• What is happening early in development?
• Are there known biological differences that help explain ASD symptoms?
• Are there subgroups of people with ASD that have been identified?

What do we know?

Researchers, clinicians, and families have long posed questions about the possible biological bases of ASD. Clinicians classify ASD as a developmental brain disorder based on the behavioral features required for diagnosis. Little evidence exists, however, for a specific neurological abnormality beyond reports of an exuberant and transient pattern of brain or head growth (Akshoomoff, Pierce, & Courchesne, 2002; Dawson et al., 2007; Hazlett et al., 2005). While many scientists believe that the behavioral features of ASD result from atypical brain wiring or connections in synapses, they have not reached a consensus on a specific neural variance associated with ASD. Nevertheless, there are some promising leads, and projects are underway that have the potential to provide biological signatures of some forms of ASD.

The development of sophisticated magnetic resonance imaging (MRI) methods has enabled researchers to accurately visualize many aspects of brain structure and functioning. For example, many children and adults with ASD perceive and analyze the visual information conveyed by facial expression differently than do other people (Spezio et al., 2007). Other researchers have employed MRI methods to investigate differences in brain anatomy between people with and without ASD, and have found differences in the density of white and gray matter, in some cases linked to specific symptoms of ASD (Craig et al., 2007).

Frequently, people with ASD experience co-occurring behavioral and medical symptoms. In the case of the immune system, a number of hypotheses concerning how disruptions might contribute to ASD and other neurodevelopmental disorders have emerged in recent years. Some recent findings suggest that the immune systems of parents and their children may affect early brain development and the onset and fluctuation of symptoms in some children with ASD (Pardo, Vargas, & Zimmerman, 2005). For example, research on the effect of maternal antibodies, proteins produced as part of the immune response, on an array of fetal brain proteins suggested that in some cases maternal antibodies could interfere with normal brain development (Braunschweig et al., 2008). These questions have been receiving increasing attention in recent years but it is too early for clear answers. While such medical symptoms may not be entirely specific to ASD, treating them may have significant impact on quality of life, symptom severity, and level of functioning.

Exploring the neural basis of ASD requires access to biospecimens of people with and without ASD. Some progress has been made to establish the necessary infrastructure for the collection and preservation of post-mortem tissue from people with ASD. Nevertheless, the tissues currently available are insufficient for the needs of researchers. Educational campaigns, through contact with healthcare providers and the internet, may be useful to increase public awareness.

What do we need?

One of the greatest barriers to progress in determining the biological bases of ASD has been the heterogeneity of the spectrum. A clear need exists to advance understanding of the many phenotypes of ASD, including studies that link genotype to phenotype, investigations of natural and treated history, analyses of genetic interaction with environmental exposures, and studies of co-occurring medical conditions.

To determine the earliest discernable onset of ASD, experts have expressed the need for an intensive, multidisciplinary study starting at early ages that examines biomedical, neurodevelopmental, and behavioral trajectories of children with ASD. A parallel multidisciplinary analysis of typically developing children would be especially enlightening, as limited normative information is currently available. An evaluation of differences in environmental exposures between children with and without ASD is also needed. Understanding early trajectories may lead to targeted interventions aimed at mitigating behavioral and medical challenges and improving outcomes through adulthood.

Another understudied arena of ASD research is gender differences. Many studies of autism preferentially enroll males, which, due to a 4:1 increased prevalence, are easier to recruit. Without additional information about the biological features of ASD in females, it remains unclear whether the course of ASD is similar and whether currently used interventions are appropriate for females. It is critical to determine whether the gender ratio is accurate and whether gender is related to protective factors, diagnosis, and trajectory.

Many in the field have highlighted the need to establish nationally coordinated strategies for the collection and preservation of post-mortem tissue from both people with and without ASD. The existing brain and tissue bank resources cannot satisfy the high demand and the continuously increasing demand for post-mortem tissue by scientific investigators. Currently, the numbers of well-preserved brains, and the specimens include a number of varying co-occurring conditions and are of limited developmental range. Furthermore, there are few matched controls available for the resources in the existing repositories.

Aspirational Goal: Discover How ASD Affects Development Which Will Lead to Targeted and Personalized Interventions

Research Opportunities

• Multi-disciplinary, longitudinal, biobehavioral studies of children, youths, and adults beginning during infancy that characterize neurodevelopmental and medical developmental trajectories across the multiple axes of ASD phenotype and identify ASD risk factors, subgroups, co-occurring symptoms, and potential biological targets for intervention. Such studies could include:
  • High-risk siblings of children, youths, and adults with ASD, children without a family history of ASD, and typically developing children.
  • Multi-disciplinary assessments of brain imaging, metabolic and immune markers, microbiomics, electrophysiology, and behavior.
• Research on females with ASD to better characterize clinical, biological and protective features.
• Human and animal studies that examine immune, infectious and environmental factors in the occurrence of ASD.
• An international public-private collaboration to expand current postmortem brain and other tissue resources (e.g., skin fibroblasts) to increase the acquisition, quality, type and availability of biomaterials relevant to studying the pathology of ASD.
• Research on the unique strengths and abilities of people with ASD.

Short-Term Objectives

• Establish an international network of biobanks for the collection of brain and other tissue (e.g., skin fibroblasts) with acquisition sites that use standardized protocols for phenotyping, collection and distribution of tissue by 2011. IACC Recommended Budget: $10,500,000 over 2 years.
• Support at least four research projects to identify mechanisms of metabolic and/or immune system interactions with the central nervous system that may underlie the development of ASD during prenatal-postnatal life by 2010. IACC Recommended Budget: $9,800,000 over 4 years.
• Launch three studies that specifically focus on the neurodevelopment of females with ASD by 2011. IACC Recommended Budget: $8,900,000 over 5 years.
• Identify ways to increase awareness among the autism spectrum community of the potential value of brain and tissue donation to further basic research. IACC Recommended Budget: $1,400,000 over 2 years.

Long-Term Objectives

• Complete a large-scale, multi-disciplinary, collaborative project that longitudinally and comprehensively examines how the biological, clinical, and developmental profiles of children, 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.
• Maintain an international network of biobanks and support continued collection of brain and other tissue. IACC Recommended Budget: $22,200,000 over 5 years.