The mystery of childhood mental health

How can we identify who is at risk?
Michael Meaney

Neurobiologist Michael Meaney talks about a life spent puzzling how our genes and environment interact and affect our brain development. He also explains why he is determined to discover how early circumstances might dictate children’s mental health.

Could childhood mental health one day cease to be a mystery? Is a child’s long-term happiness determined before he or she is even born? How can we identify and help children who are vulnerable?

These are questions which keep Michael Meaney up at night. Meaney’s research looks at long-term effects of early experience on gene expression; in other words, how our first years – and our parents’ behaviour – shape our brain function. Back in the 1990s, Meaney and his team examined differences in how mother rats care for their pups. They were able to identify the biological mechanisms by which rats’ maternal behaviour caused long-term change among their offspring.

Their startling finding was that interaction between a mother rat and pup alters the expression of genes that determine in the long term how that pup responds to stress. Meaney and his team were then able to show the same response in humans, demonstrating  that early childhood experiences leave biochemical markers on an individual’s genes, and thus have a long-term effect.

Helena Pozniak: You’ve recently been researching why some children thrive in adversity, while other suffer. What is your motivation?

Michael Meaney: You encounter children who are suicidal at the age of six. What has made them this way is already embedded. You need to get to them, and their families, before this occurs. Other conditions are recoverable but poor mental health is so pervasive, it wrecks lives, it causes other forms of disease. As paediatricians, we can’t yet get to the affected children early enough to prevent these outcomes.

HP: Your work has given a biological framework for understanding interaction between nature and nurture – what does this mean?

MM: Our interest has been not simply how the environment produces an immediate effect on traits but how it produces long-term effects. How is it that events become embedded in biology? Today this sounds trite, but 15 years ago it was important to tell policy makers that early life events can have profound, long-term effects on children’s health and quality of life. We gave evidence of how parental effects can occur and be stable. It has brought development science back into the picture.

“Poor mental health is so pervasive, it wrecks lives, it causes other forms of disease. As paediatricians, we can’t yet get to the affected children early enough to prevent these outcomes.”

HP: You’ve said the nature-nurture debate is out of date – what do you mean by this?

MM: Epigenetics – the study of biological mechanisms that switch genes on and off – approaches one of the most fundamental questions we have about human nature:  What are the forces that define who we are and why we are different from other people? Historically, beliefs have fallen in two camps: those who believe that biology – our genes – dictate why we are different. The opposing camp believes it’s the environment we live in that shapes who we are. But as Donald Hebb, who’s considered the founder of modern neuroscience, says; it’s like asking what contributes more to the area of a rectangle – the length or the width? The very activation of a gene is a product of environmental signals. And it’s impossible to disentangle them.

HP: You study how early experience affects us – how early?

MM: We looked at cord tissue in newborns and at the regions in the genome that show differences in methylation across individuals.  In 85 percent of cases, these differences are most tightly explained by an interaction between the genetic sequence and the environment. So that difference has already been established in the womb. In the early days of child development, it was common to believe that nothing terribly important happened before birth in terms of environmental influences. This is clearly wrong, and is a hot topic now – the idea that the prenatal environment can be so influential.

HP: How much do we know about what affects babies in the womb?

MM: Researchers are currently looking at how the inter-uterine environment might produce long-term effects. Some researchers are looking at nutrition, and this links to work we are doing in Singapore. We’ve looked at a mother’s nutritional status and found that lipids in the blood – particularly free fatty acids – are not only associated with a mother’s mood, which was already known, but are also highly predictive of behavioural outcomes in children.

“How well you do in school at 16 has already been determined by a very young age.”

Elsewhere, researchers are examining the effects of stress hormones and of inflammatory signals produced during the course of an infection in pregnancy. And one exciting strand of research examines how much is determined right at the earliest formation of the embryo.

HP: What are you hoping to achieve?

MM: My paediatric colleagues already know most mental health problems surface early in life. How well you do in school at 16 has already been determined by a very young age. Doctors know that if they are going to prevent these problems, they need to identify high-risk children sooner. I want to be able to turn to my colleagues in paediatrics and tell them who’s at risk of mental health problems. But we are not there yet, and it troubles me that we can’t take our work and use it to predict reliable outcomes.

HP: Why are you focusing on mental health?

MM: The brain has always been my particular interest. Mental health is the most prevalent problem in our world – the World Health Organisation confirms depression is the leading cause of disability across the globe. If a 10-year-old has type 1 diabetes, that is a challenge, but he or she lives with it. Children at that age who get depressed may fail school, stop sport, not make friends – their life is derailed. It sets the stage for a life of misery. But there’s no point saying a ten-year-old is at risk of mental health problems – by the time it’s obvious, you’ve already missed the boat as far as prevention is concerned. It is all so much more difficult to change course after this period of childhood.

“There’s no point saying a ten-year-old is at risk of mental health problems – by the time it’s obvious, you’ve already missed the boat as far as prevention is concerned.”

HP: What new research are you proposing?

MM: We are recruiting 10,000 mothers in very early stages of pregnancy, and by the time they are in the third trimester we’ll know who’s depressed and who’s not. From this we will identify a stratified group of some 1500 mothers and ask if we can follow their offspring closely until the age of four. Singapore is a very science-oriented country so we hope at least half of the mothers will agree. We want to identify the pathways that determine which children are most affected by the depressed or anxious state of the mother.

HP: What will you measure and for how long?

MM: My team and I want to focus intensely on that period between zero and age four. We want the flexibility to incorporate new technology as it emerges. In the past, we’ve just relied upon asking the mother how her child is doing.  But with this study, we aim to image their brains soon after the babies are born. Happily, newborns are easy to image – the vibrations of the machinery send them to sleep. We’ll use wearables (we’re working with Fitbit) to measure sleep, activity and heart rate: T-shirts with integrated biosensors and patches that can measure stress hormones over a given time. We can use an electroencephalogram (EEG) headband at home to monitor brain activity. We want to explore what technology can offer.

“We hope to paint a detailed picture of which individuals are vulnerable.”

We’ll also measure epigenetic variations in kids and their mums. We don’t expect to find any smoking gun. But we hope to paint a detailed picture of which individuals are vulnerable.

HP: How long will your study last?

MM: We’ll follow the children closely until they are four. But we’ll continue to collect data. We have to – for something to be a predictor, you need an outcome, and this can only be measured in late childhood to adolescence. So we are in this for the long term.

Michael Meaney is the Director of the Translational Neuroscience programme at the Singapore Institute for Clinical Sciences and Professor of Paediatrics at the National University of Singapore. He is also a Professor at McGill University in the Department of Psychiatry. His research focuses on the following questions: How do genes and environment interact to produce individual differences in brain function? Why are some individuals more affected by adverse life circumstances? Is it possible to determine an individual’s susceptibility to certain environmental influences by looking at that person’s biology, and can interventions reduce or even eliminate that susceptibility?

Michael Meaney is the 2014 recipient of the Klaus J. Jacobs Research Prize.

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