Chromosomal microarray (CMA) analysis to detect copy number variations (CNVs) —duplication or deletion of chromosomal regions — is the recommended first-tier diagnostic screen for autism, and studies of structural variation (SV) to date have largely focused on CNV detection and interpretation. Copy-neutral SVs, or balanced chromosomal abnormalities (BCAs), have not been systematically surveyed in autism, suggesting that these rearrangements could represent a potent class of loss-of-function mutations that have not yet been characterized in autism.

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.

To understand the neurobiology underlying autism spectrum disorders, more data at the cellular level are needed. This is difficult to obtain from living individuals. However, physiological data can be collected directly from cells in the human brain (i.e., neurons) during neurosurgery for medically refractory epilepsy. Two methods can be used in these cases: depth electrode recording and surface grid monitoring.

Although intellectual impairment is not one of the diagnostic criteria for autism spectrum disorders, half or more of all people with autism have an intellectual disability. Intellectual disability can present an equal or greater challenge to individuals with autism than do autism-specific deficits. To date, the intelligence quotient (IQ) is one of the best predictors of response to treatment among youth with autism, and it is also one of the best predictors of long-term outcomes.

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.

A hallmark of autism spectrum disorders is impaired social interactions. Several studies show that neural systems that support social interaction overlap with those responsible for the perception of reward. The poor responsiveness to social stimuli seen in individuals with autism could therefore reflect a failure to attribute reward value to social interactions.

Many single-gene disorders linked to autism affect proteins that modulate the translation of messenger RNA into proteins that function at synapses, the junctions between neurons. A few examples are FMRP in fragile X syndrome, TSC1 and TSC2 in tuberous sclerosis complex and PTEN in Cowden syndrome. This led Mark Bear at the Massachusetts Institute of Technology and Raymond Kelleher at Massachusetts General Hospital to propose that ‘troubled translation’ is a core pathophysiological mechanism underlying autism spectrum disorders.

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.