Chen, and Spectrum have highlighted the impactful work that is being done in what we believe is an extremely significant and exciting area of autism science. However, there are some points of clarification about the article that we think are important to share.

The BSRC is a group of 26 principal investigators around the world who have spent nearly two decades investigating the very earliest signs and symptoms of autism by tracking behavior from early infancy.  Because infant siblings show a ~15x greater increase in ASD diagnosis compared to those without such a family connection, the younger sibs of children with autism provide an enriched pool, as 20% of them will likely be diagnosed with autism vs. 1-2% in the general population.  Such an approach is not unique to autism, but has been an especially productive avenue to understand ASD symptoms.

Baby siblings research has been a major source of information to families affected by ASD.  Even though 80% of the children studied will not go on to receive an ASD diagnoses, we have learned a tremendous amount from the 20% that did.  Because all siblings are closely tracked from infancy, clinicians are now more able to help the 80% without a diagnosis who still face considerable challenges.   And while it is true that baby sibling research has not yielded a definitive diagnostic test for children at 12 months of age,  these studies are hardly a failure.  Baby sibs research has identified or confirmed several early warning signs, including lack of response to name, abnormal eye gaze and motor delays.  Baby sibs research has helped identify new autism candidate genes that have yielded new targets for drug intervention.  And importantly (as the Spectrum story describes), new imaging work through a partnership between the BSRC and the IBIS network has identified two critical new brain based biomarkers that hold important future promise.   The Spectrum report mentioned only one of many such biologically based markers of early risk being explored.  For example, investigators are exploring other biomarkers that may be more practically implemented, like eye gaze and EEG.

Autism is heterogeneous and highly complex. It requires high risk, high reward type studies.  To put it in perspective, when the BSRC first started conducting studies, genetic researchers were searching for what they thought would be one or two autism genes.  They now know there are at least 60 autism genes.  Our family members with autism need us to think boldly and invest wisely. Instead of considering the early BSRC studies “misguided” because they failed to produce a diagnostic test, we should focus on the fact that these longitudinal studies have produced important advances in diagnosis, intervention, family support, and neurobiology and have spawned important lines of research across the ASD spectrum.  Most importantly, these early markers of an autism diagnosis have given families across the world an opportunity to receive the earliest possible intervention.  The benefits of these interventions have been well documented.

We consider the BSRC a success for families and look forward to new and important discoveries to come that will improve the lives of people with autism and their families.

By Alison Singer, President and Co-Founder of the Autism Science Foundation

For the past several years, parents of children with autism and adults with autism have described unusual pain responses in individuals with autism.  Because people with autism don’t communicate the same way as those without autism, they  may not be able to express their response to physical pain. Or, it may be possible that sensory issues may somehow change pain processing, or alter the ability to process a stimulus as painful or not painful.

Very little research has been done to address this critical issue affecting those with ASD and impacting their clinical care plans.  One reason why is that studying pain would require knowingly exposing people with and without autism to painful stimuli.

Beginning this summer, ASF will be funding a new study by Dr. Michelle Failla and Dr. Carissa Cascio at Vanderbilt University that we believe will enable us to begin to understand pain response in people with autism. This study will examine both verbal responses to pain, as well as nonverbal responses like heart rate, facial expression and stress response, to a mild stimuli in adults with ASD.


Alison Singer is hooked up to the heart rate  and galvanic skin response monitors

The findings will help clinicians understand pain sensitivity so that new strategies to assess and manage pain can be developed.

The study protocol was approved by the IRB of Vanderbilt University and exceeded all safety requirements. Nonetheless, before we felt comfortable recommending that adults with autism enroll in the study, ASF Chief Science Officer Dr. Alycia Halladay and I traveled to Nashville to experience the pain stimuli personally. We both felt strongly that we couldn’t ask individuals to subject themselves to pain unless we had experienced it ourselves and could offer a first-person account.


A small hotpad is placed on the calf by Michelle Failla.

