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Keyword: ‘oxytocin’

Is oxytocin a safe treatment for autism?

December 7, 2010 1 comment

“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.

The hormone oxytocin is believed to play a role in social bonding and affiliation.  Researchers using animal studies have shown that oxytocin released in the brain regulates social recognition, social memory, mother-infant and male-female bonding, and other aspects of attachment.  Because social impairments are one of its most consistent features of autism, a number of scientists have hypothesized that abnormal oxytocin function might play a role in autism spectrum disorders (ASD).

The data regarding whether individuals with ASD have changes in oxytocin signaling are somewhat mixed.  A few studies have found children with ASD have lower average levels of blood oxytocin in comparison to typically developing children matched for age. Several  genetic studies have found associations between autism and specific forms of the gene for the oxytocin receptor.  Recently, it was reported that post-mortem brain tissue from individuals with ASD showed lower levels of gene expression for the oxytocin receptor when compared to age/gender matched comparison individuals.

So far only a few studies have examined the effect of administering oxytocin in human beings.  The data suggest that administration of oxytocin, either nasally or intravenously, positively impacts human social behavior.  For instance, recent studies with typical individuals show that giving oxytocin can increase gaze to the eye region of human faces, increase memory for faces, and improve the ability of people to infer the mental states of others (known as Theory of Mind).  All of these are challenges that have been associated with autism.

Given the lack of pharmacologic treatments for social deficits and the possibility of dysregulated oxytocin signaling in autism, many have proposed oxytocin as a treatment for ASD.  These studies are just beginning.  The three reports published so far have suggested that a single dose of oxytocin can temporarily improve social cognition in adults and, in one study, teenagers, with ASD.  In a pilot placebo-controlled study, researchers found that twice daily oxytocin in adults with autism resulted in some improvements in social function and quality of life and reductions in certain types of repetitive behaviorsThe data are very preliminary and larger follow-up studies are now underway.

Together these first studies support a potential role of oxytocin in ASD and suggest oxytocin could have therapeutic benefits for the treatment of ASD symptoms in adults, especially in the area of social functioning.  It is important to note that there are currently no published safety or efficacy data for oxytocin in children.

Autism Speaks is funding research to better understanding the role of oxytocin in ASD.  More information on clinical trials for oxytocin as a treatment for ASD can be found at

On the Cutting Edge of Treatment and Technology

July 15, 2011 14 comments

Posted by Rob Ring, PhD, vice president of translational research for Autism Speaks

Translational research in autism converts complex scientific discoveries into  real life benefits for those living with autism spectrum disorders (ASDs). Earlier this year, I had the privilege of organizing and moderating a translational research symposium we called “Autism Spectrum Disorders: From Genes to Targets to Treatments” at the New York Academy of Sciences. The symposium was made possible through funding from Autism Speaks. Indeed, sponsorship of meetings like this is an essential part of Autism Speaks’ commitment to advancing innovative autism research.

The New York Academy symposium brought together respected experts working on translational autism research from the proverbial bench to the bedside. The day was filled with stimulating scientific discussion that helped those of us involved in this research to align our research priorities.

In this week’s “Science in the City” podcast from the New York Academy (click the image below to access the podcast), you can listen in as two of the symposium’s speakers offer a behind-the-scenes look at the new technologies and treatments that could redefine how we understand autism. Eric Hollander, of the Albert Einstein College of Medicine, talks about using oxytocin, a brain chemical that fosters social bonding, as a potentially treatment for aspects of autism. And Timothy Roberts, of the Children’s Hospital of Philadelphia, discusses his use of brain imaging to identify early markers of autism—such as a tell-tale delay in how a child responds to voices and other sounds.

For more information about the translational research Autism Speaks funds, please visit our Grant Search portal, where you can learn more about specific studies on technology development, biomedical interventions, and more.

We’d love your feedback. So please leave a comment and respond to our polldaddy question of the day below the podcast link. Thanks.

Click the image to hear the podcast.

Social skill in a pill?

