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Keyword: ‘epigenetics’

What is epigenetics, and what does it have to do with autism?

January 20, 2012 11 comments

This week’sGot Questions?” answer comes from Alycia Halladay, PhD, Autism Speaks director of research for environmental sciences

If you’ve been following autism research in recent years, you have probably read—many times—that familial, or inherited, risk is seldom the whole picture. A few inherited genes are sufficient by themselves to cause autism. But most so-called “autism genes” only increase the risk that an infant will go on to develop this developmental disorder. As is the case in many complex diseases, it appears that autism often results from a combination of genetic susceptibility and environmental triggers.

This is where epigenetics comes in. Epigenetics is the study of the factors that control gene expression, and this control is mediated by chemicals that surround a gene’s DNA. Environmental epigenetics looks at how outside influences modify these epigenetic chemicals, or “markers,” and so affect genetic activity.

It is important to remember that scientists use the term “environment” to refer to much more than pollutants and other chemical exposures. Researchers use this term to refer to pretty much any influence beyond genetic mutation. Parental age at time of conception, for example, is an environmental influence associated with increased risk of autism, as are birth complications that involve oxygen deprivation to an infant’s brain.

Because epigenetics gives us a way to look at the interaction between genes and environment, it holds great potential for identifying ways to prevent or reduce the risk of autism. It may also help us develop medicines and other interventions that can target disabling symptoms. We have written about epigenetics previously on this blog (here and here). So in this answer, I’d like to focus on the progress reported at a recent meeting hosted by Autism Speaks.

The Environmental Epigenetics of Autism Spectrum Disorders symposium, held in Washington, D.C. on Dec. 8, was the first of its kind. The meeting brought together more than 30 leaders in autism neurobiology, genetics and epidemiology with investigators in the epigenetics of other complex disorders to promote cross-disciplinary collaborations and identify opportunities for future studies.

Rob Waterland, of Baylor College of Medicine in Texas, described epidemiological studies and animal research that suggested how maternal nutrition during pregnancy can affect epigenetic markers in the brain cells of offspring.

Julie Herbstman, of Columbia University, described research that associated epigenetic changes in umbilical cord blood with a mother’s exposure to air pollutants known as polycyclic aromatic hydrocarbons (PAHs). PAHs are already infamous for their association with cancer and heart disease.

Rosanna Weksberg, of the Hospital for Sick Kids in Toronto, discussed findings that suggest how assisted reproductive technology may lead to changes in epigenetically regulated gene expression. This was of particular interest because assisted reproduction has been associated with ASD. Taking this one step further, Michael Skinner, of Washington State University, discussed “transgenerational epigenetic disease” and described research suggesting that exposures during pregnancy produce epigenetic changes that are then inherited through subsequent generations.

Arthur Beaudet, of Baylor College of Medicine, discussed a gene mutation that controls availability of the amino acid carnitine. This genetic mutation has been found to be more prevalent among children with ASD than among non-affected children, suggesting that it might be related to some subtypes of autism. Further study is needed to follow up on the suggestion that dietary supplementation of carnitine might help individuals with ASD who have this mutation. Caution is needed, however. As Laura Schaevitz, of Tufts University in Massachusetts, pointed out, studies with animal models of autism suggest that dietary supplementation may produce only temporary improvements in symptoms of neurodevelopmental disorders.

So what does this all mean for research that aims to help those currently struggling with autism? The meeting participants agreed that the role of epigenetics in ASD holds great promise but remains understudied and insufficiently understood. For clearer answers, they called for more research examining epigenetic changes in brain tissues. This type of research depends on bequeathed postmortem brain tissue, and Autism Speaks Autism Tissue Program is one of the field’s most important repositories. (Find more information on becoming an ATP family here).

The field also needs large epidemiological studies looking at epigenetic markers in blood samples taken over the course of a lifetime. One such study is the Early Autism Risk Longitudinal Investigation (EARLI). More information on participating in EARLI can be found here.

Autism Speaks remains committed to supporting and guiding environmental epigenetics as a highly important area of research.  We look forward to reporting further results in the coming year and years.

Got more questions? Send them to gotquestions@autismspeaks.org.

Read more autism research news and perspective on the science page.


What is epigenetics? Does this new field hold promise for understanding the causes of ASD?

November 19, 2010 9 comments

“Got Questions?” is a new weekly feature on our blog to address the desire for scientific understanding in our community.  We received over 3000 responses when we asked what science questions were on your mind. We answered a few here and the Autism Speaks Science staff will address the other themes we received in this weekly post.

Scientists have long wondered how experiences during a person’s lifetime can alter behavior and body functioning.  In the early 1800’s Jean Batiste Lamarck suggested that giraffes’ necks grew long through many generations of stretching to reach distant leaves.  That theory eventually fell to evolution–pressures from the environment selectively amplify or quiet certain traits that are variably present within a population. Later, the DNA code was found to be the mechanism for inheritance and the level at which selective pressure acts.

Today’s scientists see hints of Lamark as they peer into the molecular biology of inheritance.

Consider DNA to be a library of books that encode genes. These “genetic books” must be read so that proteins can be formed from the code.  Some genetic books are open and available for reading by the cell’s molecular machinery.  Others maybe temporarily unavailable and still others are in the restricted section—essentially permanently unreadable.

Experiences throughout an individual’s life create tags on the genetic code, marking it as available or not for reading. The molecular methods that control the availability of the genetic code are collectively referred to as epigenetic mechanisms. Literally meaning “above the genome”, epigenetic mechanisms tag DNA with different chemical marks, such as methyl or acetyl groups.  Certain tags can increase the reading frequency, resulting in more protein building-blocks transcribed from the DNA code, and more of that gene “expressed”.  Other tags result in a particular piece of the genetic code to be skipped during reading.

A host of environmental agents and interactions may leave epigenetic marks on the genome.  Early life stress, smoking, exposure to toxins may all leave epigenetic marks either creating or removing barriers for protein creation.

Here is where Lamark comes in.  Most epigenetic marks are removed before the sperm and egg meet to form an embryo, but sometimes, epigenetic marks remain.  This is one mechanism by which environmental exposures can be passed along from parent to child.

The study of epigenetics and gene expression in autism is underway and early findings are exciting.  Some of the genetic syndromes associated with autism, such as Angelman and Prader-Willi syndrome, result from epigenetic marks that render one parent’s genetic contributions unreadable.  Recently, gene expression studies from the blood and even brain tissue of individuals with autism have shown differences in the activity of patterns of genes that are involved in brain development and function.

This is an exciting area of research and we look forward to sharing more details as we learn more from the science.

Read more about epigenetics on or blog.

Beyond genetics: What the new fields of functional genomics and epigenetics are revealing about autism

April 22, 2010 9 comments

Today’s guest post comes to us from Valerie W. Hu, Ph.D. Dr. Valerie Hu is a Professor of Biochemistry and Molecular Biology at The George Washington University Medical Center as well as a mother of a son with ASD.  She redirected her research focus towards autism about 5 years ago and has since published 6 papers on the genes and biological pathways associated with ASD.  Dr. Hu received her Ph.D. in Chemistry from Caltech and did her postdoctoral research in Membrane Biochemistry and Immunology at UCLA.  More information about her research and papers can be obtained at:  http://www.gwumc.edu/biochem/faculty_vhu.html

For many years, genetics has followed the traditional approach to identifying genes associated with various disorders, including autism.  However, the wide diversity of symptoms and behaviors associated with autism spectrum disorders (ASD) has posed a significant challenge to identifying mutations in one or a few genes that are reliably associated with ASD.  More recent attention has focused on copy number variants (CNVs) which are submicroscopic regions of chromosomes that have been found to be lost or duplicated in some individuals with ASD. Together, these studies are making progress in identifying a number of genes that function at the synapse between nerve cells. Nevertheless, the combination of all known genetic mutations still does not account for the majority of autism cases or for the association of non-neurological symptoms observed in autistic individuals.

My laboratory at The George Washington University Medical Center has taken a functional genomics approach to studying genes that may be deregulated in autism.  Rather than identify mutations in DNA, our goal has been to identify genes whose activity, as indicated by gene expression level, is altered in order to identify dysfunctional biochemical pathways and impaired cellular functions in autism.  Thus, using a method known as DNA microarray analysis to profile gene expression in cells from identical twin pairs who are differentially diagnosed with autism (one autistic, the other not reaching the threshold for an autism diagnosis), sibling pairs where only one sibling is autistic, and unrelated case-controls, we identified many genes whose expression levels (activities) are different from non-autistic individuals.  Furthermore, by subtyping the unrelated autistic individuals according to symptomatic severity across over 63 symptoms probed by a commonly used diagnostic assessment instrument (Autism Diagnostic Interview-Revised), we were able to identify gene “signatures” for each of 3 ASD subtypes studied.  These signatures not only revealed genes unique to a given subtype of autism, but also overlapping genes that presumably control common symptoms of autism across subtypes.  Interestingly, a set of genes that regulate the biological clock (that is, circadian rhythm) were found to be disrupted only in the subtype of ASD exhibiting severe language impairment.

