Multiple autism spectrum disorders share similar neuronal deficits at the molecular and cellular levels. Understanding the mechanism underlying those deficits helps researchers identify valuable targets for therapeutic development.
The proposed research takes advantage of the resources available at the University of Oxford in the U.K. to validate a new noninvasive magnetic resonance imaging (MRI) biomarker of autism using postmortem imaging. This has enormous potential for subsequent development as a tool for early detection, diagnosis, monitoring and assessment of individuals with autism. Steven Chance and his colleagues seek to better understand the cause of autism by investigating the neuroanatomical basis of the condition. Accurate diagnosis in life is difficult because the detailed changes in the cerebral cortex cannot be seen in brain imaging of living people.
Choline is an essential nutrient for all animals, including humans. Prenatal and early postnatal supplementation with choline has been shown to enhance long-term cognitive performance, improve motor deficits in a mouse model of Rett syndrome, and reduce the adverse effects of neonatal alcohol exposure in rodents.
Autism spectrum disorders represent a challenge for geneticists because of the heterogeneity of causes. Still, in a subset of people with autism, certain deleterious gene mutations have been identified, and most are involved in the formation of synapses — the points of contact between neurons. At first, these mutations alone were thought to be sufficient to cause autism, but studies suggest that the inheritance of ‘modifier genes,’ which alter the expression of other genes, might contribute to the wide behavioral variability observed in individuals with autism.
Most research into autism spectrum disorders has focused on genetic, behavioral and neurological aspects of the illness, but people with autism also show striking alterations in immune status.
Autism genetics has made demonstrable progress in the past few years with the recognition of the role of de novo, or spontaneous, copy number variants (CNVs), loss-of-function point mutations and common inherited DNA variants. Although landmark studies have proved the important role of genetics, the common and robust finding is twofold: Hundreds of genes contribute to autism pathogenesis, but owing to limitations of statistical power and sample size, only a tiny fraction of them can be conclusively identified.
Few robust biomarkers have been identified for autism, and there are no medications that treat the social deficits associated with the disorder. Progress has been impeded in part by the challenge of obtaining relevant tissue samples from people with autism and matched controls.
Autism is a neurodevelopmental condition with a strong genetic basis, but a gap in knowledge exists between genetic and behavioral phenotypes due to a lack of neurophysiological explanation. To bridge the gap, Hiroki Asari aims to characterize and rescue changes in visual processing in autism model mice using causal experimental tools in modern systems neuroscience.
Like autism, Rett syndrome arises in young children with a progressive loss of skills such as speech and control of movements, and is frequently accompanied by mental retardation and seizures. Mutations in the gene MECP2 are known to cause Rett syndrome. Josh Huang and his colleagues at Cold Spring Harbor Laboratory plan to study how the MECP2 gene regulates brain circuitry — information that may have implications for both Rett syndrome and autism.