June 9, 2011 19 comments

As we learn more about the unique behaviors of different animal species and how circuits in the brain control those behaviors, we will come upon more options for treating brain-based disorders.  In the case of autism spectrum disorders, a surprising potential treatment for social challenges emerged from the little-known prairie vole. The new research was published in April online in Biological Psychiatry and supported by Autism Speaks.

Prairie voles may resemble pet store hamsters, but their ordinary appearance obscures unique behavior.  These voles are among the 5% of all mammals that are monogamous—that is they form a mating pair that remains for the life of the animal.  Contrast this seemingly virtuous performance with a similar species—the meadow vole—that engages a much more promiscuous mating strategy.  For each animal, the chosen mating strategy makes sense in terms of available mating partners and other environmental pressures. However, these mating strategies also produce consequences in terms of the animal’s “social skills” and the neural circuits which serve these behaviors.

Prairie vole females, who mate for life, are relatively picky.  So, when introduced to a new male, not surprisingly, female prairie voles tend to a be careful—wanting more than just a single visit before choosing her mate. This situation affords researchers an opportunity that Larry Young, Ph.D. at Emory University exploits in the partner preference task.

The partner preference task enabled researchers to dissect the social learning that occurs in voles soon after meeting.  A female prairie vole is paired with a male for up to 24 hours so they can meet, but not mate.  During this time, researchers can give the voles different drug compounds to manipulate this first date in various ways.  From the sensory cues, to the rewarding squirts of neurotransmitter, Dr. Young and his colleagues are learning the essential ingredients for effective social learning.

The first essential ingredient is oxytocin.  This well-studied hormone is involved in birth and lactation and has more recently been shown to enhance the much more subtle social perception of trust in humans. Oxytocin administration has also been shown to increase the amount of gaze to the eye region of a face in individuals with autism.

Pair bonding in the prairie vole requires oxytocin.  The brain regions that bind this hormone are closely associated with areas of the brain that signal reward and the “reward neurotransmitter”, dopamine.  In fact, if the brain binding sites for dopamine are blocked by a competing chemical, pair bonds between prairie voles do not form.  This result reveals that the reward system must actively participate for these strong social bonds to form.

Recall the very similar-looking but very differently behaving vole called the meadow vole.  What creates their very different patterns of social engagement in these two species?  Dr. Young and colleagues showed that the distribution of receptors for the hormone oxytocin was a primary difference between the two species of animals.  In fact, female meadow voles that were made to express oxytocin receptors in a prairie vole pattern began behaving just like prairie voles with regard to mating behavior.  The promiscuous voles became monogamous by changing the expression of receptors in the brain.

This background would seem to be an elaborate set up to discuss the drug that makes the difference, but the value that these animals bring to research can not be underestimated.   The overt differences in behavior led to the discovery of hidden differences in brain physiology, which can be manipulated using drugs to improve the lives of humans.

Using a compound called d-cycloserine (DCS) the research team was able to enhance the cognitive processes involved in developing a partner preference in prairie voles. The changes are likely due to two factors:  1) an enhancement of the sensory cues that accompany a social interaction, which are primarily smell-based for rodents.  2) a boost of the memory of the social interaction, so that the partner will be recognized and associated with a positive encounter when they next meet.  The dose of DCS matters as only a low dose—one that increases glutamate neurotransmission—elicits a bias for choosing the previously met partner over the stranger.  Higher doses of DCS have a different effect on the receptor causing an overall reduction in glutamate transmission and providing no bias in the partner preference task.

What is the relevance of this to autism?  Imagine if one were able to enhance the interest of social stimuli prior to a therapy session.  Could the sort of compounds Dr. Young and his colleagues are investigating be beneficial when used in addition to behavioral therapy for helping individuals on the spectrum focus develop healthy patterns of social engagement?  In an preliminary study published in 2004 by a different group of researchers, DCS decreased social withdrawal in individuals with ASD as measured by the Aberrant Behavior Checklist.  Dr. Young and colleagues continue their research with DCS and other compounds that improve the salience of social features of an environment.  We look forward to seeing more of these results translate into meaningful treatments for people as this research direction progresses.