These studies demonstrating different gene expression signatures between identical but differentially diagnosed twins as well as revealing differential expression of hundreds to thousands genes depending on ASD subtype suggest the involvement of  “master switches” (or epigenetic mechanisms) in the control of gene expression.  Two new studies by our laboratory, published in two different journals on Apr. 7, 2010, suggest that epigenetics may play a significant role in the regulation of gene expression in autism (read a blog from AS staff on epigenetics).  In one study, published in the FASEB Journal, we identified chemical tags (called “methyl groups”) on the DNA of individuals with autism that led to gene silencing. This mode of turning off a gene is potentially reversible with the proper drugs if the specific gene can be properly targeted.  The second study, which was published in the journal Genome Medicine, reports on the differential expression of microRNA in autism.  MicroRNA are recently discovered snippets of RNA (ribonucleic acid), each of which can inhibit the expression (and thus activity) of hundreds of genes.  The effects of microRNA are also reversible by treatment with complementary “anti-sense” RNA.  While methylation inhibits gene expression at the level of DNA, microRNA inhibits at the level of RNA.  These two studies together illustrate two different “epigenetic” mechanisms controlling gene activity in autism that lie beyond genetic mutations.

In the study published in the FASEB Journal, we again used cell lines derived from identical twins and sibling pairs in which only one of the twins or siblings was diagnosed with autism to identify chemical changes on DNA. We then compared the genes that showed changes in DNA tagging (methylation) with a list of genes that showed different levels of expression from these same individuals. The amounts of protein produced by two of the genes that appear on both lists were then investigated in brain tissues from the cerebellum and frontal cortex of autistic and control subjects which were obtained through the Autism Tissue Program.  We found that both selected proteins, RORA (retinoic acid-related orphan receptor-alpha) and BCL-2, as predicted by the observed increase in methylation, were reduced in the autistic brain.  Although BCL-2 has previously been reported to be reduced in autistic brain, RORA is a novel gene which is relevant to many of the observed deficits in autism.  Specifically, RORA is involved in several key processes negatively affect by autism, including Purkinje cell differentiation, cerebellar development, protection of neurons against oxidative stress, suppression of inflammation, and regulation of circadian rhythm.

These results suggest that blocking the chemical tagging of these genes may reverse some symptoms of autism if targeted removal of methyl groups from specific genes can be accomplished.  Furthermore, this study, which links molecular alterations in blood-derived cells to brain pathobiology, demonstrates the feasibility of using more easily accessible cells from blood (or other non-brain tissues) for diagnostic screening.

This research is reported in the study, titled “Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain,” which was recently published in the Federation of American Societies for Experimental Biology (FASEB) Journal, and is available online at: http://www.fasebj.org.

In the study published in Genome Medicine, we identified changes in the profile of microRNAs between twins and sibling pairs, again discordant for diagnosis of autism.  We discovered that, despite using cells derived originally from blood, brain-specific and brain-related microRNAs were found to be differentially expressed in the autistic samples, and that these microRNAs could potentially regulate genes that control many processes known to be disrupted in autism.  For example, differentially expressed miRNAs were found to target genes highly involved in neurological functions and disorders in addition to genes involved in gastrointestinal diseases, circadian rhythm signaling, and steroid hormone metabolism. The study further shows that by treating the cells with antisense RNA antagonists (inhibitors) to specific microRNA or by employing mimics of a particular microRNA, one can reverse the pattern of expression of a given target gene regulated by that microRNA.

This study, titled “Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines” was highlighted as an “Editor’s pick” in the journal Genome Medicine.  It is available online at: http://genomemedicine.com/content/2/4/23.

By integrating both DNA methylation and miRNA expression studies with gene expression data, Dr. Hu and colleagues are applying a systems biology approach to understanding this complex disorder.

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Thank You for Supporting our Pioneering Research

January 10, 2012 8 comments

Guest post by epidemiologist Daniele Fallin, PhD, of Johns Hopkins Bloomberg School of Public Health

My work focuses on autism and understanding how genes and environments interplay to cause this developmental disorder. Much of this work is funded by federal grants, but there can be gaps in what these grants can support, especially in new fields of research. Support from Autism Speaks has been amazing in helping fill these gaps.

In particular, Autism Speaks provided important support for two of my current projects. The funding is allowing us to study families with autism and, so, gain insights into  interactions between autism risk genes and environment exposures.

The Early Autism Risk Longitudinal Investigation (EARLI) is a national study of families that have at least one child on the autism spectrum and anticipate having more children. By following these high-risk families we seek to identify causes and risk factors—be they genetic, environmental or a combination of both. Information is regularly collected from mothers enrolled in the study, and their newborns receive free developmental assessments until 3 years of age.

The second study is a genome-wide investigation of DNA methylation, or epigenetics. It will allow us to investigate how various environmental exposures can affect gene expression in ways that increase—or potentially decrease—the risk of autism. This study will place special focus on environmental exposures during crucial periods of prenatal brain development.

Autism Speaks realizes the importance of these new areas of research and has put forth great effort to ensure we can explore and, hopefully, uncover risk factors for autism that, over the long term, may lead to prevention and improved treatments.

We continue to recruit study participants. Specifically we are enrolling mothers who have one or more children with autism and who may become pregnant or who are currently less than 28 weeks pregnant. They must live near an EARLI research site (California, Maryland or Pennsylvania). For more details, please visit www.EARLIstudy.org or our Facebook page.

On behalf of the EARLI research team, I want to extend a special thanks to Autism Speaks supporters for helping make this pioneering research possible.

Explore more of the studies our supporters are funding with our Grant Search Engine. And read more autism research news and perspective on the science page.

Transcript of Today’s Office Hours Webchat

January 5, 2012 3 comments
Office Hours Webchat with Geri Dawson and Joe Horrigan Jan 5. Thanks to the more than 200 readers who joined us. As time allowed answering just a portion of more than 100 questions, we hope you’ll join us again next month—Feb. 2 (first Thursdays) at 3 pm Eastern.

 

Thursday January 5, 2012

2:56
Hi Everyone! We are just getting ready to begin!

 2:56

3:00
Hello everyone, this is Dr. Dawson. Welcome to the webchat. We’re glad you are here. Dr. Joe Horrigan and I are here and ready for your questions.

3:00

3:00
Hello everyone – yes, this is Dr. Joe Horrigan and I am here, too.

3:00

3:00
Advance question from LINDSAY: My 3 year old son has not been diagnosed as on the autistic spectrum at this time, however I have that gut mom feeling that he is on the spectrum. He went through the First Steps program from 18 months to his third birthday. He was evaluated by our school system and is now attending half day preschool five days a week. During that time he sees attends speech for two fifteen minute sessions. He especially needs help with his language both receptive and expressive. My question is what is my next step in finding a private place that deals specifically with autistic kids so that he can get a more intense therapy for his language delay? Also, is this kind of therapy covered by most insurance plans or are there other avenues to get it covered?

3:00

3:02
Hi Lindsay, This is Dr. Dawson. If you feel that your son might be on the spectrum, I encourage you to see a specialist – either a physician or psychologist – who specializes in autism and can provide a proper evaluation. If he does have autism, this will open the doors to intervention programs and services. Autism Speaks resource guide (http://www.autismspeaks.org/community/resources/index.php) can help you locate services. Speech-language therapy is usually covered by most insurance plans. Specialized autism treatment, such as applied behavior analysis, is sometimes covered depending on where you work and the state you live in. Follow your instincts and I wish you the best!

3:02

3:04
[Comment From Guest Guest : ]Me and my husband do not see eye to eye with our son is there anyway to find a common ground?

 3:04 Guest

3:05
Hello, It is common for parents to disagree about what is best for their child. Find a time when the two of you can spend some quiet alone time together and allow time for each person to express their feelings and concerns. Really listen, reflecting back what you have heard. Then, see if there is a way of coming up with a solution that you both feel comfortable with. If you continue to have difficulty seeing eye to eye, meet with a professional and discuss the issues you disagree about with this person, who can help you be more objective and promote a healthy dialogue.

 3:05

3:07
[Comment From Rachel Rachel : ]My son was diagnosed with PDD and Klinefelter’s in June. He had a feeding tube placed in March 2011 and is still not eating. He will be 3 in March. Any suggestions?

3:07 Rachel

3:09
Hi Kim, This is Dr. Dawson. It is not uncommon for young children with autism to recognize letters even before they start saying words. She can see the letters and use her visual skills, which may be stronger than her auditory skills. Playing games by pointing to and naming letters can be a way of stimulating her language development, so I encourage you to continue to interact with her by playing letter games.

