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.

People with autism spectrum disorders often lack self-awareness, making it difficult for them to interact and empathize with others. Using new genomics methods to study the neurons that are active during self-awareness and empathy, John Allman and Barbara Wold of the California Institute of Technology are learning how these processes are different in people with autism.

A major challenge facing autism research is the lack of objective measures to characterize the disorder’s various phenotypes. More quantitative phenotypic measures, derived objectively from biological measurements, would facilitate genetic association studies by allowing biologically heterogeneous populations to be categorized into subgroups. They could also help refine diagnostic procedures.

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.

The unusually high incidence of cranial and facial anomalies among people with autism may provide insight into the underlying biology of the disorder. Curtis Deutsch of the Eunice Kennedy Shriver Center at the University of Massachusetts Medical School and his colleagues are evaluating these anomalies using new, state-of-the-art imaging technology.

Recent studies have implicated a growing number of genes in the development of autism, but the candidates form a motley collection. Understanding what these genes have in common and how they relate to clinical findings in children with autism will shed light on the biological mechanisms underlying the disorder.

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.

Studies focusing on specific genes have made limited progress in unraveling the complex genetics of autism spectrum disorders. Evan Eichler and his colleagues at the University of Washington plan a broad and systematic approach to uncover autism-linked genes by scouring the fragile regions of DNA for sporadic, non-inherited deletions or duplications.

Individuals with autism find it difficult to regulate their emotions and interact with others. There is some evidence that the severity of these difficulties is influenced by higher serotonin levels in the brain. Kevin Pelphrey and his colleagues at Yale University plan to use a specialized brain imaging technique to examine the relationship between variants in the serotonin transporter gene and behavioral difficulties in individuals with autism.