Autism in the News – Tuesday, 01.04.11

January 4, 2011 2 comments

Scientists Test ‘Trust Hormone’ For Autism Fight (National Public Radio)
For decades, parents of children with autism have been searching for a drug or diet to treat the disorder. Their latest hope is the hormone oxytocin. It’s often called the trust hormone or the cuddle hormone. And just to be clear, it has nothing to do with the narcotic oxycontin. Read more.

Apple iPad, iPod Touch might help people with autism take steps toward independence (
With a simple touch, Marc Rader knows what comes next in his day. The 13-year old taps the tablet computer screen, and a picture of the kitchen sink pops up, accompanied by his mother’s voice. Read more.

Families Have Mixed Reactions to New Autism Insurance Mandate (Fair Grove, Mo.)
A number of Missouri children are now eligible for insurance coverage of their autism therapies. That’s because a new Missouri law requires insurers to cover $40,000 a year of applied behavioral analysis for children through age 18. Read more.

With support, ‘positive outcomes’ possible for those with autism (Monmouth, N.J.)
Tabitha Cooper was diagnosed with Asperger’s syndrome on Sept. 11, 2004 at the age of 23. Her diagnosis explained a lot of the struggles she’d battled in high school. Cooper said she wasn’t diagnosed when she was younger because many people thought autism was a mental disorder. Read more.

New Law Expands Services for KY Children with Autism (Frankfurt, Ky.)
The New Year brings Kentucky a new law that requires insurance companies to cover the diagnosis, treatment and therapies of children with autism. Former state representative Scott Brinkman of Louisville, who is the father of a 26-year-old son with autism, sponsored the legislation. Read more.

Autism insurance mandate begins with new year in Missouri (Jefferson City, Mo.)
Several thousand children will become eligible for insurance coverage of their autism therapies as a Missouri law takes effect Saturday. For thousands of others, their parents will continue to have to pay out of pocket or simply forgo the costly treatments. Read more.

How do we study the brain?

August 2, 2010 4 comments

This is a post by staff blogger Daniel Lightfoot, Ph.D., Director of the Autism Tissue Program.

Autism is a clinically diagnosed disorder. Much of our knowledge about autism comes from direct interactions with people diagnosed with autism spectrum disorders (ASD), listening to parents of children on the spectrum, and conducting clinical studies. Magnetic Resonance imaging (MRI) studies have added to our understanding by giving us a peek at the autistic brain and structural differences that may be present.  Additionally, strong efforts in genetic analysis have discovered genes of interest and regions within our DNA that may play a part in the development of ASD. Though all these efforts have taught us much about autism, we still know relatively little about the autistic brain and why its development is altered.  So how do we learn more?

We must look at things directly.

Consider the following analogy.  If you were told to study an office building, but could not go inside, you may find yourself walking around the structure and studying its shape.  You could interact with the building by touching the stone and steel that form the building. This would be analogous to clinical and behavioral observations typically made of individuals with autism.  Engineering plans, may tell you what the building is comprised of (analogous to genetics studies) and even how it is shaped on the inside—where the rooms are and how stairs, elevators and hallways connect them. This last approach would be analogous to structural MRI studies. Despite the value of each of these perspectives, none of these examinations could reveal the happenings within the building.  You would know nothing about the people working within the building, what they were doing, how they interacted with each other and what their jobs may have been.

In a similar way this is how we most often study autism, by looking at the outside, taking an indirect perspective.  But there are some scientists who look at things differently.  They go inside the building.  They study brains directly.  And what some of these exceptional scientists have learned so far is quite astounding.

Studying brain tissue directly from deceased individuals, enables researchers to look microscopically at the cells within human brains, how these cells are connected with one another, how they are structured on a molecular level and what that most interesting of molecules – DNA – is doing within the cell. Studying the brain directly allows a far more thorough level of research to be conducted; enabling researches to ask and answer questions that otherwise could not have been addressed, to study the cell and molecular bases behind autism, and granting the ability to look at the fundamental underpinnings behind ASD. Scientists need to study brains from both affected and unaffected individuals in order to make informative comparisons.  Without both affected and unaffected individuals to study, the brain tissue loses context and is far less instructive.