 3:09

3:09
[Comment From Kim SmithKim Smith: ]I have a 2yr old daughter. Actually 27months old now. She doesn’t say any words at all, but she does recognize a few letters, A B C D E P T, not consistently but at times. I constantly work with her on letters. Because she has ADS/sensory issues, is she just repeating these because she’s recognizing them or could this truly be a preface to her ability to speak. what do you think??

3:09 Kim Smith

3:10
Rachel: This is Dr. Horrigan. It would be good to know if your son has had a formal GI workup completed, to look at potential biological or physical causes for his not eating, and to know what they found, especially if they did a biopsy. Also, a skilled dietician and/or speech therapist could be quite helpful, in terms of determining if there are any windows of opportunity in terms of your son’s preference for particular tastes or textures. There have been occasions, usually with older children, when we have to, out of medical necessity, use medicines in an off-label manner to augment appetite – examples would be cyproheptadine or risperidone or mirtazepine. Again, this is “off-label”, but sometimes we have to do it out of medical necessity.

3:10

3:12
[Comment From MicheleMichele: ]My Granddaughter is six years old, she can read at sixth grade reading level, she writes, she speaks a little bit of several languages self taught googler. yet, I rarely get a direct answer from her. Sometimes I do, sometimes I don’t. Suggestions on communication would be so helpful. One more thing, she has the most violent temper, what are the best means of disipline for kids with Autism.

3:12 Michele

3:14
Hi Michele, This is Dr. Dawson. Even after children with autism develop many skills, such as reading and even speaking in different languages, they can continue to have difficulty in the social use of language, especially with conversation skills or responding to questions that she might not be interested in. Before engaging her in a conversation, be sure to take a moment to get her attention and then state the question in a simple direct manner, even providing visual cues such as gestures. If she doesn’t respond, you can prompt her to respond by giving her choices of responses (“Do you want X or Y?”) or even providing the beginning part of her answer. She is fortunate to have such a caring grandmother.

3:14

3:16
[Comment From GuestGuest: ]My daughter Madi is 10 almost 11 she has autism and is just starting puberty. I have never seen her so anxious like she has been these last few months. I have a dr.’s appointment to talk about medication for anxiety but, we are currently not on any, What types of med’s do they put such young children on?

3:16 Guest

3:18
Dear Madi’s mom: hormones such as estrogen and progesterone can definitely influence mood, as can the hormones from the brain that stimulate their production. Changes in these levels can trigger anxiety, including episodes that feel like ‘panic attacks’, sometimes associated with an emerging menstrual cycle, and this is not uncommon when there is a family history of bona fide anxiety disorders. In terms of medications, I suspect that you may end up talking with Madi’s physician about options such as an SSRI (e.g. fluoxetine, sertraline), starting with very low doses, or perhaps even a low dose of a benzodiazepine such as clonazepam, if there is a clear medical need because the anxiety is becoming disabling. I suspect that the degree of anxiety may settle down somewhat once Madi passes through menarche and commences regular periods, but that come take some time…

 3:18

3:20
[Comment From DesiDesi: ]I am a concerned sister my brother has been displaying very defiant attitude about going to school and doing his routinely schedule. He also has this tendency to lash out and talk to his hands naming them Oobi and Uma… He does very forcefully and it happens about 53 times an hour. His school brought this attention to us this summer 2011. His teachers have noticed he is doing this more and more which deters and delays the time to complete a task. Would you happen to know what this is?

3:20 Desi

3:21
Hi Desi, This is Dr. Dawson. The behaviors you are describing are common in children with autism. Your brother is having trouble knowing how to express his feelings in an appropriate manner. When he gets frustrated, he likely doesn’t know how to express his frustration using words, and therefore he lashes out. Repetitive behaviors are also common. Both the lashing out and repetitive behaviors can helped through behavioral interventions and sometimes with medicine. To find resources, take a look at Autism Speaks resources library.

3:21

3:21
http://www.autismspeaks.org/family-services/resource-guide

3:21

3:22
[Comment From LaurenLauren: ]How often do you recommend having a child see a developmental pediatrician? My daughter saw one just over a year ago and is in an intensive school program, but I haven’t taken her back to the dev. ped. Should I take her every year or ever six months, etc??

3:22 Lauren

3:22
Lauren: This is Dr. Horrigan. Every six months is fine, in my opinion, if everything is going reasonably well, and there are no specific medical or psychiatric concerns that merit the use of medication. I would look at a more frequent pattern of visits to a developmental pediatrician if your daughter is not making the gains that you expect, or if you are wondering if medicine might be a useful part of her treatment plan.

3:22

3:23
[Comment From GuestGuest: ]Hello, Doctors. I am a college student majoring in biology. Last summer, I managed a summer camp for adults with intellectual disabilities, and was inspired to specialize in autism when I (hopefully) attend medical school. I was wondering what inspired each of you to enter into this field of research?

3:23 Guest

3:23
Hello – This is Dr. Dawson. Like you, I was inspired to devote my career to autism at an early age. I babysat for twins with autism in high school. At that time, there was so little known about how to care for and help people with autism. We have made a lot of progress but we have a long ways to go and we need people like you to join the effort.

3:23

3:26
[Comment From GuestGuest: ]My 3 year old was just diagnosed on the spectrum 3 weeks ago. His IEP has been developed and his first day of special ed pre k was today! One of the things we will be working with is communication thru pictures. I’ve looked up info regarding PECS and similar. It is not in our budget to purchase PECS currently. Do you know of any other resources/options? Thanks.

3:26 Guest

3:26
Hello, This is Dr. Dawson. PECS and other visual communication systems can be very helpful in promoting language development in young children with ASD. Your school should provide you with an identical set of pictures that they are using so they can be used at home. Many times, these are handmade and can even involve photos taken by parents and teachers. You don’t have to necessarily use pictures made by a company. Here is a link about the use of visual supports:

3:26

3:27
http://www.autismspeaks.org/science/resources-programs/autism-treatment-network/tools-you-can-use/visual-supports

3:27

3:28
[Comment From GuestGuest: ]How do you decipher how to treat co-morbidity with ASD and associated disorders such as GAD and ADD? My child has a combination of these and it is difficult to tease out cause and effect or primary vs. secondary – especially in social situations where the ASD is present and so is the ADD impulsivity. THANK YOU!!

3:28 Guest

3:30
Dear Guest: This is Dr. Horrigan. You are absoloutely right – it is tough to disentangle common co-morbid conditions, such as co-morbid anxiety, especially if the youngster’s degree of developmental disability is more substantial. This is one of the reasons why I like to spend a lot of time taking a good family history, especially to look at who in the family (mom, dad, brothers, sisters) might have common psychiatric conditions that are known to be heritable and can be readily treated – you mentioned two of them – anxiety disorders and ADHD are two good examples. Then we decide if we want to use medicine as part of the treatment package for the youngster with ASD – if we do, we typically start with much lower doses than the prescribing information typically indicates, and we pick a medicine that is keyed to the specific difficulties that the youngster is facing. An example would be something like clonidine for a youngster with ASD that is very hyperactive/impulsive.

3:30

3:32
[Comment From lisalisa: ]I am an SLP and would like your insight on a client. He is 6 and nonverbal…uses some signs and pictures for communication very effectively. he has a history of aggressive behaviors that we think were related to gastro issues and underlying strep. those are taken care of now and aggression is only when he doesn’t get his way…very developmental behavior. Now, however, sometimes he gets this very confused look on his face and then starts to cry…a very pitiful cry. A hug makes it better for a while. he is also having a terrible time in public…restaurants, church….has huge meltdowns, bites, scratches…..

3:32 lisa

3:32
Hi Lisa, This is Dr. Dawson. Autism is often associated with medical issues, such as gastrointestinal problems, so it is great that you were aware that this boy was suffering and got the treatment he needed. You should keep a careful record of the times when he starts to cry to see if you can determine what is eliciting this. Perhaps it is something you can change. The important thing is to continue to help him learn to communicate his needs and feelings, so that he doesn’t have to resort to meltdowns and aggressive behavior. If you can anticipate when he is starting to get upset, you can prompt him to ask for a break or help by using a picture, word, or gesture, instead of having a meltdown.

3:32

3:33
[Comment From annann: ]My son is taking intuniv 2 mg it seems to be helping but I am being told by other parents that he should be in a combination of stimulant plus intuniv

3:33 ann

3:35
Ann: This is Dr. Horrigan. It is not a problem for your son to take Intuniv (guanfacine) by itself. If it is helpful for your son, and it is well-tolerated, by itself, that is fine. It can work well on its own for impulsivity/over-activity and to some degree for inattention/distractibility. The fact that it has been studied alongside stimulants is helpful additional information, but it does not confine how it is used by thoughtful clinicians.

3:35

3:36
[Comment From MichelleMichelle: ]How do we handle discipline in our 4 year old.. limited verbal child? My husband, our child’s school and myself are all addressing it differently and it seems none of it is working!

