Cannabinoid treatment for the symptoms of autism spectrum disorder

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory–motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.

In this Review, Salter and Stevens discuss the role of microglia in CNS disorders such as autism, neurodegenerative disorders, Alzheimer’s disease, and chronic pain.