Recent breakthroughs in brain tissue research

With brain tissue, scientists can look at the many components needed to make and organize proteins within a cell for proper brain function.  Investigators have explored genes that synthesize a major inhibitory transmitter (GABA) in the neural cells and found decreased activity in a special type of protein called an enzyme. In addition, other molecules that detect and bind to GABA (called receptors) are decreased in prevalence in several brain regions. Enzymes and receptors are targets for therapeutics (drug intervention) and are therefore important to understand.

A report investigating 26 brains from the Brain Atlas Project describes some of the atypical findings in the brains of individuals with autism: namely defects in the production, development and organization of new neurons in the brain.  Using digital images available to researchers from the Brain Atlas Project, investigators showed that cell populations in the brain, organized in distinct patterns termed minicolumns, are more numerous in the autism brains.  Scientists postulate that this increase of minicolumns results in higher sensitivity to stimuli coming into the brain, but at a cost to processing and output in the form of behaviors that characterize autism.

Brain tissue evaluation of mitochrondria reveals differences in these critical cell powerhouses. Mitochondria are responsible for producing most of the energy inside a cell.  Brain tissue research has revealed defects in mitochondrial proteins important for shuttling molecules across brain cell membranes. Much like a battery, controlling the flow of molecules within different compartments of a cell is one of the key components to the energy production process and one that appears to be functioning differently in individuals with autism.

Oxytocin is a hormone with a role in social recognition, pair bonding, anxiety, and maternal behaviors. Brain tissue research provides evidence of oxytocin receptor deficiencies resulting in a lower level of effectiveness. This means that even if the hormone is produced normally, it has a reduced effect.  Treatments to increase oxytocin functionality in the brain are being explored and brain research will continue to contribute to the understanding of the role of this hormone in the brain.

Scientists also use brain tissue to explore findings from other medical assessments.  Analysis of cerebral spinal fluid (CSF) from subjects with autism has shown immune markers of neuroinflammation.  Immune activity found in cells from the brain support the concept that specialized brain cells that respond to infection or damage are active in autism brain samples.

How you can help

Unfortunately, brain tissue is exceptionally rare, thereby hindering this rigorous approach to understating autism

The Autism Tissue Program (ATP), a clinical program of Autism Speaks, is dedicated to supporting scientists worldwide in their efforts to understand autism, autism related disorders and the human brain.  The ATP makes brain tissue available to as many qualified scientists as possible to advance autism research and unravel the mysteries of this and related neurological conditions.  In fact, it is the only program solely dedicated to increasing and enhancing the availability of post-mortem brain tissue for basic research in autism.  You can make a profound difference to all those who struggle with autism by registering as a brain tissue donor with the ATP.

A large part about why we, at the ATP, keep working is that when people with autism die, it is sometimes unexpectedly and with little to explain the cause of death.  Detailed analysis of the donated tissue helps provide answers as to why death occurred and helps us learn more about these unique individuals in addition to helping researchers understand autism.

If you are the parent of a child or children with an autism spectrum disorder, are related to a person with an autism spectrum disorder, have autism yourself or are unaffected, your donation can greatly affect our progress in understanding autism.  We encourage entire families to consider donations of brain tissue for research.

While in some states and countries, registration for organ donation makes the process automatic at the time of death (as on your driver’s license), this is not the case for brain tissue donation.  Because brain tissue is used for research and not transplantation, it is not included on most organ donation registries. Therefore, by registering with the ATP, you declare your intent to donate brain tissue as well as making your wishes known to your family in a formalized way.  However, registration does not make tissue donation automatic at the time death.  This final choice of donation is made by your next-of-kin, which in legal terms, is defined in this order: spouse, adult children, either parent, adult siblings, or guardian at the time of death.  Should you choose to become an ATP registrant, and wish to donate your brain upon death, to the ATP in support of autism research, we encourage you to inform others of your wishes, including your immediate and extended family.  Helping your friends and family learn more about the ATP and its mission will help them understand your unique choice.

