The underlying causes of autism spectrum disorders are poorly understood, but one appealing hypothesis is that an imbalance of excitation and inhibition in the brain’s cortex underlies a significant proportion of autism cases.

A number of the genes that have been implicated in autism have counterparts in model organisms, such as mice and fruit flies. This evolutionary conservation allows researchers to gain insights into the molecular pathways in which these autism-linked genes function. Lawrence Zipursky, of the University of California, Los Angeles, and his colleagues are studying one such conserved gene and its role in brain development.

Flora Vaccarino and her colleagues at Yale University have developed and characterized several lines of human induced pluripotent stem (iPS) cells from the skin cells of two individuals with autism and their family members, all from the Simons Simplex Collection. These two individuals show a larger-than-normal head circumference.

Many symptoms of autism, such as social impairments and repetitive behaviors, are accompanied by abnormal brain activity in the forebrain region. Louis Reichardt and his colleagues at the University of California, San Francisco studied the development of the forebrain, focusing on an important intercellular signaling pathway known as the Wnt pathway.

Pinpointing the specific molecular defects that cause autism is a key approach to developing appropriate treatments for the disorder. One way to uncover a disrupted molecular pathway is by identifying single-gene mutations that are associated with the disease, as has been done in Alzheimer’s and Parkinson’s. Although these mutations occur in only five to ten percent of individuals with the latter two disorders, studies have found that the same pathways are also at work in the more common, and more genetically complex disease forms.

Common variation in the human genome accounts for more than half of autism diagnoses. On an individual gene basis, however, common variation may have small effects in terms of autism risk. Researchers in the field are therefore challenged with understanding the impact of common variation on developing neurobiological circuits that are implicated in the functional symptoms at the core of autism.

Autism is a spectrum of disorders that result in aberrant development and function of the nervous system. The behavior of some children with autism improves in response to fever. Although a great deal of progress has been made in identifying genes that contribute to autism, very little progress has been made in identifying the neural cell types and circuits that are affected by mutations in these genes, or are altered in response to fever.

Many of the mutations that are known to be associated with autism disable protein complexes that support the development and function of synapses — the communication junctions between neurons. Morgan Sheng and his colleagues at the Massachusetts Institute of Technology are investigating the role of these protein complexes to learn how their loss may lead to the social and cognitive disabilities in autism.

In autism, tracing the connections between the underlying genes, altered brain function and behavioral symptoms is difficult because the disorder is caused by multiple factors in most people. Richard Tsien and Ricardo Dolmetsch of Stanford University in Palo Alto, California, Randall Rasmusson of the State University of New York at Buffalo and their colleagues study a form of the disorder linked to a single mutation, which may provide insights into the other forms of autism caused by many factors.

Early and accurate diagnosis of autism is challenging because of the paucity of biomarkers for the disorder. The neurological systems involved in social interaction — the impairment of which is a hallmark of autism spectrum disorders — offer a promising line of investigation for new biomarkers. Karen Parker and colleagues at Stanford University are undertaking the first comprehensive study to examine the relationship between oxytocin biology, one such candidate biomarker, and social impairments in individuals with autism.