• What are the early warnings signs?
• Are there typical characteristics that are part of an ASD diagnosis?
• How much variation is there in symptoms and severity associated with ASD?

What do we know?

A child's primary caregivers are often first to identify the signs of ASD. In the classic case, there may be delays or plateaus in a child's attainment of developmental milestones, such as the onset of speech and pretend play. In other cases, the first signs of ASD occur in young children who appear to regress after they seem to have been developing normally. Current diagnostic criteria and classifications of ASD represent progress in identifying a core set of developmental symptoms that, in the past, might have been attributed to other disorders because of more narrowly defined ASD evaluation criteria.

The diagnosis of ASD can be reliably made by age three, because the core symptoms emerge by that time. However, most children eventually diagnosed with ASD exhibit signs of abnormal development well before the age of two. Some children at risk may also begin to experience co-occurring medical symptoms. Recent studies of children at high risk because of a family history of ASD suggest that many cases of autism can be detected by 12 months of age using simple behavioral tests, such as response to calling the child's name or ease of engaging the child in jointly looking at an object (Landa, Holman, & Garrett-Mayer, 2007).

A number of screening tools have been developed for detecting autism for children of varied ages and different levels of clinical severity. A video glossary of early red flags of ASD in young children has been developed to help families and professionals learn how to identify subtle differences in development that may indicate areas of concern (Wetherby et al., 2007). In terms of diagnosis, there is emerging evidence that tools can be developed with sufficiently high sensitivity and specificity to support epidemiologic and risk factor studies.

What do we need?

Most cases of autism and related disorders are not diagnosed until after a child's third birthday, and yet early intervention can have a critical influence on the future course of ASD. At least five issues have limited the use of early interventions. First, it remains difficult to diagnose ASD in very young children because there is considerable healthy variation in the age at which infants and toddlers reach typical developmental milestones (e.g., speech). Delays do not always indicate the presence of a disorder. Pediatricians recognize that most children who are slow to walk or talk will catch up in the second year. Second, diagnosis of an ASD in a person of any age is currently based on behavioral and cognitive signs, reflecting abnormal brain development, but not on detection of brain or other biological differences that may be present before the emergence of the behavioral or cognitive signs. Biomarkers can potentially identify people with ASD, or infants who will subsequently develop or are already developing subtle signs of ASD, so that providers can initiate intensive early intervention strategies to address or possibly preempt developmental delay. Third, children with ASD develop along different trajectories. Some show abnormal behavior soon after birth, others develop normally for the first year or longer and then regress, while others appear to later improve significantly. Greater clarity is needed in identifying these different trajectories and consistency in applying their definitions. Fourth, healthcare and other service providers may not have received training in recognizing the early warning signs of ASD nor use existing screening tools at well check-ups. For example, the American Academy of Pediatrics has recommendations for pediatricians. Fifth, parents and caregivers may be unaware of the early warning signs of ASD, leading to delays in diagnosis.

Although families are eager for guidance, more research is needed to better answer the question of when developmental variation should become cause for concern. We need studies that test both new and current diagnostic and screening methods and that integrate both developmental and biologic approaches in community-based settings. In particular, studies need to be designed to validate methods in underrepresented minorities and disadvantaged populations. Such studies could increase our understanding of barriers to diagnosis and access to services. Taken together, earlier identification coupled with increased access to interventions and services could reduce disparities in health care and service provision, and ultimately improve outcomes for people with ASD.

Scientific studies of ASD require the reliable diagnosis of participants but this can be a time consuming and labor intensive process. Therefore, streamlined diagnostic approaches that facilitate the enrollment of research participants are needed. Researchers also need ASD measures that are easy to administer and are sensitive to changes in clinical status. With regard to heterogeneity, identifying characteristics that are specific to certain ASD subpopulations could potentially identify neurobiological and genetic markers and improve our understanding of more global causal and intervention mechanisms.

Aspirational Goal: Children With or at Risk for ASD will be Identified by 24 Months and Receive Appropriate Interventions

Research Opportunities

• ASD screening instruments and approaches for use in community settings to identify people who require diagnostic evaluation.
• Sensitive and efficient clinical diagnostic tools for diagnosing ASD in widely diverse populations, including underrepresented racial and ethnic groups, females, younger and older age groups.
• ASD measures that are easy to administer and sensitive to incremental changes in both core and associated ASD symptoms. Such measures can be used to help track the clinical course of people with ASD, monitor responses to interventions, and provide information about the broader autism phenotype.
• Detailed criteria for specific ASD sub-types in order to better describe the variations in symptoms and severity and study how these variations relate to underlying pathology, intervention strategies, and outcomes.
• ASD subpopulations and associated biobehavioral markers that provide early indication of ASD risk and opportunities for early intervention.
• Protocols for genetic testing in routine clinical practice in order to identify people at risk for ASD. Identification of people with genetic variations associated with ASD will facilitate intensive studies of ASD subpopulations with shared genetic risk factors to characterize common phenotypic and biological features.
• Inclusion of bioethics considerations into the diagnosis and screening processes, including consideration of the implications of genetic testing.

Short-Term Objectives

• Develop, with existing tools, at least one efficient diagnostic instrument (e.g., briefer, less time intensive) that is valid in diverse populations for use in large-scale studies by 2011. IACC Recommended Budget: $5,300,000 over 2 years.
• Validate and improve the sensitivity and specificity of new or existing screening tools for detecting ASD through studies of the following community populations that are diverse in terms of age, socio-economic status, race, ethnicity and level of functioning by 2012. IACC Recommended Budget: $5,400,000 over 3 years.
  • School aged children
  • General population (vs. clinical population)

Long-Term Objectives

• Identify a panel of biomarkers that separately, or in combination with behavioral measures, accurately identify, before age 2, one or more subtypes of children at risk for developing ASD by 2014. IACC Recommended Budget: $33,300,000 over 5 years.
• Develop at least five measures of behavioral and/or biological heterogeneity in children or adults with ASD, beyond variation in intellectual disability, that clearly relate to etiology and risk, treatment response and/or outcome by 2015. IACC Recommended Budget: $71,100,000 over 5 years.
• Identify and develop measures to assess at least three continuous dimensions of ASD symptoms and severity that can be used by practitioners and/or parents to assess response to intervention for people with ASD across the lifespan by 2016. IACC Recommended Budget: $18,500,000 over 5 years.