For more information about the ATP and becoming a registered donor, visit our site at www.autismtissue


What is the value of combination therapies in autism?

April 26, 2010 3 comments

This Top 10 Research Achievements of 2009 post comes from guest blogger Evdokia Anagnostou, M.D., a Clinician Scientist at Bloorview Research Institute and an Assistant Professor, Department of Pediatrics at the University of Toronto. Dr. Anagnostou leads a program of experimental therapeutics and neuroimaging in autism and is leading a series of clinical trials to study the efficacy of oxytocin, memantine, and other compounds for symptoms associated with autism.

The last decade has been fairly productive when it comes to research in psychopharmacology.    Large scale multicenter studies have been conducted and more than one medication has shown benefit for the treatment of symptoms associated with autism.    Still, our approach to pharmacology research has been relatively limited. We have examined the similarities between symptoms associated with autism and symptoms in other disorders, assumed  that similar symptoms across disorders have similar neurobiology, and “borrowed” medications from other disorders with “overlapping “ symptoms to test in autism.  The approach has been somewhat successful.  We now have evidence from large multisite studies to support the efficacy of some atypical antipsychotics for irritability and aggression (risperidone (1) and aripiprazole (2)), and stimulants for the treatment of ADHD-like symptoms (3).  This approach also has its limitations.  An example may be the failure of large multisite studies to show effectiveness for the treatment of repetitive behaviors for serotonin re-uptake inhibitors (SSRIs). Although much remains to be explored and many questions still remain, one cannot help but wonder whether it is time for a paradigm shift in the way we approach pharmacology research.  There are plenty of approaches that still remain to be tested in this population.  Firstly, we have not yet done truly translational work.  In other words we have not yet used the findings from genetics/ animal models/ pathology to develop treatments based on the neurobiology of autism itself, as it is revealing itself to us over the past few years. Secondly, we have not addressed what we really do in real life which is combine medications with psychosocial interventions.  In fact, we have no data to date that any of the medications we use actually treat autism. Medications do not teach skills. It is the psychosocial interventions that treat autism.  What we attempt to do with medications for the most part, is to enhance learning from such interventions either indirectly by reducing behaviors that interfere with learning ( e.g. irritability, aggression, hyperactivity, repetitive behaviors) or by directly facilitating learning processes (potential examples in trials: memantine, oxytocin).  The question remains whether the combination of medications with psychoeducational treatment is favorable compared to medications alone or the psychoeducational treatment alone. Previous studies in other neurodevelopmental disorders, such as ADHD, (4) have taught us that when the effect of medication is large, it may be hard to show additional benefit from psychosocial interventions.  As such both comparisons: combination treatment vs. medication, and combination treatment vs. psychosocial intervention are worth exploring.

Recently, the RUPP group published the first randomized controlled trial that tested the combination of a medication with a parent training curriculum based on ABA principles for the treatment of irritability/aggression (link to Top 10 story on combination therapy) (5).   This was a 24 week randomized trial of combination treatment vs. medication only (risperidone/aripiprazole alone).  124 children ages 4-13 with frequent aggression, self injury and tantrums were recruited.  The primary outcome measure was a modified for autism version of the Home Situations Questionnaire (HSQ), a 20 item questionnaire aimed to measure non compliance in every day circumstances. Secondary measures included the Aberrant Behavior checklist, the Clinical Global Impressions measure and the Children Yale Brown Obsessive – Compulsive Scale-PDD version.  The parent intervention consisted of 11 sessions with a certified therapist, three additional optional sessions and up to 3 booster session for a total of up to 17 sessions, lasting 60-90 min and delivered individually to the families. The curriculum included teaching on visual schedules, positive reinforcement, compliance, functional communication and adaptive skills.  The sessions were fairly individualized to the child’s level and needs. The medication was risperidone dosed by weight and was switched to aripiprazole by week 8 if the risperidone was ineffective.  The study reported that combination treatment was more effective than medication alone as measured by the HSQ, irritability hyperactivity and stereotyped speech as measured by the ABC. They also reported that the mean dose of medication required in the combination group was less than that required in the medication alone group (1.98 mg/d vs. 2.26 mg / day respectively).