Three short “tasks” were involved in the study.  Each measured our pain sensitivity to heat delivered by a small thermode (a hot plate, approximately 1 inch by 1 and ½ inches) placed on our calf. During the tasks, we felt heat for a short period and then were asked to rate the amount of pain we felt on a scale of 0 to 100 (0 indicating no pain and 100 indicating the worst pain).     The highest amount of pain we felt in any task was 60-70 but most were lower and several were 0.  In the third task, the small hot plate was administered for bursts of 15 seconds and again we were asked to rate the amount of pain we felt on a scale of 0-100. Here our highest rating was a 20.  Throughout the procedure we were repeatedly reminded that we could stop at any time by saying “stop”. During the trials, investigators also monitored pulse rate, galvanic skin response and facial expressions as nonverbal measures.

The first phase of this work will focus on adults with autism. Participants are required to have an IQ above 80 and to personally consent to participation. In addition, participants must successfully complete a quiz to show that they fully understand the consent process and their rights as participants, including the right to change their mind and withdraw consent at any time.  In addition, two adults with autism will serve as consultants to the scientists conducting the study; one is a member of the faculty at the Vanderbilt School of Music and the other is a Vanderbilt MD-PhD student.


Alison Singer and Alycia Halladay unscathed after experiencing the study.

Based on our first-hand experience, we both feel very comfortable encouraging adults with and without autism to participate in this important study, as long as they are capable of consenting.  Participants will feel some pain, but it is short and not difficult to experience. In fact, I experienced more heat-based pain on the plane ride home when my laptop overheated on my legs. All of the members of this research team are actively engaged and very focused on making sure participants do not experience any more discomfort than is necessary.  If the pain response were not altered in people with autism, then this sort of research would not be necessary.  In order to make sure that individuals with autism are not unnecessarily feeling pain that could otherwise be treated, this type of project is needed.

For more information about this study, visit the Cascio Lab website.

170330_2728_barnettI have been so proud to work with the Autism Science Foundation since it was launched in 2009. As an adult with autism, I think it’s very important to support research, because research will give us important answers about what causes autism and how best to provide support to people with autism.

That’s why I am so excited to be involved with Wall Street Rides FARFor Autism Research.

On Saturday, October 7th the autism and Wall Street communities will come together for this annual bike ride that is truly for everyone. With four scenic options to choose from (4, 20, 30 or 62 miles), there is a route for you whether you are a seasoned cyclist or a recreational weekend rider like me. The family-friendly 4-mile route (with an 8-mile option) makes it possible for younger children to ride, including children with autism.

As many of you know, my family and I have been raising money for autism research for many years. We are proud to support ASF because we know the funds we raise will support the most cutting-edge, important research that will make real changes in people’s lives. For example, the Autism Science Foundation sponsors the Autism Sisters Project, which is trying to learn about why more males than females are diagnosed with autism. My sister Sabrina, my brothers and I are all participating in this study. If we can understand why girls seem to have protection against autism we can use that information to help both boys and girls.

I will help kick off the ride this year as a speaker at the Rooftop Kick-Off Party on Wednesday, June 21st at Rare View in Chelsea. I hope you can join me and my family there! In addition to a great time, you will get a chance to learn more about the research being funded by ASF and get details on the Ride! I hope to see you there!

To learn more about these events and to RSVP for the kickoff party, visit wallstreetridesfar.org. It’s full of information on the Ride and is the best place to register and get up to date on the latest events.

I hope to see you at the ride!

By Dr. Alycia Halladay, Chief Science Officer of the Autism Science Foundation

This was my third year attending Scoring Goals for Autism in Wayne, Pennsylvania, and it’s amazing to see the growth, expansion and yet consistency in the program.  What I mean by “consistency” is the volunteers are gracious and friendly, the participants come from all ends of the spectrum, and it is a moving experience for anyone who participates. Some people I recognized from years before and some were newer, but all of them were smiling when they walked in and smiling when they left.

Except one.

