2012: The Year in Science

Date: 
January 03, 2013

2012: The Year in Science

A letter to the community
from Autism Speaks Chief Science Officer

 

 

Dear friends,

As we begin the New Year, I want to reflect on autism research advances made in 2012 and share some of the highlights with you. (Please also see our Top Ten Advances in Autism Research.)

This month marks the start of Autism Speaks eighth year. During this time, we’ve witnessed a dramatic increase in scientific publications on autism spectrum disorder (ASD) – an increase that’s outpaced research in other areas of health science. In 2012 alone, there were over a thousand. Most focused on understanding the biological basis of ASD. According to an analysis by the Interagency Autism Coordinating Committee (IACC), research on treatments and risk factors tied for second place in autism publications last year.1

Changes in Diagnosis and Prevalence

DSM-5

Throughout the year, controversy brewed over changes in the American Psychiatric Association’s criteria for diagnosing autism. (See our coverage of the issue here.) Last fall, field trials tested the new diagnostic system, which collapsed the previous subtypes of autism into one broad category called “autism spectrum disorder.” The field trial results showed that clinicians use the new criteria with more consistency than the old criteria.2 Although these results are encouraging, Autism Speaks is advocating for and funding its own research to better understand how the new criteria influence diagnosis, access to services and prevalence estimates. We want to make sure that the new system doesn’t exclude anyone from services who needs them.

Increasing prevalence spurs need for earlier screening and diagnosis

The Centers for Disease Control and Prevention (CDC) updated its prevalence estimates for autism in 2012.3 The new estimates indicate that ASD affects 1 in 88 children in the U.S. (1 in 54 boys). This represents a 78 percent increase from the 2007 estimate of 1 in 150. These alarming numbers demand immediate attention and resources from the U.S. government. In particular, we need increased research funding, services and supports, a point highlighted by Bob Wright in a Senate hearing on autism held last fall. (See news story here.)

A key finding in the new CDC prevalence report is that the average age of diagnosis remains between 4 and 5 years of age, despite the great strides in early detection and diagnosis made in recent years. To address this gap, Autism Speaks launched a new campaign to reduce the age of diagnosis and early intervention. This new effort also addresses findings of significant disparities in diagnosis based on gender, race and ethnicity.4 Our efforts to reduce the age of autism diagnosis will target underserved families from rural and ethnic minority backgrounds.

Meanwhile, researchers have developed autism screening questionnaires that can be used in a clinician’s office for infants as young as 12 months.5 These are now being tested and validated. Also in 2012, research demonstrated new early indicators of autism. They include unusual patterns of attention fixation and vocalizations.6 Scientists also are discovering early biological markers that indicate risk for autism. One 2012 study revealed distinctive early brain changes in infant siblings of children with autism who themselves went on to develop ASD. (The researchers used a MRI technique called diffusion tensor imaging.) These changes could be seen by 6 to 12 months of age, before the onset of the full syndrome.7 Among the infants who later developed autism, the changes included differences in the development of brain fiber tracts that help different regions of the brain communicate and function in a coordinated manner.

Still other work published this past year suggests that electroencephalography (EEG) may be a promising technique for identifying infants who will later develop ASD. Researchers found that atypical EEG patterns in response to social stimuli can help predict which infants will develop ASD.8

The Costs of Autism

In 2012, Autism Speaks released a new economic analysis of the cost of autism. This was vitally important as the old calculations, published in 2007, clearly underestimated this burden. The new analysis shows that autism now costs the U.S. about $137 billion annually, with much of the expense related to adult care. The same economic analysis associated greater intellectual disability with greater costs. Thus, early intervention that can increase cognitive abilities will help reduce autism’s financial burden on families and society.

To drive this point home, Autism Speaks is currently funding further economic analysis to calculate the lifetime cost-savings of providing early intervention. We hope that this information will help legislators understand that early intervention not only improves lives, it saves money.

Such savings can be redirected toward much-needed support services, especially those that increase employment and residential housing. A disturbing report this past year showed that, in the first two years after high school, over half of young adults with ASD are neither employed nor enrolled in higher education.9 This transition from adolescence to adulthood is a crucial time for providing supports and services that can shape the trajectory of adulthood for people with ASD.