In summary, combination treatment was more effective at improving everyday outcomes than medication treatment alone.  This Top 10 paper provides initial evidence that such trials are feasible and worth exploring. The authors argued that this study aimed at a different outcome (real life situation improvement) than the original risperidone studies, and as such, suggests that integrated trials can be successful when the outcome measure for the medication is somewhat different than that for the psychosocial intervention / combination treatment.   In fact, as previously discussed, it makes sense that generalizability of the medication effect is accomplished by parent training given that the medication itself is not likely to teach the child or the family any skills.  The question still remains in the blogger’s mind whether the effects of combination treatment should be tested against intensive parent training alone. Although I agree with the authors that the effect size of the risperidone is large, these medications are associated with a relatively unfavorable side effect profile and it would be of great interest to learn how much of the effect size observed with the combination treatment can be achieved by using parent training alone, given that decisions on the using a medication are not solely based on the efficacy profile of medications. Such studies may have implications for systems delivery and the generalization of results may be more difficult given the differential insurance coverage for medications vs. psychosocial interventions, but may have significant impact in the way we treat children with autism

The study is very important as it is the first such trial in autism and highlights the need for integrated medication/psychosocial intervention trials. Future studies will likely focus on integrated treatments targeting both decrease of maladaptive behaviors as well as skills acquisition.

1. Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavior problems. N Engl J Med. 2002;347:314Y321.

2. Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Carson WH, Findling RL. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics. 2009 Dec;124(6):1533-40.

3. Research Units on Pediatric Psychopharmacology Autism Network. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry. 2005 Nov;62(11):1266-74.

4. MTA Cooperative Group. National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit/hyperactivity disorder. Pediatrics. 2004 Apr;113(4):754-61.

5. Aman MG, McDougle CJ, Scahill L, Handen B, Arnold LE, Johnson C, Stigler KA, Bearss K, Butter E, Swiezy NB, Sukhodolsky DD, Ramadan Y, Pozdol SL, Nikolov R, Lecavalier L, Kohn AE, Koenig K, Hollway JA, Korzekwa P, Gavaletz A, Mulick JA, Hall KL, Dziura J, Ritz L, Trollinger S, Yu S, Vitiello B, Wagner A; the Research Units on Pediatric Psychopharmacology Autism Network. Medication and Parent Training in Children With Pervasive Developmental Disorders and Serious Behavior  Problems: Results From a Randomized Clinical Trial. J Am Acad Child Adolesc Psychiatry. 2009 Oct 23. [Epub ahead of print]

Many journeys to the same location – methods that 21st century scientists are using to identify genes that cause autism

April 15, 2010 11 comments

We have asked several scientists who gave presentations at the April 10-11 DAN! conference in Baltimore to share their research and perspectives from the meeting with you here on the blog.  The following piece is from Dr. Simon G. Gregory, Ph.D. Dr. Gregory is an Associate Professor in the Center for Human Genetics, Duke University Medical Center His primary area of research involves identifying the complex genetic factors that give rise to cardiovascular disease and multiple sclerosis, Dr. Gregory’s group is also applying high-resolution genomic arrays to the discovery of chromosomal abnormalities and identification of epigenetic factors associated with autism.

For decades scientists have relied on traditional genetic approaches to identify genes that contribute to the development of autism. These approaches have included collecting extended, multi-generation families that contain one or more individuals with autism. Once a sufficient number of these families have been collected, hundreds of DNA markers that can highlight differences between us all at a genetic level (a bit similar to DNA fingerprinting used in CSI) are used to identify a region of the genome is linked with the disorder in the families. More recently, higher resolution technologies that benefitted from the completion of the human genome project have been developed to allow us to look at hundreds of thousands of markers simultaneously. This approach differs from the family-based approach in that it uses thousands of unrelated cases and age/sex/ethnicity matched controls. Together, both approaches have been successful in identifying genes, or at least regions of our chromosomes, that play a role in the development of autism. However, we know that many more genes will likely contribute to autism spectrum disorders (ASDs) and that not all mechanisms that disrupt the normal function of a gene will be based on a single DNA mutation or a variant present in the general population.