My daughter Sarah who is on the autism spectrum has been going to Scoring Goals for Autism as long as I have, and we always look forward to the event.  As a result of the program last year, she decided she wanted to join our local instructional, recreational soccer league for six-year-olds.  I signed her up reluctantly, but the past few seasons have been uneventful and Sarah was really getting the hang of playing.  Unfortunately that stopped on Thursday.  She got in a little bit of a tussle with another player, who she has known for two years.  Sarah apologized to her (begrudgingly, but an apology is an apology), and after the practice I apoloDSC_0227gized to her mother and thought the whole issue had been settled amongst the parents.  However, on Friday I got a call from the coaching staff to tell me that as a result of the altercation, the parents of the other girl were concerned about Sarah’s future participation because of her aggressiveness.  This is a pretty typical story even in 2017.  Later on Friday, when I went to pick Sarah up, this girl and some other kids were yelling at Sarah for what had happened, with Sarah’s head buried in her chest.  So when we showed up for the event on Saturday, Sarah was in no mood whatsoever for soccer.  Here is a picture at the start of the day.

DSC_0223Sarah’s volunteer buddy, Kelly, was absolutely amazing.  Even though it was a hot day and the air conditioner could not keep up, she had Sarah running around, talking, and interacting with other kids.  When another little girl knocked down her tower, I thought there would be a scene.  But she looked at Kelly and said, “that’s okay.”  By watching other kids playing games in such a loving, non-competitive environment, all for fun, it became okay for her to just love kicking the ball around with other kids.

DSC_0202 copyBy the end of the day, after drills, games, knocking down towers and bowling pins, kicking balls into the goal, and even having the chance to help other get through the same routines, her mood lifted and she told me she wanted to go back to soccer practice to try it again.  The point of her being on a soccer team is not to become the next Mia Hamm.  The goal is to allow her to develop social skills, get to read emotional cues, and most importantly, share the joys of playing sports with other kids her age.  And yes, to learn to understand and regulate her emotions appropriately.

2017-04-29_14-02-21_835Scoring Goals for Autism isn’t just about soccer.  The inspiration for the program, Tommy Bak, loves to play soccer, but the program exists to allow people of all disabilities to play sports in a nonjudgmental, supportive, safe environment with other people of differing abilities.  Here is Sarah at the end of the day, looking forward to next year.  There were a lot of Sarahs there that day, maybe not just like Sarah, but in the same boat.  Thank you so much to Scoring Goals for Autism, especially the Bak Family,  who is able to reach people with autism through this important event.

By Alycia Halladay, PhD


Alycia Halladay, PhD, Chief Science Officer, Autism Science Foundation

This article appeared in the journal of the Aspergers and High Functioning Autism Association of New York, or AHA, called On the Spectrum. They have graciously allowed us to reprint it.


The slogan for the Autism BrainNet is: “It takes brains to understand autism.” Yes, it takes the brains of scientists, researchers and clinicians to work with families and people affected to understand the challenges of autism. But it also takes more than that. Scientists need to actually study the brains of people with autism to truly understand how this miraculous organ controls so many different behaviors that, when together, are an autism spectrum disorder.

The Autism BrainNet was launched in 2014 and was previously known as the Autism Tissue Program, which was crucial in helping researchers understand the types of cells that were affected, where they were affected, and how they were affected. The first 15 years were critical to collect and distribute enough tissue to establish what is known and acknowledged as features of the brains of people with autism. This includes: neurons not going to the right places when they are being formed during development, too few of one type of neuron in some parts of the brain, and evidence that factors like the immune system play a role in how neurons in the brain are shaped. Now, in the next phase, the Autism BrainNet scientists and researchers are aggressively conducting experiments to use these findings to develop new treatments and improve existing interventions to help those with autism.

For example, researchers have known that a chemical called GABA in the brain is
important in autism. They just discovered that the number of traffic directing neurons, called “interneurons,” that help connect different neurons are reduced. These interneurons use GABA to turn off neurons. This is the fine-tuning of brain activity that may affect sensory input. If neurons are not turned off, too many neurons are turned on. It could explain why some people with autism feel overwhelmed with information. Also, researchers are able to better understand the role of a brain area called the amygdala. This area is involved with brain circuits that control fear and anxiety, so it is important in autism spectrum disorder. Future interventions that target this area could help these behaviors and improve social interaction. Finally, people with autism may have too many brain connections: not just fewer neurons that turn off other neurons, but also more spots on each neuron where they connect. These findings fit in with the larger picture of brain areas not being properly connected, or the “functional underconnectivity hypothesis.” Replicating this in an animal model has given hope to advance the study of different compounds that can ITB-ABN_Registration Card_5x7_Everson Family_NOT FOR PRINTING_Page_1.pngchange this effect on neurons and improve behaviors.

