Duplication of a small segment of human chromosome 7 has been found in some children with autism. Lucy Osborne and her colleagues at the University of Toronto aim to understand the effects of duplication of this region, 7q11.23, on the growth and function of the brain. They plan to study this using a mouse model with a similar duplication.
Autism spectrum disorder is widely regarded as one of the most severe childhood psychiatric conditions. The root causes of this disorder have generally been viewed as either genetic or environmental. The interaction between genetic and environmental factors has not been investigated widely, however, despite the fact that synergistic effects have been found for other neurodevelopmental disorders such as depression.
Autism spectrum disorders are a clinically heterogeneous group of disorders that share common features. Only an estimated 10 to 15 percent of autism cases are monogenic — caused by mutations in a single gene — but the molecular alterations in these disorders could reveal common pathogenic mechanisms shared across the spectrum.
The underlying causes of autism spectrum disorders are poorly understood, but one appealing hypothesis is that an imbalance of excitation and inhibition in the brain’s cortex underlies a significant proportion of autism cases.
The neurobiology behind the classic signs of autism — repetitive behaviors, impaired social interactions and language deficits — is largely unknown. Based on their studies on a mouse model of obsessive-compulsive disorder, Guoping Feng and his colleagues at Duke University propose that an imbalance between two circuits of neurons may underlie the repetitive behaviors associated with autism.
The Simons Simplex Collection (SSC) is a rigorously characterized set of data drawn from 2,700 families, designed to enrich the discovery of rare and de novo events in autism spectrum disorders. Twelve clinical sites in North America provided data from families who have one child between 4 and 18 years of age with an autism spectrum disorder. Data from each family also include information about unaffected siblings and unaffected biological parents.
Impairments in social communication are among the core symptoms of ASD, but at present, there are no validated tools that can be used to evaluate social communication outcomes in clinical trials. Researchers from three sites across the United States will validate two newly developed treatment outcome measures — the Brief Observation of Social Communication Change (BOSCC) and Elicitation of Language Samples for Analysis (ELSA) over the course of an ASD behavioral intervention trial (JASPER).
Tsai will delineate contributions of cerebellar dysfunction to autism-related behaviors in mice and assess benefits of cerebellar neuromodulation to treat these behaviors.
GRIN disorders are rare neurodevelopmental genetic conditions that alter genes that encode NMDA receptor subunits. Stephen Traynelis and colleagues plan to understand the natural history, incidence and full spectrum of clinical and functional consequences of variation that lead to GRIN disorders. This multi-dimensional dataset will be compiled and shared in a fashion that will help to catalyze the development of new therapeutic treatment strategies.