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How early experiences can last a lifetime

by CIFAR Oct 9 / 14

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Image above: CIFAR Senior Fellow Michael Meaney (McGill University and Douglas Mental Health University Institute) Photo courtesy of the Jacobs Foundation

Meaney’s work shows parenting can produce epigenetic changes

Michael Meaney knew that many things could affect which of our genes are expressed, including different foods and chemical exposure. But what about childhood experiences such as neglect or trauma? Could they also affect the operation of our genes?

The answer is yes, and today Meaney is considered a founder of a field called behavioural genetics. His work demonstrates that early experiences can switch some genes on and others off, with profound impacts on our physical and emotional health. These effects can last for our entire lives, and sometimes throughout the lives of our children.

In recognition of the importance of his work, Meaney was awarded the Klaus J. Jacobs Research Prize, a $1.2 million prize that honours ground-breaking achievements in child and youth development. Meaney (McGill University and Douglas Mental Health University Institute) is a senior fellow in CIFAR’s program in Child & Brain Development.

“Michael’s work has been truly transformative in helping us think about the way in which early parenting and early experiences of all kinds modify our development through the molecular changes in the development of genes,” says W. Thomas Boyce (University of California, San Francisco), co-director of CIFAR’s program in Child & Brain Development and a member of the jury which awarded the prize.

Meaney is interested in epigenetics – the process by which gene expression is controlled. Epigenetic process are what make some cells turn into liver cells, and others into brain cells, despite the fact that they share exactly the same DNA. On the level of the organism, epigenetics is responsible for the fact that even if one identical twin suffers from schizophrenia, diabetes, or alcoholism, the other has a less than even chance of also developing the condition.

“Those processes are epigenetic – they signal modifications to the genome. They operate like dimmer switches. They turn some genes on and they silence other genes,” Meaney says.

Researchers prior to Meaney had shown that differences in the environment such as diet could affect which genes were turned on and off. But Meaney wanted to see if experience would do the same thing.

In one of his most important papers, he showed how different forms of mothering would directly affect gene expression in rats. When a rat mother fails to lick and groom her pups enough, the pups grow up to show increased hormonal and behavioral signs of stress.

Those pups were also less likely to lick and groom their own pups.

But the difference wasn’t genetic – it was epigenetic. When Meaney took pups from good mothers and allowed them to be reared by neglectful mothers, the pups suffered more from stress, and also turned into neglectful mothers themselves. The same happened in reverse.

To top it off, Meaney and his collaborators were able to track down the molecular mechanism behind the epigenetic changes. They found molecular changes that controlled expression of a gene that encodes for a particular kind of neuroreceptor, one associated with the stress response. In effect, neglected pups had the dimmer switch for the genes turned down, and suffered greater stress as a result.

Later, work on humans showed the same result. People with a documented history of neglectful and abusive childhoods showed the same epigenetic alterations as those in the neglected rats.

“These findings provide an understanding of how it is that the early social environment can persistently influence the function of the brain and the mental health of individuals over the lifespan,” he says.

Meaney’s findings suggest that children facing harsh early environments may carry the mark throughout their entire lives in the form of increased stress response and other problems. But it also raises the hope that interventions can reverse the process.

It’s even possible that children could be tested to see if they carry the markers suggesting they’ve been negatively affected by neglect. After all, many children who suffer neglect don’t suffer lifelong ill effects. Identifying those who do could allow us to focus resources on the children who need help the most.

Meaney credits CIFAR with helping him extend his work in important ways.

“Where CIFAR was absolutely critical was in developing the sophistication with which we could translate work from rats to humans. Our ability to do that meaningfully was largely shaped through the discussions we had with colleagues on the CIFAR network. I’ve collaborated with a number of people in the network, and of course these collaborations have shaped our science.”