3:36 Michelle

3:38
Hi Michelle, This is Dr. Dawson. Is your child participating in an intervention that uses applied behavior analysis (ABA)? If not, to find out more about ABA, you can check out this link on Autism Speaks’ website. See link below. The methods of ABA should be used to help discipline your child with autism. The method involves providing a routine and structured environment, breaking down the things you want your child to do into small easily understood steps, teaching each of these steps often with much repetition, and then reinforcing each behavior using those things that your child specifically finds reinforcing.

3:38

3:38
http://www.autismspeaks.org/what-autism/treatment/applied-behavior-analysis-aba

3:38

3:42
[Comment From AishaAisha: ]My son was diagnosed with ASD at 3yrs old the fall of 2010 and now this past fall 2011 he was diagnosed with ADHD. I want to know if this is common?

3:42 Aisha

3:42
Dear Aisha: This is not uncommon. ASD usually trumps the clinical picture, especially if the if the degree of disability is more severe, and the younger the child is. Also, DSM-IV discourages an ADHD diagnosis if autism is diagnosed as the primary condition. However, for many individuals with ASD, as the severity of their core ASD symptoms subside with maturity, it is not uncommon for the residual inattention/distractibility/hyperactivity/impulsivity to be the key disabling features that remain, and this become more evident as the school curriculum becomes more cognitively (and behaviorally) demanding.

3:42

3:43
[Comment From LaceyLacey: ]Hi! I have been looking forward to this all week!! We started trying to get my almost Three year old daughter tested in September and I am very frustrated. We got a ref. from her Pedi. to early intervention. They called us after a few weeks and said that it would be better for us to go through the school board. We gave them all of our information and than weeks went by with no contact from the school board. I called them back and they said that they did not have our paper work. We did the inital testing on Dec 13th. The lady told us that she strongly suspects ASD and that she needs more testing done. They said to expect an appointment letter sometime in Feb. I did not want to wait that long with no information so I started trying to find a private dr. What a night mare. Call the insurance company and got a phone number. Called the dr and they said that we should wait until after the holidays so that she would be closer to 3 for testing. I called back Jan 2nd and was told that the dr was no longer accepting new pts. After explaining the situation they said that they would call me back after talking to the dr. The did not call me back despite me leaving 2 more messages over the next Two days. I got in touch with them again and they told me that she could start seeing a social worker that will be out until March. Should I wait that long? If so what do I do in the mean time? I feel like I dont know what to do with her. Like when she has a melt down I just kind of hold her.

3:43 Lacey

3:44
Hi Lacey, This is Dr. Dawson. What you are going through sounds so frustrating. I know you are eager to get started helping your child right away. I recommend that you check out Autism Speaks resource library which will show you the providers in your area. Keep calling until you find someone who will see you as soon as possible. Your local Birth-to-three center should see you right away. You can get started in speech-language therapy even before you have a formal diagnosis for your child. Also, there are many good books that explain things you can do at home to help your child. I recommend Overcoming Autism by Lynn Koegal. Check out Autism Speaks 100 day kit for more information about how to get started and find resources.

3:44

3:44
Resource Library from Family Services:
http://www.autismspeaks.org/family-services/resource-library100 day kit:
http://www.autismspeaks.org/family-services/tool-kits/100-day-kit

3:44

3:47
[Comment From CourtneyCourtney: ]My Son has been Biting the Inside of his Lip happens when he is upset, board, Or super excited! Now It is A big sore!! Witch is now Reacting with his eating!! What can I do to Stop or speed up the Healing?

3:47 Courtney

3:48
Courtney: This is Dr. Horrigan. You can also speak with a dentist, but it sounds like your son may have one or more apthous ulcers in his mouth from the accidental biting. Sometimes l-lysine can be helpful, but you have to really crush up the pills to make them easy to swallow if the ulcer(s) really hurt. Occasionally oral herpes can masquerade as, or look like, SIB mouth sores, in which case there are other medicines for that. But I think a dentist should take a look, to figure out what might be going on….and to make a proper diagnosis.

3:48

3:50
[Comment From RobinRobin: ]My son is 11. DX with Asperger Syndrome. He hates school and seems to be very angry all the time. He is extremely bright but of course is lacking in social skills. Are there major behaviour changes related to puberty? is this anger normal? He is not angry all the time but he gets very frustrated easily and he screams at people!

3:50 Robin

3:50
Hi Robin, This is Dr. Dawson. The problems you are describing are not uncommon but it would be good to see if there is a way to help your son be happier, especially to enjoy school since he is so bright. Puberty brings many changes – both hormonal and social – can result in higher levels of emotional outbursts and anger. The first thing is to try to understand what it is about school that he hates. Is it the classroom structure, the academic material (is it interesting, boring, too challenging), his lack of friendships, or possibly bullying or teasing? Meet with his teachers to discuss your concern and see if you can make changes at school that will help him enjoy it more. Social skills training, which includes teaching a child had to manage their emotions and outbursts, can be very helpful. Check out Autism Speaks resource library to see if you can find a psychologist or behavioral specialist or social skills group in your area. You can find the link here:

3:50

3:51
http://www.autismspeaks.org/sites/default/files/documents/atn/transition_from_pediatric_to_adult_services.pdf

3:51

3:52
Hi JM, This is Dr. Dawson. Your brother is fortunate to have such a caring brother! Check out Autism Speaks transition kit (above) – it describes in detail how to help an adolescent with ASD transition successfully from high school to college.

3:52

3:53
[Comment From JMJM: ]My brother has Asperger’s and is getting ready to go to college this semester. How can my parents prepare him?

3:53 JM

3:55
[Comment From ShannonShannon: ]Hi, my son is 7 years old and has aspergers. He is also diagnosed with ADHD, sensory, and anxiety disorder. He has had so many changes in his life, we recently had to move in with my parents because my husband lost his job as a manager. My son is on focaline (15 mg AM), intuniv, and ritalin (5 mg at 4pm). He is having major issues at school and anxiety. He worries about the smallest thing and freezes answering the simplest questions (like 2 plus 2). He does see a therapist without any luck and the school feels like there is emotional barriers. But he is failing second grade regardless of us or the school helping. He use to be a straight A student and now he pulls C’s, D’s and F’s. Is there anyway (without medications) to lesson his anxiety or help him through this? We do play therapy but he seems to be getting worse to the point of effecting his gastrointestinal. He seems to pick fights and lie quite a bit at home. At school he runs to the nurse for every little thing or is late to class regardless of us dropping him off early. I believe it’s avoidance? Anything to subside his anxiety?

3:55 Shannon

3:56
[Comment From DonnaDonna: ]I am a bus aide for special needs children and I was wondering what is the best way to introduce change to autistic children

3:56 Donna

3:56
Hi Donna, This is Dr. Dawson. As you probably are aware, children with autism often resist change and can become upset by any change in routine. If you can anticipate a change ahead of time, it is most helpful. You can explain that things will be different (for example, the bus will be coming at a different time or take a different route) and illustrate this using pictures, if possible. Check out Autism Speaks visual support tool kit at this link:

3:56

3:57
VISUAL SUPPORTS: http://www.autismspeaks.org/science/resources-programs/autism-treatment-network/tools-you-can-use/visual-supports

3:57

3:58
Shannon: This is Dr. Horrigan. I think that the difficult changes that have occurred in your family’s life, mostly of which are not directly amenable to simple interventions, are influencing your son’s behavior. I am sure you are doing an excellent job at giving him the most emotional support that you can, given all that is happening. It would be good to know if there have been any recent changes in his school setting, as well, that could be contributing to how he is feeling and acting. In the meantime, to focus on the last part of your last question, when stress reaches ‘catastrophic’ levels, we sometimes use a small amount of risperidone or aripirazole, as examples, to dampen down catastrophic reactive outbursts. SSRIs are also an option – see my previous comments about this class of medicines in one of my earlier responses. I am also left wondering why your son is simultaneously taking Focalin and Ritalin; I would want to make sure that there is a good reason for that…sometimes, they make anxiety worse…

3:58

3:59
[Comment From Suzanne B.Suzanne B.: ]My 8yo son has had chronic constipation since birth. Dx with ASD at age 3.5, with ADHD at 6. We’ve been using Miralax for years, but he sometimes gets backed up and requires an enema. We are trying regular toilet training (after breakfast and dinner) to encourage his system to regulate. My question is about diet. He is a “good eater” (when the amphetamines aren’t suppressing his appetite), and loves all kinds of food. So, I’ve been reluctant to try the GFCF route with him (add inflexibility to an otherwise relatively flexible Aspie). I wonder what you folks think — have you seen benefits to removing casein and gluten in this situation?

3:59 Suzanne B.

3:59
Hi Susan, This is Dr. Dawson. Psychologists and neuropsychologist both have training in behavioral health, but a neuropsychologist has special expertise in testing specific functions of the brain, such as attention, memory, and so on. The neuropsychologist can be especially helpful if you are concerned that your child has a learning disability.

