Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research – 2013 UpdateSkip Over Navigation Links
- Question 1: When Should I Be Concerned?
- Question 2: How Can I Understand What Is Happening?
- Question 3: What Caused This to Happen and Can It Be Prevented?
- Question 4: Which Treatments and Interventions Will Help?
- Question 5: Where Can I Turn for Services?
- Question 6: What Does the Future Hold, Particularly for Adults?
- Question 7: What Other Infrastructure and Surveillance Needs Must Be Met?
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Question 2: How Can I Understand What Is Happening?
Aspirational Goal: Discover how ASD affects development, which will lead to targeted and personalized interventions.
Over the course of the last several years, a great deal has been learned about altered neurodevelopment in ASD and a few interventions are in the early phases of testing. The knowledge base, however, is still not sufficient to support the long-term goal of personalized interventions. Objectives within Question 2 have also evolved as the science has provided more insight into the complexity of ASD. Specifically, through recent groundbreaking brain mapping and brain imaging research, much has been learned about how the brain develops and how autism unfolds in early development. Insights from syndromic forms of ASD (ASD that is caused by known genetic syndromes) have provided clues about the general mechanisms and genetic pathways that are affected in ASD. Recent studies have also begun to elucidate the role of the immune system in brain development and potentially in autism, and progress has been made in understanding and developing guidelines to address co-occurring conditions such as gastrointestinal (GI) symptoms, sleep disorders, and epilepsy that can greatly impact quality of life for people with ASD. Finally, the biological mechanisms by which specific gene mutations cause syndromic autism are now better understood.
Progress Toward the Strategic Plan Objectives
The 2009 IACC Strategic Plan, which was revised in 2010 and 2011, included nine objectives under the heading of Question 2, encompassing seven short-term objectives and two long-term objectives designed to address gaps in current research on the biological basis of autism. IACC Portfolio Analysis data from 2008-2012 indicated that the cumulative investment in research categorized under Question 2 during this period was $362 million. Approximately half of the investments that align with Question 2 were made in gap areas identified in the IACC Strategic Plan objectives, while the other half were invested in core/other research activities on the underlying biology of autism. The substantial activity in core/other research areas indicates long-standing investment in research toward understanding the biology of autism that has been augmented by growth in emerging areas of scientific research.
Of the nine objectives in Question 2, four objectives (addressing fever and immune system interactions with the central nervous system (CNS), biological pathways of genetic conditions related to autism, biological mechanisms of co-occurring conditions, and specific genotypes that underlie ASD phenotypes) met or exceeded the recommended budget and fulfilled the recommended number of projects. The remaining five objectives (studies on females with ASD, raising awareness of brain and tissue donation, characterization of regression, application of biosignatures to diagnosis, and large scale longitudinal studies of diverse populations with ASD) were below the recommended budget and number of projects. However, some progress has been made on all objectives.
Of note, in 2009, NIH received funds from the American Recovery and Reinvestment Act (ARRA) that were used to support a series of initiatives totaling $122 million over 2 years on key scientific areas. The heterogeneity of ASD was one such area, encompassing research on topics that were responsive to the newly released IACC Strategic Plan for ASD Research, such as basic biology of ASD, biomarkers, risk factors, and treatments. This infusion of new funds helped jumpstart efforts to address IACC Strategic Plan objectives and is reflected in the portfolio across all Questions of the IACC Strategic Plan.
Progress in Longitudinal and Comprehensive Examination of the Biological, Clinical, and Developmental Profiles of Individuals with ASD
Autism is considered a neurodevelopmental disorder that begins in early life, and longitudinal studies are necessary to understand how brain function is altered throughout the lifespan. Indeed, much science points to the prenatal period and the first years of life as the critical window for onset and development of ASD. Recent gene expression studies demonstrated that key ASD-related genes and genetic pathways are activated during specific times in fetal development.1, 2 Furthermore, epidemiological studies have found that prenatal conditions and environmental exposures, such as air pollution and certain medication use, are associated with increased risk, while prenatal vitamin use appears to reduce risk.3–8 A recent small, longitudinal study of infants demonstrated normal eye tracking behavior that then declined over 2-6 months after birth predicted later development of autism.9 Another study found that white matter tracts in infants who develop ASD are detectably different from those of neurotypical children at 6-24 months of age.10 Additionally, a number of imaging studies have demonstrated greater brain volume in ASD, but only during a specific early developmental stage.11 Other functional and structural imaging studies are beginning to uncover correlates of ASD differences in processing of visual12 and language13 inputs. New sophisticated techniques to look at brain structure and function such as resting state magnetic resonance imaging (MRI), resting state electroencephalography (EEG), magnetoencephalography (MEG), and magnetic resonance spectroscopy (MRS) are being used to noninvasively examine neural circuits in ASD. Repeated over time, these measures can help chart neurodevelopment. Such techniques hold the potential to be useful for early diagnosis as well as measure efficacy of therapies that harness neuroplasticity to improve functional deficits.