Although we are making strides in passing legislation that supports insurance benefits for behavioral interventions, another 2012 study confirmed that families still bear great economic burdens.10 Investigators found that, on average, mothers of children with ASD earn 35 percent less than mothers of children with other health conditions. Family earnings averaged 21 percent less, often because one parent quits work to provide care. Advocating for appropriate healthcare insurance continues to be a high priority at Autism Speaks.

Understanding Risk Factors

We are inching closer to understanding the causes of autism. Based on studies published this past year, researchers now estimate that as many as 1,000 genes contribute to ASD risk.11 Mutations that contribute to autism risk can be inherited or arise spontaneously. These gene mutations, although rare in the general population, are not necessarily specific to autism. Some likewise contribute to risk for epilepsy, intellectual disability and other related conditions.

Although the great number of risk genes implies great complexity, they also have important clinical implications. First, there is the potential to correct some of the metabolic abnormalities produced by certain autism risk genes. For instance, investigators found that some rare genetic mutations associated with autism are necessary for metabolism or synthesis of an essential nutrient such as carnitine or branch-chain amino acids. (See our related news coverage here and here.) These types of autism might be prevented or treated through nutritional supplements.12

Second, some of the mutations associated with autism provide opportunities for early diagnosis, especially among high-risk infants with older siblings who are on the autism spectrum. The identification of these risk genes can encourage close monitoring of early symptoms so that intervention can begin as soon as possible.

Third, knowing whether a risk gene is inherited or spontaneous (“de novo”) can help inform adult family members of their children’s risk for autism. This, too, can flag the need for close monitoring during infancy.

Fourth, scientists have discovered that the autism risk genes identified so far converge on a few common biological pathways. Many of these pathways regulate how neurons (brain nerve cells) communicate with each other.13 Other risk genes appear to influence the development and function of the immune system.14 Scientists are focusing now on identifying biomarkers that can identify the subtypes of autism most likely to benefit from particular treatments. For example, research suggests that certain blood-based biomarkers reflect different patterns of gene expression.15

Another 2012 study identified a subtype of ASD involving regression, gastrointestinal (GI) problems and immune abnormalities.16 These and other genetic discoveries have increased interest in therapies that can restore the normal functioning of the brain pathways affected by autism risk genes. Already, several new treatments are being tested in animal models of autism, some of which demonstrate dramatic reversal of autism symptoms.17

To encourage investment in the development of such treatments, Autism Speaks launched Delivering Scientific Innovation for Autism (DELSIA) in 2012. This nonprofit affiliate will partner with industry to accelerate the translation of genetic and other discoveries into medicines and other treatments that can improve the lives of people with ASD.

At the same time, research published last year expanded our understanding of the role that environmental factors play during prenatal development and early infancy. This is essential for understanding how these factors may interact with genetic susceptibility. These studies looked at factors such as PCBs (polychlorinated biphenyls used in plastic), traffic-related air pollution and maternal infection during pregnancy, among others.18 Environmental research continues to be a high priority for research funding at Autism Speaks.

Progress in Developing More Effective Treatments

Behavioral treatments

The past year likewise brought progress in developing more effective treatments across the lifespan. Evidence continues to accumulate for the effectiveness of early intensive behavioral intervention. Efforts now are focusing on disseminating these interventions to the broader community, including to countries that have limited access to trained professionals. Through Autism Speaks Global Autism Public Health Initiative, we are funding studies that explore the use of web-based technologies for training professionals in remote locations, including rural and underserved American communities. This past year, we helped facilitate the creation of national autism service plans in Albania and Bangladesh. We also helped provide direct training in diagnosis and early intervention in Albania, Bangladesh, China and Saudi Arabia.

Yet another of the year’s research highlights was the finding that early behavioral intervention can produce positive changes in brain activity as well as behavior. This suggests that behavioral interventions not only improve cognitive, language and social skills, they also affect the brain systems that underlie these behaviors.19 TIME Magazine recognized this study as one of its top 10 medical breakthroughs of 2012.