This just shows you: without knowing about the brains of people with autism, scientists will never understand the brains of people with autism.

The Autism Treatment Network has recently joined forces with the Autism BrainNet to ensure even more people know the importance of this resource and get information about participating in the program. The ATN is a collection of 14 research sites across North America that share evidence based guidelines for assessment and management of medical issues related to autism like gastrointestinal, dietary and neurological issues. Also, Autism BrainNet information is now included in many California Regional Center DDS offices.

To get more information, click here. By registering on this website, you are not obligating yourself to do anything more than learn more. Thank you to all the families who have already signed up – it truly makes a difference.

A summary of autism discoveries in 2016 and what they mean for families

By Alycia Halladay, PhD, Chief Science Officer of the Autism Science Foundation and the Scientific Advisory Board of the Autism Science Foundation

year-end-summary-podcast-logoTo listen to our year-end research summary podcast, click here.

For decades, the autism community has known that autism affects the entire family. Biological parents have been included in autism studies to examine where genetic mutations come from, but always with an eye for understanding the affected individual. This year in research saw a much bigger focus on family members of those with autism, particularly siblings.  The goal of these studies is to understand the genetic and biological nature of autism so that help can be provided not just to those with a diagnosis, but to family members as well.

Many studies focused on what is known as the “broader autism phenotype,” previously explored in biological parents. The “broader autism phenotype” refers to some behavioral features of autism, including those in emotion, language, and social skills that do not meet the level of a diagnosis of autism spectrum disorder. Rather, they have been termed anything from “intermediate” autism to “a hint of autism.” Joe Piven and James Harris hypothesized this year that Bruno Bettleheim may have tragically misinterpreted these features, in the absence of a true understanding of autism, as “refrigerator mothers.” Clinicians have urged scientists to note these symptoms in a way that does not create a new diagnostic category and noting certain social, personality and language characteristics in family members has been crucial for nailing down the underlying biology.

Importantly, significant scientific discoveries in autism were made possible by looking directly at the brains of people with autism. This type of research has been made possible through the Autism BrainNet. This summary highlights the important role of studying brain tissue from individuals with autism to better understand people with autism across the lifespan, including those with known causes and unknown causes of autism spectrum disorder (ASD). See the section below entitled “Using brain tissue to understand causes of ASD” for more details on findings from brain tissue research in 2016.

Siblings show features of autism, but not to worry

This year, four studies assessed the broader autism phenotype in siblings, and other studies went further to look at psychiatric symptoms in siblings who were not diagnosed with autism. In the past, researchers mistakenly believed that siblings showed no symptoms of autism. In fact, adolescent, school age, and adult siblings of those with autism show elevated autism symptoms [1, 2] as well as categorical features of autism similar to those seen with autism [3], compared to those with no family history. High-risk infant sibling studies have shown that siblings of toddlers with autism, while not diagnosed with autism, have a higher rate of autism spectrum disorder (ASD) symptoms [4].

screen-shot-2016-12-06-at-1-35-38-pmThis is also consistent with the broader autism phenotype, with the last study indicating that sibling symptoms are observed across the lifespan. Unfortunately, signs of the broader autism phenotype puts siblings at risk for internalizing and externalizing behaviors like depression, psychological problems, and other behavioral issues [5, 6]. In addition to anxiety and depression, research this year showed increased risk of psychiatric comorbidities including ADHD and substance abuse disorders [7-9]. On the other hand, siblings who were within the typical range of Social Responsiveness Scale (SRS) scores didn’t show elevated sensory issues [10]. The goal of studying siblings of those with autism, again, is not to look for features which pathologize them, but to help identify features, challenges, and strengths that help them. Research published previously identifies the unique nature of sibling relationships, in that siblings of a person with autism view their relationship positively across the lifespan, whereas siblings of typically developing individuals tend to report positive feelings at a decreased rate in adulthood [11].

