Skip navigation

Calls to Action

The Emerging Biology of Autism Spectrum Disorders

Guest post by Matthew State, MD, PhD, (left), co-director of the Program on Neurogenetics and deputy chair for psychiatry research, at Yale University School of Medicine; and Nenad Sestan, PhD, (right), Yale University professor of neurobiology 

This past week, the journal Science featured our “Perspective” on recent progress in autism research and brain science. In it, we describe important new avenues for advancing understanding and ultimately treatment of autism spectrum disorders (ASD).

We wrote this article to highlight a profound change underway in the scientific opportunities available to ASD researchers. These stem from several factors. One is the rapidly accelerating progress we’re seeing in gene discovery. Another is the emergence of a detailed map of the developing brain’s molecular landscape. These are critical pieces of the puzzle. We’ve achieved them thanks to strategic investments on the part of private foundations and advocacy groups such as Autism Speaks, as well as the National Institutes of Health.

We see tremendous power in the combination of a newfound understanding of ASD genetics and a more sophisticated understanding of gene expression and regulation in the developing brain. We’re beginning to answer the questions of when, where and how brain development and processes go awry in ASD.

The past year, in particular, has delivered tremendous progress in the discovery of new ASD risk genes. This comes with greater understanding of the role played by new, or de novo, changes in the sequence of the DNA. Importantly, we are developing reliable and systematic methods to continue uncovering and understanding genetic risk factors for autism.

But gene discovery is just the first step. Our larger goal is to create the knowledge we need to develop new treatments. In our article, we highlight equally remarkable advances in our scientific understanding of the nature and variability of gene expression in the developing human brain. We describe an overarching approach to combining these scientific resources to move progress from identifying genes to understanding specific aspects of brain development to delivering real-life treatments.

For example, newly discovered ASD genes point to the importance of a wide range of biological processes in nerve cells. Despite their diversity, many of these ASD genes share the property of being turned on during the same time points and in the same regions of the early developing brain. In particular, they activate when early connections are forming in the prenatal cerebral cortex, a part of the brain critical for cognition, perception and behavior.

We know from studying animal models that these emerging brain-cell connections, or synapses, are particularly sensitive to genetic variation. We also know that these brain circuits take a long time to mature. Indeed, some are not fully developed until early adulthood. This combination of early vulnerability and extended maturation helps account for the surprising recent observation that many of the genetic regions identified as increasing ASD risk also increase risk for other developmental brain disorders such as schizophrenia. In other words, these brain circuits begin to develop early and don’t become mature for a long time. As a result, they remain vulnerable to disturbance.

Overall, we see tremendous value in looking at the growing list of ASD risk genes – not one at a time – but as a group. We must view them through the lens of what we are learning about gene expression and its regulation in the human brain. As the number of known ASD risk genes increases and our knowledge of the molecular landscape of the developing brain expand, we are seeing a new world of opportunities to identify and understand the underlying mechanisms that lead to social disabilities.

Lastly, we focus on how this emerging knowledge can be turned into new approaches to treatment. For example, recent evidence from animal models shows that targeting specific ASD genes may reverse ASD-like symptoms, even in adult animals. These observations challenge long-standing assumptions that early developmental disorders are “set in stone.” They offer hope for treating not only symptoms, but also the underlying developmental difficulties in ASD.

They also tell us that deepening our understanding of autism’s basic biology – though a long, hard and often frustrating road – has the potential to offer more effective and personalized treatments. This is just what has occurred with disorders such as cancer and heart disease over recent decades. We have every reason to hope that the next few years will bring similarly great strides in the understanding and treatment of ASD.

Editor’s note: Autism Speaks funds a broad array of research into autism geneticsbiology, gene-environment interactions and treatment/prevention. You can explore these and other studies using our Grant Search.

The Autism Speaks blog features opinions from people throughout the autism community. Each blog represents the point of view of the author and does not necessarily reflect Autism Speaks' beliefs or point of view.