Increasingly, more researchers are focusing on interventions for elementary school and adolescent children. A 2012 randomized controlled trial demonstrated the significant benefits of social skills training for the classmates of children with ASD. This relatively brief intervention had long-lasting benefits in improving children’s relationships with their peers in the classroom and on the playground.20 Another study found that cognitive behavioral social skills training reduced anxiety in children with autism.21 For adults with ASD, mindfulness-based therapy helped reduce symptoms of anxiety and depression.22

Standardizing Medical Treatments

A wide range of medical approaches to treatment for ASD are being explored. In 2012, clinicians in Autism Speaks Autism Treatment Network published the first physician guidelines for the assessment and treatment of medical conditions associated with autism, thanks to funding from Autism Speaks and the federal Health Resources and Services Administration. The guidelines include specific protocols for managing GI problems, sleep and attention difficulties.23

The guidelines draw on studies confirming the usefulness of melatonin for treating insomnia in children with ASD.24 Other studies found that epilepsy, a condition commonly associated with ASD, can disrupt sleep and lead to behavioral disturbances. Research showed that an antiepileptic drug levetiracetam reduces epilepsy-related brain activity during sleep. Another 2012 study found that donepizel helped improve the sleep of children with ASD.25

Also in 2012, a randomized controlled trial of the compound arbaclofen reduced social avoidance in children with fragile X syndrome.26 The same drug, which helps regulate synaptic functioning in the brain, is now being tested in children with ASD without fragile X syndrome. And based on encouraging results from Autism Speaks-funded studies, an NIH-funded multi-site study will assess the effectiveness of the hormone oxytocin for improving social behavior.

Other 2012 health-related research highlighted safety concerns related to the tendency for many children and adults with ASD to wander, or “elope.” This study, co-sponsored by Autism Speaks and other organizations, documented that 49 percent of parents reported that their children often disappear unexpectedly. Many of these children end up in dangerous situations.27 As a result of IACC advocacy, a medical code for wandering/elopement in individuals with developmental disabilities now helps track the prevalence of this significant safety concern.

Another study shed light on the increased mortality associated with ASD. It linked the increased death rate to co-morbid medical conditions such as epilepsy.28 Such knowledge can help focus prevention efforts such as increased monitoring of these health conditions.

Looking ahead – more funding is needed

As I pointed out in an editorial in JAMA Psychiatry this past year, “Although we have witnessed a significant infusion of autism research funding over the past decade, the 78 percent increase in ASD prevalence has been met by an increase of only 43 percent in federal research funding. In other words, the per capita autism federal research funding has deceased from an estimated $62 per person in 2007 to $47.50 per person with ASD today.” Clearly, our efforts advocating for greater investment in autism as a public health priority will be crucial for progress.

I hope my letter provides a glimpse into the steady progress we are making in understanding the causes of ASD and developing more effective methods for prevention and treatment. With more funding, we can greatly accelerate this progress.

I want to close by thanking you for your partnership in this effort through your donations to Autism Speaks. Your support has played a direct role in the majority of discoveries described in this letter – both through the direct funding of studies and through scientific resources such as vital collections of genetic samples and donated postmortem brain tissue.

Your support also makes possible our advocacy efforts, which have produced increased federal research funding and provided direct family support in the form of tool kits and other practical resources developed by Autism Speaks Autism Treatment Network and Family Services. Together, we are making a difference in the lives of people with ASD and their families. I look forward with optimism to 2013.

Warm wishes for a Happy New Year to every person with ASD and their families, friends and community of supporters!

 

 

 

 

Geraldine Dawson

Chief Science Officer

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1. Office of Autism Research Coordination (OARC), National Institute of Mental Health and Thomson Reuters, Inc. on behalf of the Interagency Autism Coordinating Committee (IACC). IACC/OARC Autism Spectrum Disorder Research Publications Analysis Report: The Global Landscape of Autism Research. July 2012. Available at: http://iacc.hhs.gov/publications-analysis/july2012/index.shtml. Accessibility verified January 3, 2013. 

 
2. Regier DA, Narrow WE, Clarke DE, et al. DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses. Am J Psychiatry. Advance online October, 2012.
 
3. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 2012 Mar 30;61(3):1-19.
 
4. Valicenti-McDermott M, Hottinger K, Seijo R, Shulman L. Age at diagnosis of autism spectrum disorders. J Pediatr. 2012; 161: 554-6.  Kočovská E, Biskupstø R, Carina Gillberg I, et al. The rising prevalence of autism: a prospective longitudinal study in the faroe islands. J Autism Dev Disord. 2012; 42: 1959-66. 
 
5. Turner-Brown LM, Baranek GT, Reznick JS, Watson LR, Crais ER. The First Year Inventory: a longitudinal follow-up of 12-month-old to 3-year-old children. Autism. 2012; Aug 2. [Epub ahead of print].
 