Understanding the causes of autism by studying sex differences

In addition to understanding siblings to help develop specialized services and supports, learning about siblings can help researchers understand the causes of autism and, specifically, why females are less likely to be diagnosed compared to males. New prevalence data from the CDC showed that the prevalence of autism is again at 1:68, perhaps showing a plateau in the rates of autism in the US. However, the difference in the rates between males and females still hovers around 4:1 depending on IQ [12]. Researchers this year showed that females may be able to hide symptoms because of better social abilities [13] and because they may be protected in some way from certain symptoms [14]. For example, those studying infants at risk for autism show that baby girls with autism show increased attention to social stimuli compared to baby boys [15]. This difference may ASF_AutismSistersProject_Logosaffect how they express symptoms later on. Finally, preliminary studies this year suggest a slight bias in diagnostic instruments [16] and evidence of camouflaging autism symptoms in females [17].

There are likely multiple reasons behind the male sex bias in autism, but few have received any empirical study. This year, the Autism Sisters Project began recruiting at the Icahn School of Medicine at Mount Sinai. This study is poised to understand why females are not diagnosed as often, including differences in IQ and underlying genetic factors. Of importance, the study is focusing on the undiagnosed sister of individuals with ASD. As much as studying siblings with autism may help researchers understand sex differences in autism, so will actually studying males and females with ASD. Donna Werling from USCF looked at genes expressed in the brains of males and females with and without autism to understand sex differences in gene expression, particularly in those genes associated with autism. She found that it was not ASD risk genes that show differences, but those that are involved in neural pathways associated temple-grandin-quotewith autism, like microglia and the immune system, that show sex differences. The male bias in this gene expression may be what modulates ASD risk [18]. A male sex bias is not unusual across neurodevelopmental disorders, and so understanding its role in autism diagnoses may be informative of disorders like ADHD and anxiety as well. Just like there are fewer females diagnosed with autism, there are fewer brains of females to study, slowing scientists’ understanding of ASD. In order to learn more about how women with ASD can participate, click here.

More to learn about genetics associated with ASD

Even more new risk genes were discovered this year, and/or replicated in different cohorts. These investigations went beyond “autism” vs. “no autism” to specific features of autism, with the goal of understanding what genes lead to what behavioral features of ASD. For example, several studies found associations between a gene called POGZ and autism, particularly autism with intellectual disability [19-23]. POGZ is a gene that makes a protein that affects the expression of other genes. Therefore, the mutation of this gene produces disruption in the expression of several genes, rather than just one. Similar 178352-376x250-genetic-factorsspecific behavioral features are found with mutations of TRIP12 or DYRK1A, which also leads to widespread, rather than specific, changes in gene expression with a particular form of autism: autism with intellectual disability [24, 25]. By further investigating individuals for whom substantial amounts of data is available, including cognitive ability and comorbid medical conditions, the causes of these features will be better understood and will hopefully lead to better treatments. Researchers have also better identified how genes seen in other disorders but cause autism are transmitted, for example via maternal [26, 27] or paternal [28] pathways, influenced by things like paternal age [29], which might aid genetic counseling. Contrary to this idea, however, is the finding that individuals with either a known genetic cause of autism or autism where there is no known cause (i.e., idiopathic) have a considerable amount of overlap in mutations in the brain which affect how genes are turned on and off – in other words “epimutations” [29, 30]. This is further evidence that beyond the way DNA is sequenced, factors that affect how genes are activated are important to autism etiology as well. Epigenetic markers are known to be sensitive to environmental exposures of different types and insight into these pathways continue to open the door to understanding gene/environment interactions in autism. 

d94f58a75e518827151847b95d757e1fAnd it’s not just about pure genetics, it’s about interactions between genes and the environment.