3:59

4:02
[Comment From LisaLisa: ]My almost 4 year son was recently diagnosed with ASD. We also have a daughter in first grade (6 years old) not ASD. What is a good age for us to explain her brother to her? Is too young to understand what autism is?

4:02 Lisa

4:03
Hi Lisa, This is Dr. Dawson. This would be a good time to explain your younger child’s autism to your daughter. She is old enough to understand and it will help her explain her brother’s unusual behaviors to her friends. Check out these links on Autism Speaks’ website that provide resources for siblings.

4:03

4:03
[Comment From GuestGuest: ]What are your thoughts about the value of weighted blankets and weighted lap pillows? My 11 year old son was diagnosed with Aspergers in the 1st grade. His biggest challenge is the ADHD symptoms for which his physician put him on Ritalin. I, however, prefer non-drug methods when possible. He also suffers from sleep issues and is rarely rested… I made him a lap pillow from rice and an old pillow case and he says it “works” but sometimes he just tries to tell me something works because he thinks that’s what I want to hear… I don’t have time (or skill) to make a (safe) weighted blanket, but didn’t want to spend $ on one if it may not be helpful… any other suggestions?

4:03 Guest

4:04
Dear Guest: This is Dr. Horrigan. My experience with weighted blankets has been hit-or-miss. Sometimes they are helpful when there is a clear-cut degree of tactile defensives or if just-the-opposite (flat-out seeking of pressure/contact/hugs/body contact) is present, but you don’t know if it will help until you try it. I would try going up progressively on the weight (e.g. adding progressively more amounts of rice), and asking your son in a clear manner how it feels, if he likes it. If his answers are fuzzy or unconvincing, I wouldn’t persist. They are not for everyone, and I know the branded products can be expensive.

4:04

4:05
From S. Wong
Hello, I have a question regarding my 6 year old son with Autism, who has many food allergies. In a routine urine dipstick and culture test at his Pediatrician’s office in May 2011, we found out through 2 separate urine tests that he repeatedly has a small amount of blood in his urine, but no infection or fever. Again in a follow up in December 2011, he showed a trace amount of blood, in addition to a small amount of protein, with no other symptoms. I suspect that this is a chronic problem with my son, who eats a lot, but has not much weight gain(less than one pound) in the last 6 months. The pediatrician suggested a follow up urine test in a month, but she does not show concern about the small amount of blood and protein.
I would like to know if the blood and protein in urine is considered normal, and if not, what other tests should be pursued to determine the cause? The only supplement that my son is getting is Culturelle and methyl B-12 shots/ once every 3 days. Thank you!

4:05

4:06
SW: This is Dr. Horrigan. There are instances in which people can have a very small amount of blood in the urine and it is not associated with a disease or disorder, and the same would be true for a small amount of protein. What is seen when the urine is looked at under a microscope is important, as is the result of blood tests such as creatinine and BUN. This helps determine whether more substantial testing (e.g. renal ultrasound, or other type of imaging, or maybe even a biopsy) is needed. Also, I would want to know if your son is anemic (low red blood cell count), and whether that influenced your decision to implement methyl B-12. In terms of growth, it would be good to know if your son is staying on his height growth curve, and the degree to which he has shifted away from his normal weight curve – this CDC web site gives an example of the curves that I am talking about (http://www.cdc.gov/growthcharts/data/set1clinical/cj41l021.pdf ).

4:06

4:07
Advance question from Shane: I currently work for an agency that offers an intervention program for infants and toddlers with autism. The program is family-focused in that the vast majority of intervention is aimed at teaching the parents how to intervene, rather than the more traditional aide-based model. In our view, the family is the centre of a child’s life. Teaching parents how to support their child independent of external supports is the greatest strength of our intervention program. However, this model is not without barriers. The most notable barrier to providing this intensive parent intervention is that many of the parents are only weeks from their child’s diagnosis and have yet to adjust to how their life will be different having a child with autism. Understandably, many of the families are simply not ready to participate in the intensive training; they are often not in the right ‘head space’ to participate in the intervention process and would rather Aides provide the support. What advice would you offer to families who find themselves in this moment in their lives? Further, what strategies would you offer to the staff of the organization in finding the balance between helping to support the family while maintaining the intensive philosophy of the parent-focused intervention?

4:07

4:08
Hi Shane. This is Dr. Dawson. It is important to meet parents where they are as you begin your work together. First, if a parent is showing signs of depression or anxiety or is having significant marital distress, referral to a specialist –either a physician or psychologist working in these areas – is recommended. Second, talk with the parent about the things that matter most to his or her. What does the parent find most challenging right now? Is it the inability to communicate? Is it a problem with eating? Is their child having frequent tantrums or aggressive behavior? Start by having the parent identify an area of concern and then help him or her learn strategies for dealing with that concern. If needed, start slow and establish very small goals so that the parent can quickly experience success. It could be as simple as finding appropriate toys or establishing a bedtime routine. Once a parent sees progress – however small – this usually helps alleviate stress and increases optimism and motivation.

4:08

4:09
[Comment From MichelleMichelle: ]Hi! I have a 9 year old son with autism. Lately his flapping has gotten really bad. He flaps near his hear so bad that his ears get red and he scratches his neck. I don’t see any other symptoms that are out of the ordinary, could this just be a phase or should I be concerned? Any suggestions?

4:09 Michelle

4:11
Dear Michelle: This is Dr. Horrigan. Yes, it could just be a phase, as you suggested, but I am wondering if your son is choosing this specific reptetive behavior for a reason. What is coming to mind is whether he has an ear problem; I am thinking about everything from lots of itchy ear wax to a foreign object (e.g. bead in the ear canal) to an ear infection. Has your son’s pediatrician been able to use an otoscope to look in his ears? Otherwise, it will be important to determine the context in which the flapping is occurring, to see if there is a behavioral manuever that can be implemented to redirect it before it gets too severe…

Thursday January 5, 2012 4:11

4:12
Hello. My name is Annette. I am a mother of eleven children. Seven boys… four girls, three of my boys are Autistic, ages 12, 11 & 9. My oldest daughter passed away in a car accident on Dec. 04-11. I explained to my children all at the same time about the death of their sister. I wonder if my three boys really understand what happened and what it means that their sister is now in heaven??? Please help me understand if there is a way to explain it to them that I might try. It’s kind of like the Groundhogs Day movie…. repeating itself over and over with my boys. Thank you

4:12

4:13
Hi Annette. This is Dr. Dawson. I am really sorry to hear about your daughter’s death. You have your hands full with so much responsibility. This must be a very difficult time for you. If your three boys are asking you about it again and again, then you do want to help explain what happened. I suggest you create a “social story” – in other words – a set of pictures that illustrate that their sister was in an accident and her body stopped working and she is now in heaven. Remember that kids with autism are very literal. They may have a hard time understanding that she won’t come back. Even though they are 12, 11, and 9, their ability to understand what happened will be more like a preschool age child. Here is a website that explains how to talk with a preschooler about death: http://www.babycenter.com/0_how-to-talk-to-your-preschooler-about-death_65688.bc?page=2#articlesection2 . Even though it is tiring to respond to their questions again and again, calmly reiterate what happened. Be sure to find the support you need. There are local support groups, as I am sure you know, for parents who have lost a child. Talking with other parents and professionals will help guide you and provide support.

2 4:13

4:14
Advance question from Sheetal: Do autistic babies/toddlers often start to babble much later than typical babies/toddlers and does their babbling differ in any way. Why do teachers and speech therapists often say that it’s a “positive sign” when an autistic baby/toddler produces consonant sounds in babbling even when they have not begun to speak any words yet?

4:14

4:15
Hi Sheetal. This is Dr. Dawson. Studies have shown that infants and toddlers with autism are delayed in babbling and, when they do babble, often they don’t make the same sounds as a typical baby. They make fewer consonant-vowel sounds, such as da-da and ba-ba. Babbling sounds are the building blocks for language, so it is a very positive sign when a toddler with autism begins making these sounds. Therapy can then build on these sounds to “shape” them to become simple words. For example, ba can eventually become ball. When a toddler with autism makes sounds, it is important to reinforce them by imitating them and playing sounds games

4:15

4:16
Comment From Andrea:
Hi Doctors! I have a 22 month old daughter who has been getting aba therapy since she was 18mos.Research has shown that 40 hours a week of therapy gives the best results. So why is it that all of my daughter’s providers don’t agree? She is currently getting 6 hrs a week of aba which will be increased to 10 and we will be adding 1.5 of speech too.

4:16

4:17
Hi Andrea, This is Dr. Dawson. Although early studies on ABA were based on 40 hours of therapy per week, more recent studies have used fewer hours with positive outcomes. For example, in a study that my colleagues published in 2012, toddlers received 20 hours of therapy from a trained provider and parents provided additional help at home by using the therapeutic techniques during their daily routines. The National Research Council, a body comprised on independent experts that inform policy, recommended that young children with autism receive 25 hours of structured intervention each week. This can be comprised of different therapies (ABA, speech-language, and so on). For more information, download Autism Speaks 100-day-kit (http://www.autismspeaks.org/family-services/tool-kits/100-day-kit).

