Disruption in the number and function of brain synapses — the connections between neurons — is a central feature in the development of autism and associated cognitive disabilities. Although our understanding of how brain development differs in autism is not complete, an early overgrowth of neurons and synapses, as well as a failure to prune inappropriate synapses, has been observed in the brains of children with autism and in autism mouse models. At the molecular level, overproduction of key synaptic proteins may contribute to the atypical neural and synaptic growth in autism.

Rett syndrome involves a number of developmental deficits similar to those observed in autism, including dysregulated motor movements, communication skills and cognitive processes. Rett syndrome is caused by mutations in a single gene, MeCP2, allowing researchers to study the disorder in mice that carry the mutations.

Autism is a deeply complex and poorly understood developmental brain disorder. Defined genetic disorders that cause autism may be instructive for unraveling the cellular and developmental changes that underlie the disorder.

Significant progress has been made in recent years in identifying genetic factors contributing to autism. Although the genes identified have diverse biological functions, many of them are important for controlling the structure and function of the connection points between brain cells, called synapses. Alterations in synapse function affect the ability of brain cells to communicate with each other, and can lead to imbalanced or inappropriate activity in brain networks.

The core set of behavioral symptoms that define autism spectrum disorders can arise from a wide array of genetic and environmental causes. This many-to-one correspondence between genetic causes and behavioral phenotypes suggests that understanding and eventually treating autism may depend on identifying common intermediate biomarkers  at the level of neural circuits or biochemical pathways.

People with autism spectrum disorders have more mutations in their DNA than do their unaffected siblings. The emerging picture is that the genetics of autism is very complex: Dozens or perhaps even hundreds of different mutations may contribute to the disease in each person with autism.

A hallmark symptom of autism spectrum disorders is impairment in social interactions, yet little is known about the neural mechanisms underlying this deficit. In contrast to autism, Williams-Beuren syndrome involves enhanced sociability. The syndrome affects many systems, including the motor, sensory, language, cognitive, emotional and social systems. It is caused by a chromosomal microdeletion. Most individuals with the disorder have relatively preserved language skills in conjunction with high sociability, which are quite opposite from the salient features of autism.

Choline is an essential nutrient for all animals, including humans. Prenatal and early postnatal supplementation with choline has been shown to enhance long-term cognitive performance, improve motor deficits in a mouse model of Rett syndrome, and reduce the adverse effects of neonatal alcohol exposure in rodents.

In recent years, autism heritability has been the focus of intense research, and a number of autism susceptibility genes and loci have been identified. This progress has allowed researchers to generate mouse models that carry relevant mutations, providing a biological system for dissecting the circuit, cellular and molecular mechanisms underlying autism-associated changes in brain development.