Progress in the Fields of Fever, Metabolism, and Immunity
Research on the potential relationship between the immune system and ASD has grown considerably over the past 2 years, resulting in several major breakthroughs. In the realm of basic developmental research, immune cells and immune signaling molecules have been identified as essential for establishing stable connections between neurons during early brain development.14, 15 Brain tissue studies of the expression patterns of genes have indicated differences in immune pathways in those with autism compared to that of typically developed individuals.16, 17 Of note, the role of immune genes was not detected in population genetic studies, suggesting a non-genetic basis for the immune differences.1, 2 Specific autoantibodies targeting fetal brain proteins have been found in a subgroup of mothers of children with ASD and in some children with ASD.18 These maternal autoantibodies appear to alter neurodevelopment in non-human primates.19 Further, children born to mothers with these autoantibodies were found to have an abnormal brain enlargement in MRI studies compared to that of typically developing controls and persons with ASD without the antibodies.20 Preliminary research findings suggest that metabolic and immune factors may play a role in ASD in some individuals.21–26 Reports of improved behavior in persons with ASD during periods of fever still remain unexplained, warranting further efforts in this area.27
In addition, there have been intriguing new findings with regard to the role of metabolism in autism. For example, a rare hereditary form of autism that presents with epilepsy and intellectual disability is caused by mutation of a gene that codes for the enzyme BCKDK (Branched chain ketoacid dehydrogenase kinase), which prevents the body from breaking down the essential branched-chain amino acids leucine, isoleucine, and valine after eating food.25 When BCKDK is inactivated, individuals cannot maintain adequate levels of the above mentioned amino acids and they experience a deficiency. The problem can be addressed through amino acid supplementation, but research is needed to determine whether supplementation can reverse the autism symptoms associated with this disorder in humans. In a separate study, preliminary findings have linked a rare form of autism with a gene defect that interferes with the body's ability to manufacture carnitine, an amino acid that helps convert fat into energy, suggesting that another form of autism also may be potentially amenable to treatment through nutritional supplements.26 Further work in this emerging field may yield new insights into the mechanisms of ASD and potential for novel treatments.
Progress in Understanding Neurodevelopment in Females
While ASD affects more males than females, there is a growing awareness that ASD in females may be underdiagnosed, potentially due to differences in the manifestations of ASD in females, such as less disruptive behavioral disorders and stronger ability to recognize emotions in facial expressions, which mask symptoms.28, 29 Multiple familial and genetic studies suggest that female gender may protect against autistic behavior and that more genetic disruptions are required to cause autism in females.30, 31 The abnormal brain growth patterns that have been observed in people with ASD are also more pronounced in females than in males.11, 32, 33 One of the newly funded NIH Autism Centers of Excellence (ACE) networks, including Yale University, the University of California Los Angeles, Harvard, and the University of Washington, is now devoted to understanding this potential "female protective factor".34
Progress in the Field of Brain and Tissue Donation
The research community is in extreme need of brain and other types of tissue to enable important studies. One example of the value of brain tissue is the recent study using modern stereological techniques. In this study, researchers observed that young children with autism have 67 percent more neurons in the prefrontal cortex – the region of the brain centrally involved in higher-order social and communication behaviors.35 Since prefrontal neurons are generated in the second trimester, this neuron excess indicates that abnormal brain development in autism begins before birth. These types of studies can only be performed if appropriate brain tissue is available. The Autism BrainNet initiative, a multi-site, private effort supported by the Autism Science Foundation, the Simons Foundation, Autism Speaks, and the Nancy Lurie Marks Family Foundation, will target autism specifically and will include an autism-specific brain donation outreach campaign to address this need. In the public sector, NIH recently launched the NIH Neurobiobank which includes samples for research on autism as well as other brain disorders and has an associated online publication "Why Brain Donation? A Legacy of Hope" (PDF - 946 KB) to increase awareness about brain donation. As efforts to collect brain tissue progress, the collection of other biological samples from very young children at risk for ASD is another potential opportunity to facilitate multidisciplinary efforts to establish biomarkers of ASD risk.