4:17

4:18
Advance question from LS: Not to identify myself and anger my family involved… may I just ask: Could it be possible that a parents life, pre-parenthood, be responsible for creating risk factors of autism in future children? Such as, doing a large amount of drugs in adolescents and early adulthood? Or just certain kinds of illegal drugs being more likely than others to effect their reproductive organs, in either or both future parents?

4:18

4:19
LS: This is Dr. Horrigan. “Epigenetics” is an emerging field that examines the factors that influence whether or not a gene or genes are biologically active. This is different from the study of “genetics” which tends to focus on whether a particular gene or a version of a gene is present or absent. We now know that a wide range of factors such as substance abuse (e.g. cocaine) to stress (which can raise internal levels of hormones that can impact gene expression) are important epigenetic influences, in general, and they can play a material role in the expression of subsequent psychiatric disorders as well as medical illnesses. However, the study of relevant epigenetic factors in autism is at an early stage, and it is too soon to make definitive statements about the role of particular influences such as substance abuse in parents. I anticipate that several relevant epigenetic factors that can clearly influence autism expression will become evident within the next decade, as this is a focus of a lot of ongoing research.

4:19

4:19
[Comment From clairclair: ]i have a 17 year old daughter who is severly autistic and over the last year has displayed rapid cycling behaviour how difficult is it to seperate mental health problems from the autism?

4:19 clair

4:21
Dear Clair: This is Dr. Horrigan. I have to leave in a moment, but I think the best approach is to systematically gather data to look at your daughter’s pattern of cyclist. Then you would look for whether there are environmental/programmatic/contextual things that are occurring that sync up with the times when things are going bad. If not, you then think about psychiatric (or neurological) co-morbidities. For example, bipolar disorder certainly has a cyclical pattern, when it is actually present, and we look carefully at the specific behavioral changes that occur to see if they fall into the manic/hypomanic spectrum before rendering that diagnosis. To make that diagnosis, a family history of mood disorders is also critically important, as is the presence or absence of common accompanying medical difficulties such as migraine headache, atopic disorders (e.g. eczema) and asthma…as examples…. also it would be good to assure that features of a seizure disorder are not present (e.g. complex partial seizures)…this would require a formal neurological evaluation…as a final note, we oftentimes use anti-seizure medicines to treat bipolar disorder

4:21

4:23
Advance question from María in Argentina:
Thank you for this opportunity. I live outside USA but I do think that the situation is similar to USA in these topics
1-Why the psychiatric paradigm is considered the most helpful when there are many unmet needs in families with children diagnosed with ASD of Concomitant medical problems (CMPDs) from immune dysfunction to abnormal answer to strep/herpes infections through GI problems?
2- Why the Early intervention programs do not include biological exploring of CMPs as a routine- not the usual ones, but considering the state of the art in the abnormalities of different subgroups of children with ASD? The combination biology-education has been the most helpful to us in practice- not the psychiatric-genetic.
3-Why are there not efforts to include protocols in practice that take into account the CMPs in children diagnosed with ASD?
4-Why the inflammation and oxidative stress are not routinely explored and treated if present in different subgroups of ASD children?
5-What efforts are being done to these problems to be addressed in practice ?

4:23

4:24
Hi Maria, This is Dr. Dawson. What we now know is that autism is not solely a dysfunction of the brain. It affects the whole body. Autism is associated with a wide range of medical conditions, including as you point out, gastrointestinal problems, oxidative stress and metabolic problems, such as mitochondrial dysfunction, among others. In addition, it is important to screen for exposure to toxins, such as lead and others. Autism Speaks Autism Treatment Network (http://www.autismspeaks.org/science/resources-programs/autism-treatment-network) is devoted to understanding and treating these medical conditions. In addition, we are funding studies on immune dysfunction and infections, mitochondrial dysfunction, oxidative stress, exposure to toxins, and so on. We are investigating biomarkers that could identify children who have specific medical conditions. If these medical conditions are not addressed, we know that children cannot fully benefit from educational and behavioral interventions. Medical conditions can also contribute to problems with aggressions, self-injury, and attention difficulties. Treating the “whole child” is essential to any intervention program and requires a multidisciplinary team.

4:24

4:25
Advance question from STACY: Can an aspergers diagnosis be made if there are minimal to no repetitive behaviors present and the child has some language impairments?….language was slightly delayed but really just more scripted with echolalia till therapy interventions. Language is much more meaningful now. I would like to discuss this with my son’s developmental ped but just wanted some more info first.

4:25

4:26
Hi Stacy, This is Dr. Dawson. Children with Asperger syndrome do not show significant cognitive and language impairments, although slight delays in language are possible. To qualify for a diagnosis of Asperger syndrome, there needs to be evidence of a restricted range of interests/activities or repetitive behaviors, although this can be manifest in many different ways. I recommend that you talk with your doctor about getting a referral to a clinician who specializes in the diagnosis of Autism Spectrum Disorders. To find one in your area, visit Autism Speaks Resources page (http://www.autismspeaks.org/family-services/resource-guide).

4:26

4:27
Thank you all SO much for joining us. Please join us next month, Feb. 2, and every first Thursday at 3 pm Eastern. Be well!

4:27

Base Pairs to Bedside: A Visit to Beijing Genomics Institute

November 10, 2011 Leave a comment

From left: Drs. Yonghui Jiang, Andy Shih, Huanming Yang, Geri Dawson, and Clara Lajonchere

Posted by Autism Speaks Vice President of Scientific Affairs Andy Shih, Ph.D.

Beijing Genomics Institute (BGI), the world’s largest genome sequencing organization got its start a little more than a decade ago at a moment when idealism, patriotic fervor and more than a little chutzpah converged to create what one of its founders, Huanming Yang, Ph.D., recently acknowledged was “a Mission Impossible.”

Yang, then with the Chinese Academy of Sciences, promised to complete 1 percent of the Human Genome Project–at the time the biological equivalent of the moon shot of the 1960s. There was just one problem: He didn’t have a gene-sequencing machine!

What followed was one of the most thrilling rags-to-riches stories in modern science. Yang and his colleagues overcame immense technical, financial and political obstacles to deliver the DNA sequence of their portion of human chromosome 3. In doing so, they changed Chinese science forever and built a scientific-industrial juggernaut that now represents 20 percent of the world’s capacity for genome sequencing.

That same can-do spirit was clearly on display when I and Autism Speaks-funded Duke University researcher Yong-hui Jiang, M.D., Ph.D., visited BGI in Shenzhen after the Autism Research Collaboration Development Meeting, co-hosted by Children’s Hospital of Fudan University in Shanghai and Autism Speaks. Not coincidentally, Yang gave the keynote address to the meeting, which ended last weekend.

Today most of BGI is housed in a former shoe factory on a small campus that includes several high-rise dormitories for nearly 4,000 employees. In recent years, the institute has produced such high-impact scientific accomplishments as complete genome sequences of rice and potato plants and the human gut microbiome (our digestive microbes). Through genetic sequencing, it also identified the culprit behind this summer’s deadly E. coli outbreak in Germany. In the face of this public health crisis, BGI marshaled the staff and technology to sequence the entire genome of the toxic bacterial strain in less than three days.

From left: Yirui Li (BGI), Yonghui Jiang (Duke), Jian Wang (BGI), Andy Shih, Jun Wang (BGI), and Hongle Chen (Jet Li’s One Foundation) in front of a picture of Mount Everest taken by Dr. Wang

In visiting BGI, I was impressed by more than the arrays of cutting-edge automated sequencers, which run 24/7. I was struck by BGI’s eclectic leadership.

BGI cofounder, Jian Wang, Ph.D., recently scaled Mount Everest, after three attempts over a two-month period. For inspiration he credits BGI’s landmark collaboration with U.S. and European scientists in documenting the rapid evolution of the Tibetan human genome to accommodate life at high altitudes.

BGI executive director Jun Wang, Ph.D., joined the institute when he was 23 and went on to amass 36 publications in Science and Nature over 12 years. For your average researcher, having 1 or 2 publications in Science or Nature is sufficient to secure a tenured position at a top U.S. or European university.

At age 25 years, Yirui Li is leading the bioinformatics efforts of BGI’s recently announced collaboration with Autism Speaks to sequence 10,000 autism genomes. With 16 Science and Nature publications to his name, Li dropped out of China’s elite Tsing Hua University at age 19.

Despite their intellectual firepower, drive and personal and professional accomplishments, they were a down-to-earth group. They thought nothing of coming in on a Sunday to meet with us. Sporting what appeared to be their regular uniform of T-shirts, jeans and flip-flops or running shoes, they looked more like grad students than high-profile executives of a leading international research institute.