Genetics plays a huge role in the causes of autism, but this year researchers dove even deeper into the multifactorial causes of autism, specifically the role of genetics and the environment. The environment includes, broadly speaking, anything from toxic chemicals to age of the parent. It includes sociological, pharmacological, toxicological, and medical exposures.

This year saw two epidemiological studies examining the interaction between genes and the environment, but this time the investigation expanded to include who carried the genetic mutation and how autism was defined. First, studying the genotype of mothers showed that a particular mutation of the serotonin receptor gene and a high level of stressors during pregnancy produced a higher risk for having a child with autism than those without this same mutation [31]. Rather than using these factors to understand autism risk, others are going beyond to understand symptoms within autism. For example, using the Simons Simplex Collection, scientists showed that boys with autism who had genetic markers of mutations called copy number variations, together with exposure to an environmental exposure, showed the most severe autism symptoms, marked by repetitive behaviors and cognitive challenges [32]. The study is the first to look at type and severity of symptoms following multiple risk factors rather than a diagnosis, and the idea of understanding multiple risk factors for symptoms, rather than diagnosis itself, needs further study. Animal models of autism found that paternal age, a commonly accepted risk factor for autism spectrum disorder, combined with a mutation of a gene that affects synaptic development, results in certain symptoms of ASD in this model [33]. More fine-grained analysis of autism symptoms, rather than an autism diagnosis per-se, is needed to better understand the causes of autism. It’s also important to understand environmental factors because in some cases, like those of chemical and toxicological exposures, these can be controlled through regulatory means. Many studies have linked air pollution to autism [34] and in early July a landmark consensus statement authored by over 30 scientists, physicians, and public health experts was published which calls for the reduction of toxic chemical exposures to possibly reduce the risk of many developmental disorders [35]. So far, the only established way to protect against autism has been dietary folic acid supplementation [36], so reduction of modifiable risk factors should be a focus of future public health research.

Another potentially modifiable risk factor is maternal infection during pregnancy. Of course, not all cases of maternal infection are preventable, but some of them are. This year, a study revealed that neither having the flu, nor being vaccinated against the flu during pregnancy, was shown to contribute to autism risk in children [37]. However, maternal immune response during pregnancy was linked to a specific behavioral phenotype of autism, specifically those with intellectual disabilities [38]. According to animal models, the effects of altering the immune system function early in cell formation may lead to longer lasting elevations in chemokines (which are immune chemicals associated with autism) than previously thought [39]. This may be attributed to long lasting changes in gene expression patterns, regulated via epigenetic mechanisms [40, 41], resulting in an increase of methylation of genes and producing effects across generations. These findings converge with other research that demonstrates similar methylation patterns in individuals with ASD, even without immune system challenges during early life.

For years, some autism researchers have observed the presence of antibodies to brain tissue in some mothers of children with autism. This year, researchers looking at animal models discovered that they may be acting through an autism risk gene [42]. Also, the increased risk may be particularly elevated in mothers with specific medical conditions [43]. While scientists remain cautious about translating these findings to a commercialized method of determining autism risk, they continue to provide insights into the neurobiology of autism, and especially the immune system.

Using brain tissue to understand causes of ASD

Brain tissue research will also help researchers better identify causes of different types oITBf autism so that better treatments can be developed. For example, one of the more challenging and debilitating medical comorbidities associated with autism is seizures and epilepsy. A study of brains of individuals with both autism and autism and epilepsy show increased numbers of glial cells. These cells are not neurons, rather they provide support and protection to brain cells [44]. The glial cell numbers were highest in those with restricted and repetitive behaviors, but, interestingly enough, the number of glia go down over time in individuals with autism, but up in those without autism. This suggests that the glial cells contribute to autism severity and cause. Similar comparisons to other disorders associated with autism were made studying amyloid B precursor protein and their metabolites. These molecules are associated with Alzheimer’s disease but also have a host of other functions that are not pathogenic. For example, they can affect neuroinflammation and normal cellular activity. In autism, levels of these proteins were reduced in brain and plasma, but elevated in individuals with Fragile X syndrome [45]. This suggests that these amyloid B proteins are involved with both disorders, and may be a target of interventions in the future.