Progress in Understanding Genetic Conditions Related to Autism and Synaptic Function
The largest area of scientific progress related to Question 2 has come from studies of the biological processes regulated by genes that either cause syndromic forms of autism (Fragile X syndrome, Rett syndrome, Tuberous Sclerosis) or are associated with increased risk of non-syndromic autism. Overlap has been uncovered in the biological mechanisms that give rise to ASD, especially at the level of synaptic function. For instance, deletion or mutation of the SHANK3 gene is known to cause one type of syndromic autism,36 and the Shank3 protein encoded by this gene was found to play a critical role in the function of glutamatergic synapses – those synapses that transmit neuronal signals using the excitatory neurotransmitter glutamate.37 Glutamatergic neurotransmission was also found to be altered in Fragile X and Tuberous Sclerosis, two other syndromes that often include autism.38, 39 A variety of other rare genetic mutations associated with autism have been found to affect synaptic function, raising the question of whether a common synaptic deficit with multiple causes results in autism. After finding these functional deficits at the synapse, investigators have asked whether it is possible to reverse functional synaptic deficits and indeed this has been demonstrated in some animal models.40 Moreover, early stage clinical trials have been mounted to treat Tuberous Sclerosis with rapamycin, a drug that affects synaptic transmission via effects on mTOR signaling,41 and non-syndromic autism with specific synaptic glutamate receptor antagonists.42 Recent studies have shown that oxytocin can alter synaptic function and that the oxytocin receptor gene may be mutated or epigenetically altered in people with ASD.43–45 Consistent with these findings, exciting new clinical trial data suggest that intranasal oxytocin can improve social function in ASD.46, 47
The new field of epigenetics, the study of DNA modifications (such as methylation – the addition of methyl chemical groups onto DNA, causing the "silencing" of genes) that change over time and affect gene expression, have also been explored in ASD-related research. Recent publications have found that the methylation of DNA occurs in several brain regions in autism.48 One report determined that the DNA in typically developing females is less methylated than that of females with ASD. A similar trend is observed in neurotypical males compared to males with ASD.49 Furthermore, new data suggests that there are various genetic alterations and mutations in neurons that may occur during development.50 Evidence suggesting that DNA hypermethylation may be involved in the development of cerebellar abnormalities associated with ASD has also emerged, thus reinforcing the value of integrative genomic approaches in better understanding the etiology of ASD.51
Progress in Understanding Conditions Co-occurring with Autism
Much progress has been made in understanding the prevalence and biology of conditions that commonly co-occur with ASD, including epilepsy, sleep disorders, gastrointestinal (GI) disturbances, attention deficit hyperactivity disorder, and other psychiatric comorbidities.52–57 A recent study found three distinct patterns of specific co-occurring conditions in persons with ASD, which suggests that such groupings of symptoms may represent distinct etiologies with different genetic and environmental contributions.58 In 2012, an NIH workshop on epilepsy and ASD offered recommendations for next steps and research opportunities to better understand seizure disorders in ASD.59 The workshop report reviewed several studies that identified genetic mutations, malfunctioning ion channels, interneuron deficits, and other factors that may play a critical role in ASD with co-occurring seizure disorders. In the field of sleep, abnormalities in circadian rhythms have been identified as potential cause of sleep disorders in ASD.60 Outside the central nervous system, several recent studies have pointed to differences in gut microbiota as playing a potential role in ASD.61–63 In a recent finding, the common co-occurring issue of gastrointestinal (GI) dysfunction was linked to ASD and treatment with a probiotic ameliorated the bacterial, GI, and behavioral changes in a mouse model,62 suggesting the possibility of probiotic treatments to help a subset of individuals whose ASD is accompanied by GI symptoms. Another common issue reported by families with a member on the autism spectrum in a recent research study is the propensity for children with ASD to wander away from safe environments.64 Currently, though wandering/elopement presents an important safety issue for families with children on the spectrum, there is very limited knowledge regarding the biological basis of this behavior and further research is needed in this area.
