Autism spectrum disorders (ASDs) are genetically heterogeneous, but whether they share a common neural-circuit-processing defect is unclear. One hypothesis is that the ratio of excitation to inhibition (the E/I ratio) in the brain's cerebral cortex is elevated in ASDs. Elevations in this ratio could cause hyperexcitability of neural circuits, leading to impaired information processing and hypersensitivity to sensory stimuli, features commonly seen in individuals with ASD.

Animal models play pivotal roles in understanding the relationship between behaviors and underlying brain circuits. One of the key features of autism is a deficit in social communication, including vocal communication. The primary animal models for autism research have been rodents because of the advantage of genetic manipulations. However, rodents lack certain social communication behaviors exhibited by primates, such as eye contact and high-level vocal communication. There is therefore a great need to develop new animal models, preferably nonhuman primate models, for autism research.

A core feature of autism is the expression of repetitive and ritualized behaviors characterized by profound invariability and inflexibility. Autism is also frequently comorbid with anxiety disorders. Despite intensive study, the mechanisms underlying the repetitive and ritualized behavior in autism and the high prevalence of comorbidity between autism and anxiety disorders remain largely unknown.

Dysregulation of the normal immune response appears to underlie the development of a wide variety of neurodegenerative diseases, including autism spectrum disorders (ASDs). Animal models of ASD have demonstrated that maternal infection or abnormal immune signaling contribute to the development of autism-like disorders. Together, these findings suggest that immune response genes play an important role in the generation of ASDs.

All cells, including neurons, possess mechanisms to coordinate protein synthesis with protein degradation to maintain amino acid and protein levels within the appropriate range. Even a subtle imbalance between these processes can disrupt normal neuronal morphology and functions.

The sense of touch allows us to navigate our physical world. The first step in tactile processing involves the activation of low-threshold mechanoreceptor neurons (LTMRs) with highly specialized endings in the skin. Social (affective) touch may be mediated by a unique class of slowly conducting C-fibers, the C-LTMRs.

The cause of autism is thought to involve a combination of both genetic and environmental factors. One approach to understanding the genetic contribution to autism has been to use large samples to investigate multiple genes associated with the disorder. This approach, known as a genome-wide association study, has resulted in several interesting genetic ‘hits,’ — the discovery of genes that appear to be associated with autism.

The proposed research takes advantage of the resources available at the University of Oxford in the U.K. to validate a new noninvasive magnetic resonance imaging (MRI) biomarker of autism using postmortem imaging. This has enormous potential for subsequent development as a tool for early detection, diagnosis, monitoring and assessment of individuals with autism. Steven Chance and his colleagues seek to better understand the cause of autism by investigating the neuroanatomical basis of the condition. Accurate diagnosis in life is difficult because the detailed changes in the cerebral cortex cannot be seen in brain imaging of living people.

Autism is diagnosed in boys four times more frequently than in girls. Recent genetic research suggests that this difference is due to the fact that girls are protected from autism risk factors rather than boys being subjected to additional risk factors. The nature of this ‘female protective effect’ remains unknown.

Anatomic and molecular features observed in the brains of individuals with autism suggest that abnormalities in early embryonic development underlie the development of autism. Mutations in a gene called CHD8 are the most commonly identified mutations associated with autism. How CHD8 influences the disorder remains unknown, but observations that children with autism and CHD8 mutations have abnormally large heads (macrocephaly) support the possibility that CHD8 functions in regulating brain growth during development.