My group at the Duke Center for Human Genetics recently embarked on a journey to identify autism genes using an approach that looks at chromosome content, and yet we reached an interesting finding using another technique that doesn’t rely on the sequence of our DNA. For many years it has been known that ASDs can be caused by loss (deletion) or gain (duplication) of chromosomes. These genomic rearrangements can be large or small and some have been shown to cluster in particular regions of the genome, for example on the long arm of chromosome 15 (15q11-13). Our journey began by assessing the genomic content of 119 unrelated autistic children from families that we had collected over a number of years. We used genomic microarrays (microscope slides with printed content spanning our genome) to identify novel or common regions of deletion or duplication within one autistic child from each family. Although we identified a handful of novel regions and confirmed dozens of rearrangements that have increasingly been shown to exist within the ‘normal’ population, we decided to focus on a single deletion in one individual. The deletion, which contained five genes, sparked our interest because one of the genes, the oxytocin receptor (OXTR), had been previously implicated in autism. Previous studies using the traditional genetic approaches (mentioned above) had shown that OXTR was genetically associated with autism, other studies had shown that levels of oxytocin (a neurotransmitter that the receptor binds to OXTR) is important for pro-social behavior and that a knock-out of the receptor in mice can affect this behavior, and very recent studies have tested the supplementation of oxytocin in adults with autism.

After identifying the deletion in the one affected child we screened his family to see if it was novel and causative of his autism, or if he inherited the deletion from his parents. Somewhat disappointingly, his mother also had the deletion, but interestingly she had self reported obsessive compulsive disorder (OCD) for which OXTR has also been implicated. Although we could have stopped the journey at this point, we decided try a different approach. Previous studies have shown that OXTR is controlled in the liver by a chemical group (methyl –CH3) that sits on top of the DNA but which doesn’t change its sequence (click here for more information on epigenetic changes as they relate to autism). The phenomena of DNA methylation is a normal mechanism by which our cells silence parts of the genome that they don’t want to be active (mainly repeat and retro-viral sequences) but they also use it as a switch to turn on or turn off genes for protein production. Significant in our journey was that the child with autism who had the OXTR deletion also had an affected brother. This is significant because when we assessed the methylation status of the whole family we noticed that the affected brother has very high levels of methylation in five different CG bases (among the A’s C’s G’s and T’s of our genome where the methyl group resides) in a 1,600 base pair window that had previously been identified as being methylated in the liver OXTR.

Differential methylation isn’t a novel finding as a possible cause of autism. Previous studies in Rett syndrome, which has ASD like symptoms, have shown that mutations in the methyl CpG binding protein 2 (MECP2) gene not only contributes to the development of Rett syndrome but that these mutations affect the normal functioning of the gene which regulates the expression of other genes by altering their DNA methylation state. Additionally, imprinting (the silencing of a maternal or paternal copy of a chromosome by DNA methylation) has also been established as the basis for the development of Angelman and Prader-Willi syndromes that, again, have ASD like symptoms. Our next step was to validate the observation that increased methylation of OXTR in the affected brother may be a causal mechanism of autism. We expanded our analysis to include evaluation of the methylation status of OXTR in the peripheral blood of 20 controls and 20 individuals with autism, and in a second dataset of the post-mortem samples of temporal cortex tissue (a center for language and learning) in eight controls and eight children with autism. In both datasets we were pleased to see that the individuals with autism had higher levels of methylation than the controls. We next measured the level of gene expression of OXTR because we would expect that increased DNA methylation would result in decreased gene expression – which it did in a very small number of samples that we could test.