Progress Toward the Aspirational Goal
The challenges to understanding the underlying mechanisms of ASD are substantial. One opportunity for expanding the research horizon in ASD is to understand the gender-associated protective factors in females, as this might lead to therapeutic breakthroughs. The roles of the immune system in sculpting neural circuits and in neuroinflammation's response to stress also need further elucidation. It is especially important to be able to gauge the effects of maternal immune processes on the developing fetal brain. Careful longitudinal studies of important neurodevelopmental processes are needed as studies examining single time points are likely to miss important occurrences in this dynamic period of brain development. There is still very little known about why certain children with autism are noted to deteriorate over relatively short periods of time. Ongoing longitudinal studies of high risk children may lead to a better understanding of regression and whether it is a distinct syndrome or part of the continuum of neurodevelopmental abnormalities in ASD. The underlying basis for various disabilities (e.g., verbal vs. non-verbal ASD), specific behaviors, heterogeneity in severity, sleep disorders, and gastrointestinal disturbances remain poorly understood and lack effective treatments. A systems biology approach is thus necessary to understand the multifaceted disturbances that occur in ASD.
Many new tools to further reveal the biological basis of ASD are emerging. Launched in 2013, the President's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, which aims to map the interactions of individual brain cells and complex neural circuits, is focused on neurotechnology development. It will advance the ability to characterize the cellular differences in ASD compared to typically developing individuals. It also promises to substantially improve the ability to record brain circuit activity that would be helpful to monitor neurodevelopment or to guide therapy in ASD. One such tool that will promote advances relevant to the BRAIN initiative is Clear, Lipid-exchanged, Anatomically Rigid, Imaging/immunostaining compatible, Tissue hYdrogel (CLARITY), a new technology that aids in the visualization of human brain structure as well as the localization of proteins, neurotransmitters, and gene expression patterns. This neurotechnology is already being used to study the brain of a person affected by autism.65 Induced pluripotent stem cell (iPSC) technology is another revolutionary tool, which enables scientists to transform cells (drawn from simple skin biopsies) into nerve cells.66, 67 Such methods can be used to research biological phenotypes observed in autism (i.e., synaptic dysfunction),37, 68, 69 examine specific genes and pathways that are differentially regulated, and screen drugs for their ability to ameliorate autistic phenotypes.70 Breakthroughs in RNA sequencing (a technique that reveals which genes are being expressed) and epigenetics now allow powerful new studies of gene regulation in brain tissue. In the world of imaging, the NIH's Human Connectome Project aims to produce a detailed map of brain connections in those with ASD and to visualize how this map changes over time from infancy through childhood. These and other techniques bring together tremendously large amounts of data from a variety of tissues and cells to enable systems biology approaches to understand the connections between different systems, including genetics, brain circuits, the immune system, metabolism, and the microbiome. The richness of the data and the variety of tools needed call for a coordinated approach in which findings are replicated and the tools validated so that they can become clinically useful.
Question 2 Cumulative Funding Table
|IACC Strategic Plan Objectives||2008||2009||2010||2011||2012||Total|
|Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010 (Fever studies to be started by 2012).
IACC Recommended Budget: $9,800,000 over 4 years
|2.S.A. Funding: The recommended budget for this objective was met.
Progress: Many projects were funded in this area (approximately 20-30 per year), but the field is still developing, and emphasis on this objective should continue in the future. Scientific advances have been made in linking maternal innate immune function and immune-system challenge to aspects of ASD. Methodological advances in the field include the development of animal models for study of the role of the immune system in ASD and PET ligands for imaging microglial activation.