Yang and his colleagues also have a refreshingly progressive view on science and its end game. Impatient with traditional distinctions among scientific disciplines–such as genetics versus environmental sciences–they advocate a “trans-omics” approach to scientific development. In their view, decoding the genome is part of a continuum of activities that includes epigenetics, proteomics, cell biology, systems biology and computer science.

Most importantly, perhaps, they see all these activities as integrated and dedicated to “advancing the science of medicine” and “improving the effectiveness of healthcare.” Clearly, they remain driven by the sense of urgency that allowed them to identify and decipher a deadly pathogen by sequencing its entire DNA sequence in three days.

I left BGI inspired by what I saw and heard. The BGI team seemed refreshingly unencumbered by the petty divisions and willful near-sightedness we too often encounter in science and society. They are pursuing a grander vision that I, too, have lost at times. More than ever, I am hopeful that with enough idealism, ambition and even a little chutzpah, Autism Speaks collaborations like this one will soon deliver a better future for all of our families.

After a few drinks and a dinner of simple and very spicy local fare in the BGI canteen, Yang leaned over to me and said matter-of-factly, “We’ll get it done.”

Please visit our science pages for more news and perspective.

Twin Study Suggests Environmental Role in Autism: Now What?

July 7, 2011 31 comments

Posted by Alycia Halladay, PhD, director of research for environmental science, Autism Speaks

As reported last week, a large twin study supported by Autism Speaks compared the frequency with which identical and fraternal twins both share a diagnosis of autism. This approach enabled the investigators to use statistical techniques to calculate the degree to which environmental factors shared by twins contribute to their risk of developing autism. Such factors include conditions in the womb and during birth.

The results of the California Autism Twin study were game-changing because they revealed a much larger environmental influence than had previously been estimated—accounting for about 58% of the risk of developing autism. By contrast, much smaller twin studies had previously suggested that genes largely accounted  for a child’s risk of autism.

The results underscore the need to investigate the role that non-inherited risk factors play in the development of autism spectrum disorders (ASD). So what’s being done to help speed this research? And what role are Autism Speaks and its donor dollars playing in this effort?

Autism Speaks has funded over $21 million in the study of environmental risk factors, an initiative we call (obviously enough) the Environmental Factors of Autism Initiative. Already, we have a large body of evidence suggesting that it is not any one environmental factor, but many different factors working together, that elevate the risk and severity of autism in individuals with a genetic predisposition for this condition. In other words, autism is seldom caused by any one thing and neither is it an “all or nothing” condition.  Furthermore, different combinations of genetic and environmental risk factors contribute to individual cases of autism.

Within the Environmental Factors of Autism Initiative are ongoing studies focusing on environmental exposures that occur before and during pregnancy and throughout the first year of life—crucial periods for human brain development. These studies look at such possible risk factors as maternal and paternal age, socioeconomic status, season of birth, exposure to chemicals or toxic agents, nutrition and exposure to various pharmaceutical drugs during pregnancy, the difficulty of labor and delivery, and various other forms of prenatal stress.  The researchers we support are also investigating the mechanisms by which genes and the environment may interact (so-called epigenetics) and the role of the immune system.  We are also supporting large scale epidemiological studies that focus on pregnancy and the first year of life.  These include the EARLI study  and the IBIS study.

Are you interested in learning more about the studies Autism Speaks is funding with donor dollars? We are proud to debut the new Grant Search function on our website. Please use it to explore past and present research studies by topic or location. And if you or your family is affected by autism, please consider participating in one of our clinical studies.

Meeting highlights environmental influences on genetic risk factors for ASD

March 15, 2011 19 comments

Everyone knows that some environmental factors can have adverse effects on health, especially early in development.  For example, we know that exposure to cigarette smoke is particularly bad for infants and young children, increasing risk for Sudden Infant Death syndrome, respiratory challenges and middle ear infections.  While we are still learning what kinds of environmental factors might impact the intricate process of brain development, and exactly how these impacts occur, we all want to know how environmental factors influence risk for autism.

Last week the Society of Toxicology met in Washington D.C. to discuss not only environmental effects, but how they may interact with our genes to confer autism risk.  The most popular topic of  this 50th anniversary meeting was epigenetics —literally changes made “above the genome”.   Different epigenetic changes have the effect of making the genetic code more or less available for reading and the production of  proteins.  In other words, the environment can actually turn off the functions of genes, resulting in downstream effects on brain and behavioral development.

During a special symposium organized by autism researcher Isaac Pessah, PhD from the University of California at Davis and Cindy Lawler, PhD at the National Institute of Environmental Health Science, , scientists discussed new data and examples of how environmental factors can lead to changes in autism risk.  Animal models of autism are essential for carrying out tests such as these, as different amounts of exposure to a particular substance can be carefully delivered and the outcomes observed with all other variables controlled.

Janine LaSalle, PhD at the University of California at Davis studied the effects of a flame retardant on behavioral development and cognitive function.  She and her colleagues showed that these cognitive effects, which are similar to those found in autism, are dependent on both the sex of the animal and proper function of epigenetic mechanisms that turn a collection of other genes “on” or “off”.

Researchers in the Tanguay lab at Oregon State University are using the humble zebrafish to study a newly discovered type of gene expression.  The research team is studying the effects of alcohol (ethyl alcohol, both the type found in beverages and and as a biofuel additive to gasoline) and a common acne treatment ingredient (retinoic acid, a metabolite of vitamin A ) on gene expression in the zebrafish.  They are finding that disruptions in this new type of gene expression (microRNAs) can have surprisingly large effects on the rest of the genome.

We know from many previous studies that duplications or deletions of collections of genes—called copy number variants or CNVs—can be associated with increased autism risk.  Scott Selleck, PhD, from Penn State University reported on his study which looked at the genetic background of children in the CHARGE study at UC Davis (http://beincharge.ucdavis.edu/).  Individuals with ASD showed increased lengths of CNVs at certain points in the genome. His lab reasons that these CNVs may be areas of what he calls “genomic instability” where environmental chemicals affect gene expression.   We need to know more about these CNVs and whether or not they are the reason some individuals are more susceptible to environmental factors in development.

Genes and environment interact, yes, but another important factor is when.  Timing of the environmental insult can be crucial.  Studies of neural stem cells are showing us that there exist critical periods in the development of these immature brain cells that include times in which cells divide, and also a later time when the immature cells become either neurons or another type of brain cell known as glia.  It is at these times when environmental influences might have their biggest effect.

Pat Levitt, Ph.D. from the University of Southern California spoke on how the combination of genetic vulnerabilities and  environmental factors can converge to disrupt brain development and function.  One example involves the MET gene, which controls the development of a special class of inhibitory neurons. Previous research showed mutations in MET to be associated with autism, especially in individuals with gastrointestinal dysfunction.

Dr. Levitt and his colleagues demonstrated that exposure to chemicals in diesel fuel exhaust also decreases proper expression of the MET protein.  This reduction in expression leads to changes in complexity and length of neurons as they reach to connect with other neurons.  These changes may contribute to the previously observed effects on brain development.  Interestingly, a recent report notes an increased risk for autism in children whose mothers lived within 1000 feet of a major highway during pregnancy.

Autism Speaks is actively supporting a number of research projects investigating the role of epigenetics in autism, including how environmental factors interact with genetic mechanisms to influence behavior.  A primary focus of research invited for submission to Autism Speaks in 2011 is the mechanism of gene/environment interactions, including epigenetics.

To read about all the research Autism Speaks is funding in this area, click here http://www.autismspeaks.org/science/research/initiatives/environmental_factors.php.

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December 14, 2010 IACC Meeting Summary

December 21, 2010 4 comments

The Interagency Autism Coordinating Committee (IACC) met on Tuesday, December 14, at the Bethesda Marriott in Bethesda, Md. This is the fifth time the Full Committee has met in 2010. The IACC has made significant progress in the past year in the following areas:  1) releasing the 2010 Strategic Plan for Autism Research (February 3); 2) publishing the 2008 Portfolio Analysis Report (January 19); 3) releasing the 2009 Summary of Advances in ASD Research; 4) hosting first annual IACC Services WorkshopBuilding a Seamless System of Quality Services & Supports Across the Lifespan (November 8); and 5) updating the 2011 Strategic Plan for Autism Research.

IACC Chair and NIMH Director Thomas Insel, M.D. opened the meeting with a presentation on research developments since the last IACC meeting. Dr. Insel reported that autism was a “hot topic” at the recent Society for Neuroscience meeting with a 30 percent increase in abstracts focused on autism. The meeting also included a Public Symposium, Autism: Progress and Prospects, chaired by Gerald Fischbach, M.D., Scientific Director, Simons Foundation Autism Research Initiative.

The IACC meeting agenda was devoted primarily to consideration of updates to the Strategic Plan for Autism Research. Members of the Strategic Planning Subcommittee presented the IACC with modifications to the existing plan with appendices of new research advances, funding gaps and new research opportunities for each section of the plan. The Committee approved most of the recommendations made by the Subcommittee.