So you’re asking yourself, how, if all these other studies had pointed to OXTR being implicated in autism, is this discovery significant? Well, we hope that we have found a unique autism-associated DNA methylation signature in a receptor for a neurotransmitter that is important in social cognition in autism. The next more exciting journey will be to substantiate what we have found in a larger number of samples and to establish if oxytocin treatment can help

Autism in the News – Wednesday, 2.17.10

February 17, 2010 Leave a comment


Autism: Oxytocin Improves Social Behavior of Patients, French Study Finds (Science Daily)
Autism is a disease characterized by difficulties in communicating effectively with other people and developing social relationships. A team led by Angela Sirigu at the Centre de Neuroscience Cognitive (CNRS) has shown that the inhalation of oxytocin, a hormone known to promote mother-infant bonds and social relationships, significantly improved the abilities of autistic patients to interact with other individuals. Read more.


Turning Pointe raising funds to build autism academy (Chicago, Ill.)
Like most parents, Randy and Kim Wolf want the best for their son Jack. They want to give him opportunities to succeed, both academically and socially. Read more.

Special education funding falls short, Toronto board says (Canada)
Despite a drop in enrolment, Toronto’s public school board says it has more special education students than ever — and inadequate funding from the province to provide programming for them. Read more.


Immigrants struggle with declining health (Canada)
Some healthy people who immigrate to Canada find their health deteriorating after their arrival — an issue immigrant communities are struggling to understand and address. Read more.


Missouri House endorses bill mandating autism insurance (Jefferson City, Mo.)
A mandate for insurers to cover treatment for autistic children has cleared an important hurdle in the Missouri House. Read more.

Colo. recognizes people with disabilities (Denver, Colo.)
Today, hundreds of individuals with disabilities, family members, direct-support professionals and other service providers will descend upon the capital in Denver. Read more.

Autism Treatment Coverage Bill Passes VA Senate (Richmond, Va.)
The Senate has overwhelmingly passed legislation that would mandate coverage for an effective treatment for small children who have autism. Read more.


Coffee shop becomes home for mentally disabled children (Vietnam)
Tam became speechless trying to talk about her indescribable joy the first time she saw her grandson, suffering from Down’s syndrome, carry a tray of drinks to a customer and not forgetting to say “please have a drink, uncle.” Read more.

Race/walk to benefit UF Center for Autism and Related Disabilities (Gainesville, Fla.)
The third annual STAR 5K Race/Walk benefitting the University of Florida Center for Autism and Related Disabilities will be held Saturday. Read more.

Autism camp offered April 9 – 11, registration ends March 2 (Boone, N.C.)
Crinkleroot Retreat, a free respite day camp to be held April 9-11, is recruiting campers ages 8 – 14 with Autism Spectrum Disorders. The retreat will be held in Valle Crucis at Camp Broadstone and is staffed by trained Appalachian State University volunteers. Read more.


Autistic adults pose challenge (Ariz.)
Several of Arizona’s leading real-estate groups have tackled a growing national housing problem in a new report, Opening Doors: A Discussion of Residential Options for Adults Living With Autism and Related Disorders. Read more.


All for Animals Sets Up “Cuddles Fund” (Santa Barbara, Calif.)
When Bonnie Crowe received a Shih Tzu puppy from The Miracle Run Autism Foundation in 2008 as a therapy dog for her then 9-year-old autistic son, Jakob, she hoped things were finally turning around for her family. After all, the Agoura Hills resident had weathered Jakob’s autism diagnosis when he was two, she has a younger daughter with ADD and her husband was laid off from his job over a year ago… Read more.

Luke Faint paints up a storm (Australia)
Budding artist Luke Faint has picked up an art award in his first competition since taking up painting a year ago. Read more.

Autistic boy’s family wins fight to keep car (UK)
A Lincoln family who faced losing the only mode of transport for their autistic son have won a battle to keep their car. Read more.

Braddock father isn’t autistic, judge rules (Alleghany County, Penn.)
An Allegheny County judge Tuesday determined a Braddock man accused of abandoning his toddler daughter to die in freezing temperatures is not autistic, clearing the way for prosecutors to seek the death penalty against him. Read more.

Colby ready to fly (Australia)
If you’ve seen a young boy whizzing past you on a bike with a huge smile plastered on his face, it could have been Colby Matthews. Read more.


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