Remaining Gaps, Needs and Opportunities: There is a need for a well-designed, multi-site clinical study of clinical effects of fever and to develop standard measures of fever and behavioral/cognitive outcomes. Questions about fever could be integrated into funded epidemiological studies. There is also interest in further work on metabolic and mitochondrial issues, but in order for this work to be done, there is a need for validation and standardization of measures for assessment of oxidative stress and mitochondrial function. More guidance is needed on the key questions for this field to answer – a workshop to define these methodologies may be helpful. One of the key questions is to determine whether it is the body temperature associated with fever or some consequence of immune activation and production of the febrile state that leads to amelioration of cognitive function.
|Launch three studies that specifically focus on the neurodevelopment of females with ASD, spanning basic to clinical research on sex differences by 2011.
IACC Recommended Budget: $8,900,000 over 5 years
|2.S.B. Funding: The recommended budget was partially met.
Progress: More than the minimum three studies recommended were launched, but further work is needed in this area. Studies have found that females with ASD often have a higher burden of ASD genetic risk mutations than males, suggesting a gender-associated protective effect in females. Research on factors protecting females from developing ASD symptoms even when challenged with genetic mutations that lead to ASD in boys may help to identify approaches to prevent development of ASD symptoms in both genders.
Remaining Gaps, Needs and Opportunities: Studies of protective and compensatory effects in females and differential response to treatment based on gender are promising areas that could help with future prevention and effective, personalized treatment efforts. Beyond genetic differences, it is important to determine whether other biological features, such as differences in neuropathology, are found in the two sexes.
|Identify ways to increase awareness among the autism spectrum community of the potential value of brain and tissue donation to further basic research by 2011.
IACC Recommended Budget: $1,400,000 over 2 years
|2.S.C. Funding: The recommended budget was partially met.
Progress: Loss of autism brain samples due to a freezer malfunction at a major brain bank in 2012 has caused a loss of progress in ASD research. Thus, there is a need for new samples to replace those that were lost and to begin expanding the amount of brain tissue available for ASD research. The Autism BrainNet initiative is a multi-site, privately funded effort that will target autism specifically and will include an autism-specific brain donation outreach campaign that addresses this objective. NIH launched the NIH Neurobiobank ($5 million), which includes samples for research on autism as well as other brain disorders, and has an associated online publication "Why Brain Donation? A Legacy of Hope" to increase awareness about brain donation. Both of these initiatives are not yet reflected in the Portfolio Analysis, because they began in 2013. In addition to these new brain banking efforts, the NICHD Brain and Tissue Bank produced a video for their website to generally increase awareness the potential value of brain and tissue donation to further basic research on neurodevelopmental and pediatric conditions. Since the effort is not autism-specific, it was not captured in the portfolio analysis.
Remaining Gaps, Needs and Opportunities: There is an ongoing and urgent need to raise awareness of the importance of brain and tissue donation for research, to standardize the methodology of collection and to increase the supply of such tissues. Autism BrainNet, a private outreach and postmortem brain donation program dedicated to research on autism and related disorders will integrate the Autism Tissue Program (ATP) with collection sites at Mount Sinai School of Medicine, the University of Texas Southwestern Medical School, and the University of California, Davis MIND Institute.
|Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g., Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012.
IACC Recommended Budget: $9,000,000 over 5 years
|2.S.D. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.
Progress: A large number of projects were funded that address this objective. Investment in this area has doubled since 2009, and in 2013, NIH began funding an ACE center focused on tuberous sclerosis. Much is being learned about conditions related to autism that can be applied to autism. This objective is on track.
Remaining Gaps, Needs and Opportunities: The next step will be to translate findings in this area into clinically useful therapies.
|Launch three studies that target the underlying biological mechanisms of co-occurring conditions with autism, including seizures/epilepsy, sleep disorders, wandering/elopement behavior, and familial autoimmune disorders, by 2012.
IACC Recommended Budget: $9,000,000 over 5 years
|2.S.E. Funding: The recommended budget for this objective was met.
Progress: More than twenty projects were funded that were specific to this objective. Scientific advances in this area include mechanistic and mutation linkages of epilepsy and ASD-like behaviors, as well as circadian rhythm disruptions downstream of ASD-associated mutations.