The Subcommittee’s recommendations included objectives to better understand wandering and fever in persons with ASD to Question 2 of the plan.

The Committee voted to retain the title of Question 3, “What caused this to happen and how can it be prevented?” Updates to Question 3 include reference to a Workshop “Autism and the Environment: New Ideas for Advancing the Science,” held September 8, 2010, which was co-sponsored by Autism Speaks and NIEHS. The meeting involved environmental scientists who have successfully identified environmental risk factors for other conditions, such as Parkinson’s Disease, in an effort to develop better strategies for discovering environmental risk factors contributing to the etiology of ASD. The committee voted to accept new research objectives, including in the following areas: epidemiological studies that take advantage of special populations or expanded existing databases to inform our understanding of environmental risk factors for ASD, to include  adverse events following immunization (such as fever and seizures), mitochondrial impairment, and siblings of children with regressive ASD; and the role of epigenetics in the etiology of ASD, including studies that include assays to measure DNA methylations and histone modifications and those exploring how exposures may act on maternal or paternal genomes.

Recommendations for Question 4 were also accepted. These included research objectives to assess the effectiveness of interventions and services in broader community settings by 2015; to study interventions for nonverbal individuals with ASD; and to focus on research on health promotion and prevention of secondary conditions in people with ASD. Secondary conditions of interest include overweight and obesity, injury, and co-occurring psychiatric and medical conditions.

The IACC’s review of the Subcommittee’s recommendations for Question 5 included extensive discussion about how the IACC should address issues related to mortality, safety, and health within the IACC. New research objectives were approved to support research on health and safety issues leading to mortality.

The Question 6 recommendations on future needs of adults highlighted the urgent need for additional scientific research specific to this group. In 2010, several national advocacy groups devoted private resources to initiatives on adult services that have been brought to the IACC’s attention.

Finally, Question 7 is focused on the infrastructure and surveillance needs. The committee noted concern in funding availability for these needs. New research objectives were added. These included objectives to establish a robust network of clinical research sites that can collect and coordinate standardized and comprehensive diagnostic, biological (e.g. DNA, plasma, fibroblasts, urine), medical, and treatment history data that would provide a platform for conducting comparative effectiveness research and clinical trials of novel autism treatments; and to create an information resource for ASD service providers, researchers, families, and people with an ASD which serves as a portal to obtain the most recent evidence-based reviews and plans for intervention, services, and support.

“Public input has been critically important to the Strategic Planning process,” says Geraldine Dawson, Autism Speaks’ chief science officer and IACC member. “Based on feedback received from both consumer and professional stakeholders during the Request for Information phase, the recommended Strategic Plan will include new objectives that enhance the focus on environmental factors and lifespan issues affecting adolescents and adults living with autism.”

The afternoon session began with the Public Comments portion of the meeting. Ms. Idil Abdull, parent advocate and co-founder of the Somali American Autism Foundation, thanked the IACC for its decisive action on exploring the Somali autism issue and urged it to sustain this effort. Also presenting during Public Comments was Mrs. JaLynn Prince, President and Founder of the Madison House Foundation, based in Montgomery County, Md. The mission of the Madison House Foundation is to identify the lifelong needs of adults with autism and fill those needs through education, awareness, and advocacy. Mrs. Prince encouraged the IACC to explore the expertise of organizations like the Madison House which have been dealing with adult service issues in local communities throughout the country.

The agenda also included several updates on issues raised during recent meetings. At the October meeting, the IACC asked Autism Speaks, NIEHS and CDC to investigate issues raised concerning the Somali population in Minnesota. Coleen Boyle, Ph.D., Acting Director, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention and IACC Member, Cindy Lawler, Ph.D., National Institute of Environmental Health Sciences, and Autism Speaks’ chief science officer and IACC member Geraldine Dawson, Ph.D. provided an update on their efforts with respect to this issue. It was reported that collectively $350,000 has been committed to begin to study this issue, with Autism Speaks contributing $100,000 to this effort.

In response to a presentation on Wandering and Autism at the October meeting, the IACC created a subcommittee on safety issues the first task of which is to write the secretary of HHS on the recommendations that were made during the meeting. Lyn Redwood, R.N., M.S.N. Co-Founder and Vice President, Coalition for Safe Minds and Co-chair, Safety Subcommittee, and Alison Singer, President, Autism Science Foundation and Co-chair, Safety Subcommittee, reported on the Subcommittee’s recent meeting. The IACC authorized the Subcommittee to proceed with its information gathering in order to finalize the letter to the secretary. To inform this letter, the Subcommittee’s representatives will meet with the Departments of Education and Justice and will develop a Request for Information (RFI) on wandering. It was also announced that Autism Speaks and the Autism Science Foundation will fund a study utilizing the Interactive Autism Network (IAN) on this issue.

Services Subcommittee Co-chairs Ellen W. Blackwell, M.S.W., Centers for Medicare and Medicaid Services and Lee Grossman, President and CEO, Autism Society, reported on their Services Workshop on November 8 and subsequent subcommittee meeting. The goal of the workshop was to determine a set of recommendations to make for the Secretary of HHS. The Subcommittee is using slides from the workshop to inform the recommendations to be sent to the Secretary. The Subcommittee believes another workshop on services will be necessary next year.

Finally, the IACC solicited the input of IACC member Alan E. Guttmacher, M.D., Director Eunice Kennedy Shriver National Institute of Child Health and Human Development, on the implications of the proposed addition to Question 1 of the Strategic Plan to conduct five studies on the ethical, legal and social implications of autism screening research, including at least one study on the implications of potential future genetic testing. The committee agreed to look at what other diseases have done in this area and will convene a workshop next year.

The IACC is scheduled to meet again on January 18 and will finish its update of the Strategic Plan’s Introduction section at that meeting before approving the plan.

The importance of studying environmental factors in ASD

August 9, 2010 4 comments

Last week, the Senate Environment and Public Works Committee convened a panel of experts to investigate the role of environmental factors in autism spectrum disorders (ASD; link to web archive for video). Although genetic factors are known to contribute to the risk of autism, we also need to understand environmental factors and their interactions with genetic susceptibility.

The dramatic increase in autism prevalence over the last two decades—over 600% during this period—underscores the need for more research on environmental factors.  Our understanding of typical brain development combined with what we’ve learned from examining the brains of individuals with autism have focused efforts on the prenatal and early postnatal environment.  To investigate environmental factors that may be active during this time, researchers are casting a wide net on potential environmental agents that can alter neurodevelopment, including exposure to metals, pesticides, polybrominated diphenylethers and other chemicals.

Isaac Pessah, Ph.D., Director of the University of California, Davis, Children’s Center for Environmental Health and Disease Prevention, participated in the panel and said in his testimony, “We must identify which environmental exposures and combination of exposures are contributing to increased overall risk in the population and identify the most susceptible groups. Only by bringing together the concerted effort of multidisciplinary teams of scientists can we identify which of the >80,000 commercially important chemicals currently in production promote developmental neurotoxicity consistent with the immunological and neurological impairments identified in individuals with idiopathic autism”.

To help speed an understanding of environmental factors, Autism Speaks is supporting research on several fronts. In 2008, Autism Speaks launched the Environmental Factors Initiative to fund investigators researching aspects of environmental causes and autism.

A collaboration with the National Institute for Environmental Health Sciences (NIEHS) has resulted in a network of 35 international scientists who gathered at this year’s International Meeting for Autism Research (IMFAR) to promote collaboration, identify gaps in our understanding and foster opportunities for innovative research which is discussed in more detail in Dr. Dawson’s 2010 IMFAR recap.  This fall, Autism Speaks and NIEHS will co-sponsor a workshop to help identify the most promising strategies and scientific directions for understanding the role of the environment in ASD.

A large collaborative study which will pull together data from six international registries is being funded by Autism Speaks to explore early environmental risk factors for ASD.

Autism Speaks is also leveraging longstanding investments to make the best use of research resources that currently exist. For example, the Autism Genetic Resource Exchange (AGRE), a premiere genetic resource for scientists studying autism, is now collecting environmental data from families to pair with the genetic and medical data. Autism Speaks has partnered with the National Institutes of Health to fund the the EARLI and IBIS research networks to study environmental factors in infants at risk for autism. The EARLI network is following 1200 mothers of children with autism from the start of another pregnancy through the baby sibling’s third birthday. The IBIS network is charting the course of brain development in infant siblings of children with autism. Together with Autism Speaks, these groups are exploring both genetic and environmental risk factors for ASD.

Taken together, Autism Speaks’ investment in research on environmental factors promises to shed light on an important area of autism research that has until recently remained in the shadows.  We look forwarding to following the new directions illuminated by the discoveries made possible by these various research opportunities.

Categories: Science Tags: , , ,
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