Abnormalities in brain development associated with autism may be caused by abnormally high activity of the beta-catenin signaling pathway. Anjen Chenn and his colleagues at the University of Illinois at Chicago, with Eric Courchesne and his colleagues at the University of California, San Diego, aim to test the hypothesis that beta-catenin signaling levels are higher in cells from individuals with autism than in controls.

Several lines of evidence implicate the adult stem cell-containing subependymal zone (SEZ) in autism spectrum disorder (ASD). The goal of this project is to determine if SEZ stem cells and neurogenesis are altered in ASD.

There are two emerging themes in research on genetic factors contributing to autism. First, autism is sometimes associated with small deletions within chromosomes, leaving the affected individual with only one copy of a group of neighboring genes. Second, mutations in proteins at synapses (sites of nerve cell communication) can contribute to autism. Mitchell Goldfarb and his colleagues aim to test whether these two themes can be integrated.

The activation of extracellular signal-related kinase (ERK), a key enzyme in cellular signaling, may prove to be a useful biomarker in autism, as an aid in early diagnosis, a predictor of treatment response, and perhaps as a predictor of long-term outcomes. ERK is being used as a biomarker in fragile X syndrome because ERK activation is delayed in blood samples of people with the disorder, compared with controls.

Autism encompasses a range of cognitive and behavioral characteristics, and studies suggest that certain genetic abnormalities are common in individuals with autism. A major challenge is to link these genetic abnormalities with the behavioral features of autism, such as social deficits and anxiety. Gil Levkowitz and his colleagues are tackling basic questions concerning the development and function of the hypothalamus, an important yet understudied brain region.

Autism spectrum disorders share common features of impaired social relationships, impaired language and communication, repetitive behaviors and a limited range of interests. Although monogenic disorders collectively account for a minority of autism cases (10 to 15 percent), the molecular alterations in these disorders could reveal common pathways shared by disorders across the autism spectrum.

Abnormal brain wiring during early development may be a causal factor in autism spectrum disorders. Brain wiring requires the guidance of neuronal fibers (axons) to the appropriate brain regions, as well as the establishment of functional synapses — key points of communication between neurons.

Contactin-associated protein-like 2 (CASPR2, encoded by the gene CNTNAP2) is a cell adhesion molecule that is essential for proper neuronal function. Common and rare genetic variations in CNTNAP2 are associated with an increased risk of autism spectrum disorders. A recessive mutation in exon 22 of the gene causes a syndromic form of autism called cortical dysplasia-focal epilepsy syndrome (CDFE). CDFE is a common cause of intractable epilepsy in children, and the cerebral cortex of individuals with CDFE often shows a disorganized structure.

Stelios Smirnakis and his team at Baylor College of Medicine in Houston, Texas, worked to understand how genetic defects in autism lead to malfunction at the circuit level. Understanding the mechanism of circuit malfunction will help generate new hypotheses on how to intervene to promote recovery.

Autism spectrum disorders and fragile X syndrome have a remarkable clinical association and share biological ties to the molecular pathways critical for communication between brain cells, at synaptic junctions. Although a large number of genes have been implicated in autism, fragile X syndrome is caused by the loss of a single gene that encodes FMRP, a protein that regulates many messenger RNAs (mRNAs) before they are expressed as proteins.