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.

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.

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.

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.

Electrical signals in neurons rely on the proper function of voltage‐gated sodium channels. Mutations in the gene SCN1A, which encodes voltage‐gated sodium channel type 1 (Nav1.1 channels), cause Dravet syndrome — a severe childhood neuropsychiatric disorder characterized by epilepsy, cognitive deficits and autism‐like behaviors.

Autism can be caused by a number of different genetic alterations, some of which result in known syndromes. In 2011, a genetic study of a large sample of children in the Simons Simplex Collection, a database of genetic and clinical information from families that include one child with autism, showed a strong association between duplication of the Williams syndrome chromosomal region (7q11.23) and autism.

Angelman syndrome is a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, seizures and the absence of speech, and it shows a high comorbidity with autism. The syndrome is caused by maternal deletion or mutation of a single gene that encodes ubiquitin protein ligase E3A (UBE3A). The paternal copy of UBE3A typically is silenced in neurons, and therefore the loss of maternal UBE3A results in a complete absence of the protein in most areas of the brain. UBE3A is an enzyme that targets proteins for degradation, a process that maintains normal functioning within cells.

Dennis Wall and his colleagues used machine learning to study gold-standard instruments used for assisting the diagnosis of autism. They learned that the number of behaviors that clinicians must assess to arrive at an accurate diagnosis may be far smaller than what is used today. Wall and his group hypothesized that this small number of behaviors, when run through a machine-learning classification tool, would provide a ‘digital phenotype’ that clinicians could use to better manage children on their waiting lists with risk for developmental delay including autism.