Autism is most likely caused by changes in the development of the cerebral cortex, particularly in neural circuits that process social and cognitive information. Under- or over-connectivity in these circuits has been found in the brains of children and adults with autism. It remains unknown how altered development might lead to these disrupted connections. This knowledge is crucial for new diagnostic, preventive and therapeutic approaches in autism.

A small protein called ubiquitin is added to other proteins to modify their function, causing changes in cellular behavior. Often, the addition of ubiquitin leads to the complete destruction of the tagged protein. This process, called ubiquitination, plays an important role in regulating the abundance of many proteins at neuronal junctions, or synapses, including receptors within the postsynaptic density (a brain region that contains receptors and other proteins that regulate neuronal function).

Over the past few years, studies have linked many genes to autism. With these discoveries comes the possibility of developing therapeutic approaches, but where to start? Alex Parker and his colleagues at the Centre Hospitalier de l’Universite de Montreal hope to use the worm C. elegans to find molecules that may be early drug development leads to help treat autism spectrum disorders.

Albert Basson and his colleagues at King’s College London plan to study the function of the CHD8 gene in brain development. CHD8, which encodes a protein that changes the structure of chromatin, has emerged as one of the most significant autism-associated genes. In vitro studies — studies conducted in an external environment — have suggested that CHD8 might function as a regulator of the developmentally important WNT signalling pathway, but whether this activity is relevant to CHD8 function during brain development is not known.

Studies since 2010 have identified a large number of genes that, when mutated, cause autism. One can group the products of these mutated genes into two categories: proteins located at the synapses, or functional connections between nerve cells, and proteins located in the cell nucleus.

KATNAL2 is a recently identified autism gene that is predicted to code for a microtubule-severing enzyme. However, researchers don’t know how this gene is involved in brain development or what cellular events in the developing brain go awry if it is mutated. Xiaobing Yuan and Peter Baas are studying whether KATNAL2 and other autism genes play an essential role in neuronal migration through the regulation of microtubule dynamics.

Accumulating evidence suggests that autism spectrum disorder symptoms arise from a disruption in the process of experience-dependent synaptic plasticity that normally occurs during critical periods of development. Critical periods are windows of time when appropriate sensory, motor and cognitive function are essential for the refinement and tuning up of brain circuits. Rett syndrome is recognized as one of the clearest genetic examples of autism, and is caused by mutations in the MeCP2 gene.

Fever or fever-associated illness in children with autism is reported to result in temporary relief of cognitive and behavioral symptoms. It remains unknown, however, which aspects of this phenomenon — such as temperature increase, immune activation, type of pathogen or type of autism — are important for this benefit to occur.

Genetic and neuroimaging studies provide strong evidence that the gene CNTNAP2 (also known as CASPR2) is a critical risk factor for autism spectrum disorders. CNTNAP2 encodes a protein on the surface of neurons that is involved in interactions between neurons and glial cells in axons with a myelin sheath.