Figure found in Parikshak et al., 2016

Brain tissue research goes beyond identifying treatment targets to helping researchers understand how the brains of people with autism work on a cellular level. This year, two studies demonstrated that in addition to mutations in autism risk genes, mutations in areas of the gene that control the function of autism risk genes are also affected [30, 46]. What is also interesting is that regardless of the symptoms or causes of autism, the pattern of gene activity was similar in those with autism, validating a much smaller study from years ago [46]. These results also reiterate the importance of early intervention for treatment of debilitating autism symptoms, since both genes identified recently that control brain development peak during the first few years of life. It is important for all families, regardless of whether or not they are directly affected by autism, to learn more about brain tissue donation. You can register for more information by clicking here.


Should clinicians think in terms of autism diagnosis, or in terms of symptoms?

This year showed the shared features between autism and many other disorders like Phelan-McDermid syndrome, mutations of chromosome 16, Dup15, and even schizophrenia. In particular, disorders don’t just share autism symptoms; they show similar neurological and cognitive features as well [27, 47]. So how much is specific to autism, and how much is related to behavioral, neurological, and other medical issues that are seen without an autism diagnosis? And do these genetic findings explain certain symptoms associated with autism, but not core to autism? It has been argued that classifying individuals based on specific symptom dimensions, such as the presence of abnormal behaviors, absence of other behaviors, and cognitive ability may help clinicians better distinguish cross disorders [48, 49]. This idea is not new, with a recent movement towards a new way of thinking towards autism diagnosis [50]. New findings from the brains of individuals with a diagnosis of autism or schizophrenia show significant overlap between the gene transcription in the brains of people with either autism or schizophrenia, but not bipolar disorder [51]. The authors conclude that these two disorders share many genes associated with synapse development, and the formation of connections across different brain regions. Therefore, these disorders may not be totally different at the biological level. Rather than thinking of autism as a whole, early signs of autism can also be linked to specific genetic markers, which may explain autism symptoms, but not autism as a diagnosis. This includes mutations of the oxytocin receptor on later empathy [52] and dopamine receptors on a core feature – initiating joint attention [53]. This idea has enormous implications for autism research and treatment, as it implies a switch in the way autism is identified. It has been suggested that behavioral symptoms, combined with biological and environmental variables, should be combined to lead to inselcuthbertgraphiccategories, rather than diagnosis of disorders. This is called Research Domain Criteria, or RDOC.

Autism can also be very difficult to diagnose, but this year two new studies suggested that the process can be streamlined, at least a little bit. In school age verbal children, a new instrument called the Autism Symptom Inventory (ASI) was good at diagnosing autism in about 20 minutes [54]. Another instrument, which doesn’t have a name yet, combines three short instruments (including the ASI) and was also promising, especially in terms of studies aiming to understand the causes of autism, both genetic and environmental [55]. These studies offer hope to large scale epidemiological studies seeking to identify and characterize individuals with autism, although right now their ability to identify different subtypes which may be amenable to specialized treatments is limited.

When it comes to intervention, earlier is best, but not the only option

The most remarkable evidence of the effectiveness of early intervention has come from pactlongitudinal studies – those that study an intervention YEARS after it was delivered. If early intervention improves brain connectivity and allows for connections to be formed to alleviate autism symptoms, the effects may not be seen right away – it may take years. They can take the form of an intervention study that follows families for a long time, or by investigating factors early on that predicted improvement at school age and beyond. This year saw both. In 2010, a gold standard randomized clinical trial study out of the UK looked at a parent-delivered intervention focusing on communication, and, while they found it showed promise, it didn’t produce improvements in symptom severity [56]. The initial findings were hopeful, but also disappointing. However, when they followed up on these children five years later, the training of the parents to deliver the intervention resulted in a reduction of autism symptoms [57]. The findings are important for many reasons. First, autism intervention is a journey, not necessarily a destination, and interventions delivered early on may alter the trajectory of symptoms [57]. Second, parents can deliver interventions in a wide variety of settings in a way that is more intensive than limited clinic time, and an intervention targeted at one set of autism symptoms like social communication may also affect others like repetitive behaviors [58]. This does not mean that trained Applied Behavioral Analysis (ABA) therapists and intervention delivered by trained professionals should be abandoned. Parent-delivered interventions are a supplement at ages when kids spend most of their time with parents rather than schools. Another important thing to remember about early intervention is that more data published this year shows that for a percentage of children, a diagnosis is not possible at two years of age. A group of children who show some symptoms but don’t meet criteria at two years of age do end up with a diagnosis by three years of age [59] despite being seen by well-trained, very experienced clinicians. Early intervention may help those who don’t have an actual autism diagnosis yet. Studying infants with autism has also been instrumental in determining not only interventions, but the nature of autism itself. For years, people assumed that the reduced eye contact in people with autism was because they were actively averting the eyes, found eye contact aversive, and didn’t want to look at the gaze of the other person. However, this isn’t the case. At least early in life, infants with autism don’t actively avert gaze, they just aren’t that interested in looking at the eyes and don’t get the same social signals from eye contact as those with autism do [60].

