Research Profile - Q&A: Tracking the onset of Autism Spectrum Disorder

Epigenetics research may unlock some of the mysteries of how autism takes hold during neurological development.

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Dr. Rosanna Weksberg is one of Canada's leading researchers in epigenetics and neurodevelopmental disorders. She leads a CIHR-funded study investigating links between autism and a process called methylation that modifies DNA strands and affects how genes are activated. The goal is to identify epigenomic errors that lead to autism. Dr. Weksberg divides her time equally between seeing patients and conducting research at The Hospital for Sick Children in Toronto. In this Question & Answer discussion, she talks about the importance of applying epigenetics to the understanding of autism and shares her excitement about potential new pathways to investigate the causes of this complex condition.

CIHR: First, a practical question. How do you manage to divide your time between the research lab and seeing patients?

RW: It's always a challenge. I do a lot of my background research and writing on the weekends and during evenings. When patients require medical attention, I make myself available. It's hard to say, 'I'm doing research today.' I specialize in issues involving growth and neuronal development – areas related to epigenetics.

CIHR: Autism Spectrum Disorders typically involve an impairment in the development of neurological processes. Is it your sense that epigenetics plays a larger role in causing ASD than just something that's malfunctioning in the genetic hard wiring?

RW: It's hard to compartmentalize it like that. The genetic factors and environmental factors impact the epigenetic marks across the genome. Such epigenetic marks determine which genes are active and which genes are silenced in a particular cell type. Combinations of environmental and genetic elements define the final epigenetic profile that ultimately drives typical or atypical developmental processes.

CIHR: What do you mean by 'environment' or 'environmental elements?'

RW: We don't actually know what the specific elements are. One of the environmental issues we are investigating is the use of assisted reproductive technology. That is our way of saying, 'OK, that's an external force that you're adding in.' We are finding more epigenetic alterations in individuals with autism who have been conceived using assisted reproduction. However we need to study a much larger number of cases to determine if there is really an increased rate of autism attributable to assisted reproduction. In order to study this issue, one would have to look at a large number of children born following assisted reproduction – for example, over 1,000.

CIHR: What other environmental factors are you looking at?

RW: Compounds such as bisphenol A (BPA) have been proposed to affect epigenetic programming. These types of compounds are currently being evaluated prospectively in cohort studies (tracking a group of individuals over time) to define their impact on epigenetic profiles in humans and animal model systems.

CIHR: When you talk about environmental factors, are you including things going on in the body with regard to the regulation of the genes during early development?

RW: Yes. There is always a background rate of epigenetic errors in early development in all individuals. One of the key players in epigenetics is nutrition and folate availability. Folate is a contributor to a chemical needed to properly epigenetically program the genome in normal development. Folate is found in many foods, but mostly in vegetables. But there's a problem: you can have too much or too little folate. It's a fine balance and depends on an individual's metabolism.

CIHR: In terms of research, what needs to be done next?

RW: We need to be able to unpack epigenetic information in relation to clinical disease. That's critical. Just the way it was done at the genomic level, it needs to be done at the epigenomic level. However, epigenomics is more complex. Unlike genetics, the epigenetic code is different from one tissue to another. You can't study blood and say the brain is the same. So that's a challenge. We also need to look at interactions of genetics and epigenetics. We know it's not one epigenetic mark involved in one disease or one gene and one disease. It's much more complicated than that. And, of course, we need to look at environmental signals and how they impact the epigenome.

CIHR: Does research into the potential epigenetic sources of ASD give you a sense of hope in dealing with these frustratingly complex disorders?

RW: Absolutely. We're very excited. We have developed new paradigms and new hypotheses to test. If a subset of epigenetic marks helps us to understand the biological basis of autism, we can target those areas for prediction of disease outcomes and potentially use them in therapeutics. If you had a potential epigenetic target, you could try to bypass it. For autism, we might be able to develop a drug or a nutrient to maximize neuronal development. So there is hope. I feel very positive about this new area of investigation.