6. Bedford R, Elsabbagh M, Gliga T, et al. BASIS team Precursors to social and communication difficulties in infants at-risk for autism: gaze following and attentional engagement. J Autism Dev Disord. 2012; 42: 2208-18.
 
7. Wolff JJ, Gu H, Gerig G, et al; IBIS Network. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry. 2012; 169: 589-600. 
 
8. Elsabbagh M, Mercure E, Hudry K, et al; BASIS Team. Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism. Curr Biol. 2012; 22: 338-42. 
 
9. Shattuck PT, Narendorf SC, Cooper B, Sterzing PR, Wagner M, Taylor JL. Postsecondary education and employment among youth with an autism spectrum disorder. Pediatrics. 2012; 129: 1042-9.
 
10. Cidav, Z., Marcus, SC, Mandell, DS. Implication of childhood autism for parental employment and earnings. Pediatrics. 2012; 129: 617-23.  
 
11. Coe BP, Girirajan S, Eichler EE. The genetic variability and commonality of neurodevelopmental disease. Am J Med Genet C Semin Med Genet. 2012; 160C: 118-29. Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012; 485: 237-41.  
 
12.  Beaudet, AL. Preventable forms of autism? Science. 2012; 338: 342-3. 
 
13. Zoghbi HY, Bear MF. Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harb Perspect Biol. 2012; 4.
 
14. Saxena V, Ramdas S, Ochoa CR, Wallace D, Bhide P, Kohane I. Structural, Genetic, and Functional Signatures of Disordered Neuro-Immunological Development in Autism Spectrum Disorder. PLoS One. 2012, 7:e48835. 
 
15. Glatt SJ, Tsuang MT, Winn M, et al. Blood-based gene expression signatures of infants and toddlers with autism.  J Am Acad Child Adolesc Psychiatry. 2012; 51: 934-44.  
 
16. Breece E, Paciotti B, Nordahl CW, et al. Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors. Brain Behav Immun. 2012; S0889-1591, 00468-0. 
 
17. Silverman JL, Smith DG, Rizzo SJ, et al. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med. 2012; 4: 131ra51.
 
18. Mitchell MM, Woods R, Chi LH, et al. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environ Mol Mutagen. 2012; 53:589-98. Volk H, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic related air pollution, particulate matter, and autism. JAMA Psychiatry. 2012; 1: 1-7.  Atladóttir HÓ, Henriksen TB, Schendel DE, Parner ET. Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics. 2012; 130: e1447-54.
 
19. Dawson G, Jones EJ, Merkle K, et al. Early behavioral intervention is associated with normalized brain activity in young children with autism. J Am Acad Child Adolesc Psychiatry. 2012; 51: 1150-9. 
 
20. Kasari C, Rotheram-Fuller E, Locke J, Gulsrud A. Making the connection: randomized controlled trial of social skills at school for children with autism spectrum disorders. J Child Psychol Psychiatry. 2012; 53: 431-9. 
 
21. Reaven J, Blakeley-Smith A, Culhane-Shelburne K, Hepburn S. Group cognitive behavior therapy for children with high-functioning autism spectrum disorders and anxiety: a randomized trial. J Child Psychol Psychiatry. 2012; 53: 410-9. 
 
22. Spek AA, van Ham NC, Nyklíček I. Mindfulness-based therapy in adults with an autism spectrum disorder: A randomized controlled trial. Res Dev Disabil. 2013; 34(1): 246-53. 
 
23. Perrin, JM, Coury, DL. Improving health care for children and youth with autism and other neurodevelopmental disorders. Pediatrics. 2012; 130 Suppl 2: S57-8.
 
24. Malow B, Adkins KW, McGrew SG, et al. Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes.  J Autism Dev Disord. 2012; 42: 1729-37.
 
25. Larsson PG, Bakke KA, Bjørnæs H, et al. The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study. Epilepsy Behav. 2012; 24: 44-8. 
 
26. Berry-Kravis EM, Hessl D, Rathmell B, et al. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci Transl Med. 2012; 4: 152ra127.
 
27. Anderson C, Law JK, Daniels A, et al. Occurrence and family impact of elopement in children with autism spectrum disorders. Pediatrics. 2012; 130: 870-7.
 
28. Bilder D, Botts EL, Smith KR, et al. Excess Mortality and Causes of Death in Autism Spectrum Disorders: A Follow up of the 1980s Utah/UCLA Autism Epidemiologic Study. J Autism Dev Disord. 2012 Sep 25 [Epub ahead of print].