Parents as methods of treatment delivery

Parent-delivered interventions can be used at different times, again to supplement, rather than replace, other treatments delivered in clinical settings. Parent training, not the less intensive parent education, on behavior management techniques improved adaptive behavior and daily living in children with autism. However, these gains were mostly seen in those with average intellectual functioning [61]. This suggests that not all individuals respond to parent-delivered interventions. And it isn’t just used in isolation. It enhances the efficacy of drugs to alleviate ADHD in those with autism [62]. Parent training may seem like an easy solution, but in the real world setting of parents and trainers, it is very complicated [63].

What can predict who will respond to what treatment?

There have also been advances in pharmacological treatments of autism, but they always struggle with improving behavior or outcome, not specific to core autism symptoms. Oxytocin, a naturally occurring hormone, has shown mixed results in improving different aspects of autism-related behavior, including face recognition, social behavior, and empathy [64]. Looking at the effect of oxytocin on the brain, it improves connectivity between areas of the brain involved in reward and those involved in perception of social communication cues in children with autism [65]. However, it isn’t simple, and, as it turns out, that makes the story more promising. People with mutations of the oxytocin receptor have different types of mutations. These different types of mutations in people with autism lead to different patterns of this connectivity [66] as well as the ability to recognize faces [67]. Finally, these different mutations also predict the behavioral response to oxytocin – in other words, whether or not this hormone produces improvements in social abilities [68]. These different studies are a perfect illustration of how personalized medicine will improve autism treatment. Those with particular types of genetic differences will respond better to oxytocin treatment than others, which will speed up people receiving the right type of intervention.

tp-r3-figure3In addition to genetic markers predicting treatment response, advances in other biomarkers to predict treatment response have been made as well. Individuals who were more responsive to Pivotal Response Treatment (PRT) showed a specific pattern of pre-treatment brain activity when presented with a social situation on a video [69]. In fact, it predicted response to treatment better than any baseline behavioral measures. In the future, just like looking at the genetic makeup of people with autism, understanding their underlying brain function before treatment can help get the people into the treatments that would benefit them the most.

The whole purpose of improvements in autism diagnosis and interventions is to deliver services to individuals that need them. So, how are insurance mandates doing in terms of identifying individuals with autism and providing them with the treatments they need? This year, David Mandell at the University of Pennsylvania demonstrated with data obtained through insurance companies that these mandates are increasing the number of people receiving services. That’s the good news. The bad news is that the increase is not nearly as much as it should be keeping in pace with the prevalence of autism. So, he concludes, these mandates are necessary but not sufficient to provide services to all that need them [70]. In addition, there are acknowledged gaps in what pediatricians know about non-medical treatments and services in their areas, and what parents need them to understand [71].

In summary, this year saw research that helps understand the causes of autism; includes siblings to provide better services to the entire family; showed promise of the concept of “personalized medicine” everyone has heard so much about; demonstrated the long term, not just short term effects of behavioral interventions and the importance of parents and caregivers; and emphasized the need to better understand features of individuals with autism rather than just the straight diagnosis of ASD.


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