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.

Genetic factors are thought to play a major role in the occurrence of autism. Multiple genetic abnormalities have been identified in people with autism, and genetic mutations currently explain approximately 15 percent of autism cases. David Ledbetter and his colleagues at Emory University School of Medicine in Atlanta found in 2010 that the loss (deletion) of genetic material in chromosomal region 17q12 confers a high risk for autism and schizophrenia.

Some copy number variants associated with autism lead to measurable anatomical defects or exhibit ‘mirrored phenotypes,’ meaning that deletions and duplications of the chromosomal region have opposite anatomical effects. Nicholas Katsanis and his colleagues at Duke University in Durham, North Carolina, are using these observations to investigate which genes within certain copy number variants lead to neurodevelopmental traits.

Growing evidence indicates that neuronal circuit dysfunction may underlie autism behaviors, although the nature of this impairment and how it leads to autism is still unclear. Despite the fact that neuronal circuit regulation takes place at the synapses — the sites of communication between neurons — very few studies have focused on synaptic proteins and their modification.

A newly discovered genetic condition called TMLHE deficiency results in the loss of the ability to make carnitine in the body. Arthur Beaudet and his colleagues at Baylor College of Medicine in Houston, Texas, hypothesize that carnitine deficiency in the brain can cause autism, and that dietary supplementation with carnitine may prevent or reverse autism symptoms associated with TMLHE deficiency.

Children with autism spectrum disorders vary considerably in their language abilities, but even verbally proficient children have difficulty with two aspects of language: pragmatic inference, which uses context to understand the meaning of a sentence, and prosodic comprehension, which uses speakers’ tone to understand the feelings, attitude and information they wish to convey. Although children with autism have difficulty with both skills, the extent of these difficulties and their causes are poorly understood.

Growing evidence links errors in genetic control to autism. However, an emerging theme in the pathobiology of human neurologic disorders is that such errors are often found in the regulation of RNA rather than DNA. This fascinating set of observations suggests that whole-genome analysis may be complemented by new technologies that can be used to study RNA regulation. Robert Darnell and his colleagues at The Rockefeller University in New York plan to do just that.

Functional connectivity in the brain refers to the synchronization of neuronal circuits to transfer information within and between the circuits. Long-range cortical functional connectivity, which links distant areas in the cortex, is often weaker in people with autism spectrum disorders than in controls. It is generally thought, however, that local functional connectivity is stronger in people with the disorder than in controls.