Remaining Gaps, Needs and Opportunities: While studies on co-occurring conditions have been initiated, a greater depth of understanding is needed. Further efforts are needed, especially on wandering, metabolic and immune conditions related to ASD, as well as a systems-biology approach to understand how these co-occurring conditions are related to ASD. In order to more accurately assess progress, wandering/elopement should be considered separately from seizures/epilepsy/sleep. Familial autoimmune disorders could be moved to 2.S.A to be grouped with other immune-related issues.
|Launch two studies that focus on prospective characterization of children with reported regression to investigate potential risk factors by 2012.
IACC Recommended Budget: $4,500,000 over 5 years
|2.S.F. Funding: The recommended budget was partially met.
Progress: The number of recommended projects has been met and progress is being made, but further work is needed to understand how autism develops. Some recent data suggest that regression may be more of a continuum than a distinct type of autism, and several studies have provided new descriptions of ASD developmental trajectories. However, other studies have found some differences between children with reported regression vs. children without reported regression.
Remaining Gaps, Needs and Opportunities: Further work is needed to better understand subtypes and potential biomarkers. High-risk siblings may present an opportunity for studying regression prospectively.
|Support five studies that associate specific genotypes with functional or structural phenotypes, including behavioral and medical phenotypes (e.g., nonverbal individuals with ASD and those with cognitive impairments) by 2015.
IACC Recommended Budget: $22,600,000 over 5 years
|2.S.G. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.
Progress: Over 40 projects have been funded in this area, and the projects cover the areas described, so the objective appears to be on track.
Remaining Gaps, Needs and Opportunities: With so many studies initiated, the next step is to encourage multi-site collaboration in order to achieve the large number of subjects required for meaningful data interpretation.
|Complete a large-scale, multidisciplinary, collaborative project that longitudinally and comprehensively examines how the biological, clinical, and developmental profiles of individuals, with a special emphasis on females, youths, and adults with ASD, change over time as compared to typically developing people by 2020.
IACC Recommended Budget: $126,200,000 over 12 years
|2.L.A. Funding: The recommended budget was partially met.
Progress: Several projects have been funded in this area, and the ACE Network continues to collect data relevant to this objective.
Remaining Gaps, Needs and Opportunities: Though this research is underway, more clinical studies are needed over a longer trajectory to identify issues faced as people with ASD age, especially with regard to risk factors for other medical conditions. Another remaining need is that of standardization of data collection and analysis methods.
|Launch at least three studies that evaluate the applicability of ASD phenotype and/or biological signature findings for performing diagnosis, risk assessment, or clinical intervention by 2015.
IACC Recommended Budget: $7,200,000 over 5 years
|2.L.B. Funding: The recommended budget was partially met.
Progress: Imaging studies have developed activity signatures of the ASD brain. While more than 3 studies were launched, more funding and work in this area are needed.
Remaining Gaps, Needs and Opportunities: This objective also requires standardization of data collection and analysis methods, as well as collaboration among investigators to pool data. Increased emphasis must be placed on conducting biological evaluations of very young children at risk for ASD and on collecting biological samples from these young children, to enable research into the establishment of biomarkers or risk markers in this population.
|Not specific to any objective (Core/Other Activities)||2.Core/Other Activities
|Total funding for Question 2†||$40,621,403
Table 2: Question 2 Cumulative Funding Table, see appendix for a color-coding key and further detail.
* This total reflects all funding for projects aligned to current objectives in the 2011 IACC Strategic Plan and incorporates funding for projects that may have been coded differently in previous versions of the Plan.
† The totals reflect the funding and projects coded to this Question of the Strategic Plan in the particular year indicated at the top of the column. When reading each column vertically, please note that the projects and funding associated with each objective for the years 2008, 2009, and 2010 may not add up to the total at the bottom of the column; this is due to revisions of the Strategic Plan that caused some objectives to be shifted to other Questions under the Plan. The projects and funding associated with these reclassified objectives are now reflected under the Question in which they appear in the 2011 Strategic Plan.
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NIH Medical Arts
All material appearing in this report is in the public domain and may be reproduced or copied. A suggested citation follows.
Interagency Autism Coordinating Committee (IACC). IACC Strategic Plan for Autism Spectrum Disorder (ASD) Research —2013 Update. April 2014. Retrieved from the U.S. Department of Health and Human Services Interagency Autism Coordinating Committee website: http://iacc.hhs.gov/strategic-plan/2013/index.shtml.