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A Holistic Understanding of Autism

Researchers at Duke-NUS are tackling the challenging puzzle that is Autism Spectrum Disorder (ASD) on different fronts – and working to put together a holistic and in-depth picture of how the condition develops and ways to diagnose it.

When does a child with idiosyncratic behavior or who is socially-inept meet the criteria of a condition such as ASD – and is there a better way apart from observation to diagnose the problem? What genes are responsible for ‘causing’ ASD? How do these genes affect the way the brain develops such that it causes the social behavior and, communication abilities apparent in someone with ASD?

These are some of the questions that the Duke-NUS team of researchers is working to address. Autism is a disorder caused when there is a problem with the process (called neurogenesis) that grows and shapes the development of the brain. This impairment affects the way a person communicates and relates to others and results in a lower ability for social interaction and imagination. Other common outcomes of this neuro-impairment are repetitive behavior and a poor understanding of abstract ideas. Because the level of impairment ranges, the condition is termed a ‘spectrum’.

From left: Drs. Eyleen Goh, Brown Hsieh, Shawn Je and Helen Zhou
From left: Drs. Eyleen Goh, Brown Hsieh, Shawn Je and Helen Zhou

Researchers Shawn Je, Brown Hsieh, Helen Zhou and Eyleen Goh from Duke-NUS’ Neuroscience and Behavioral Disorders Program, are tackling the different dimensions of ASD. Their work stems from the foundational research of Associate Professor Steve Rozen, who is at the school’s Cancer & Stem Cell Biology Program. He found a sequence of more than 700 genes taken from persons with ASD. This is a useful baseline from which to identify differences with control samples and to do comparisons. According to Assoc. Prof. Rozen, science has yet to pin point the causes and mechanisms of ASD. “We know that the diagnosis covers a diverse grab-bag of characteristics. We also know that ASD has a strong genetic component, but that the genetic component is also very diverse and probably involves hundreds of genes. [But] only a handful of these genes have been identified, and none accounts for more than a small fraction of ASD.”

Understanding the cellular and biological basis of ASD is important to find therapies that will enable patients with ASD to lead more independent and satisfying lives, he added. “When we find a specific gene in which mutations cause (or strongly predispose) to ASD, then we have a tremendously powerful tool to investigate the biological mechanisms underlying ASD … Genetic understanding provides a powerful tool because it lets us build so-called models -- for example, neurons or even mice that are genetically engineered to have ASD-associated genetic variants. Obviously, it is much easier to study possible drugs in cells grown in the laboratory or in mice than it is to study them in humans!”

ASD researchers having a light-hearted conversation with Assoc. Prof. Steve Rozen
ASD researchers having a light-hearted conversation with Assoc. Prof. Steve Rozen

Assoc. Prof. Rozen’s sample sequence has been the basis for Assistant Professors Shawn Je and Eyleen Goh to identify the actual genes linked to ASD, and begin further exploration into how and why these genes affect neurogenesis. “With the genetic sequence mapped, the next step is to make sense of the code and understand which genes cause which outcomes,” explained Dr. Je. This is being achieved on three different fronts. Working on different areas and tapping on the different expertise of different researchers has been beneficial, said Dr. Goh, “By working together we can look at different angles and this makes the team stronger.”

How autism develops in the brain

To gain a better understanding of the way the brain develops in cases of ASD, Dr. Goh works with ASD models to identify what kind of structural differences there are in the brain. “We grow stem cells (derived from skin samples) in culture to model an ASD neuron to monitor the development. We also can compare this sample with non-ASD controls to see how the actual disease progresses and what the delays or defects there are,” she said. The models will also mean a better way to test for effective drugs, she added.

Together with other Duke-NUS researchers, she is working to obtain a Singapore-based sample to study the local population. “We hope to recruit more people into the study so as to generate more data – a better baseline – for an Asian population. The good thing for those involved in our study is that the research is done here and they can benefit from the support and the updates.”

Making a better diagnosis

Apart from understanding the way ASD develops in the brain, another facet of research is in how to better diagnose the disease in an objective and non-invasive way, said Dr. Je, as “Early diagnosis is the key for intervention.” Currently, diagnosis is based on observation and psychological tests which are not always accurate.

Dr. Brown Hsieh, elaborated, "Based on the current neurological findings of ASD, we can make some simple predictions about how they are going to behave/perceive in certain tasks, [so] we plan to examine whether these predictions are correct, and if so, we will try to standardize these tasks to help diagnose ASD.” The test is based on testing how well the different parts of the brain communicates, as those with ASD have an impairment of a part of the brain known as the corpus callosum – an area of the brain that links the right hemisphere of the brain with the left.

A test shows two dots travelling either up and down or left and right. The person undergoing the test has to press a button when he or she sees the change in the direction. Someone who can perceive the horizontal motion has a functioning corpus callosum because the brain can communicate between hemispheres. However, people with some problems in their corpus callosum tend to perceive the up-down motion more frequently than the horizontal motion. The benefit of this approach is that even very young children can do the test easily.

Developing a picture of ASD brain function

Adding to these areas of study, Dr. Zhou uses MRI and other neuro-imaging to evaluate the brain structure and function. “We have characterized the genetic sequence, but the question is, what are the changes in the brain underlying symptoms seen in ASD such as social-emotional disruptions or repetitive behavior?” She further explained, “We hope to use multi-model neuroimaging to how different parts of the brain communicate and connect to each other. By seeking knowledge between brain measures and behaviors/symptoms in ASD, we aim to develop these neuroimaging techniques as a biomarker to perform early diagnosis and progression monitoring in ASD.”

Autism Spectrum Disorder (ASD) has been adopted by Duke-NUS as its Corporate Social Responsibility (CSR) program. The aim is to provide avenues and opportunities for our faculty, staff and students to contribute to the ASD cause in their respective capacities. While our faculty continues to leverage on their research capabilities and genetic studies on ASD, our students from the Benjamin Sheares College recently organized the World Autism Awareness Week campaign from April 2 to 8, 2013, to highlight ASD knowledge, awareness and integration. Our staff and student volunteers in the CSR program can look forward to several upcoming activities for the year, such as organized outings and regular volunteer programs, which will make a difference to the lives of individuals affected by ASD.

Light It Up Blue 2013

World Autism Awareness Week (WAAW) 2013

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