The Traces of Trauma

Researchers draw links between early childhood abuse and suicide

June 1, 2015

In the mid-2000s, a Canadian researcher showed that early life experiences could have lasting effects on rat behaviour. Dr. Michael Meaney found that rat pups exhibit anxious behaviours if they receive less favourable care from their mothers, and that these behaviours were associated with changes in gene activity. This work opened up a new line of research for Dr. Gustavo Turecki, who is based at the Douglas Mental Health University Institute.

Dr. Turecki wondered whether similar results could be observed in humans. Drawing on the Douglas-Bell Canada Brain Bank for tissue samples, Dr. Turecki, together with Dr. Meaney and a third researcher, Dr. Moshe Szyf, went on to show, for the first time, that childhood abuse leaves molecular traces in the brain.

"We've known for a long time, clinically, that many people who have been abused in childhood can have a hard time regulating their emotions later in life," says Dr. Turecki, who directs a multidisciplinary team at the McGill Group for Suicide Studies (MGSS). "Little is known about the molecular mechanisms that lead to long-lasting consequences in behaviour, including suicide."

Dr. Turecki is now helping uncover these mechanisms through the emerging field of epigenetics.

"We are all born with a genetic code that is immutable," says Dr. Turecki. "Epigenetics is the science that investigates how the genome is regulated – how it adapts to stimuli, and decides which processes to ‘turn on' or ‘turn off.' The cells in a brain and a liver share the same DNA, for example, but function differently because certain genes are active, and others are dormant."

He likens the genetic code to a book with many chapters that can be read selectively. "When you're reading Chapter 10, it doesn't mean the text in Chapter 1 isn't there," he says. "Epigenetics regulates which pages are open at what times, and what ‘sentences' are magnified."

In 2009, with funding from the Canadian Institutes of Health Research, Drs. Turecki, Meaney and Szyf showed that individuals who had experienced childhood abuse had different epigenetic markings on the DNA in the hippocampus, a part of the brain involved in the formation of memories.1

"There was a lot of excitement about the project," says Dr. Naguib Mechawar, who was setting up his own lab at MGSS at the time. "The study made a lot of headlines."

Alongside their lab work to discover traces of abuse in the brains of suicide victims, the researchers conduct structured interviews with family members to piece together the victim's past. Understanding the extent and nature of the abuse or neglect helps inform the researchers' interpretation of molecular changes in the brain.

"For years, epidemiological studies told us that bad experiences and social position can lead to differential rates of morbidity (sickness) and mortality," says Dr. Stephanie Lloyd, an anthropologist working with the team. "Ultimately, [epigenetic] research is trying to throw the ‘nature versus nurture' debate out the window, and move into a co-production space where nature and nurture are constantly informing each other."

Findings in the celebrated 2009 study focused on one variant of NR3C1, a receptor involved in the brain's response to stress. Dr. Turecki's team found fewer copies of the receptor in the brains of suicide victims with a history of childhood abuse. This suggests that early life events can affect genes in a way that could heighten risk for emotional distress in later life.

The study reaffirmed previous studies on animals, and prompted the team to expand the scope of its research across the genome. In 2012, they found that early-life trauma induced alterations in DNA methylation – a type of chemical modification that affects gene regulation – in several genes.2

Evidence in Action

Drs. Mechawar and Turecki co-direct the Douglas-Bell Canada Brain Bank, which is essential to the research at MGSS. The Bank is home to tissue samples from thousands of human brains. Known for its speciality in suicide, the Bank distributes some 1,000 brain tissue samples annually to researchers in Canada and around the world. Each year, more than 20 scientific articles draw on these samples.

Without access to these samples, Dr. Turecki and his colleagues wouldn't be able to study epigenetic changes in brain tissue. But the Bank does have some limitations. Through their research on rats, Drs. Meaney and Szyf showed early life experience can shape the brain, and that some effects can even be reversed. But similar studies aren't possible in humans. "You can manipulate and expose animals to certain conditions," says Dr. Turecki. "Obviously, in humans, we can't take people in and out of abusive situations and observe the difference."

Another ongoing challenge is understanding the brains of "resilient victims" – those who experienced childhood trauma but did not commit suicide. The Bank also lacks control samples from people who had no neurological disorders.

"This makes it challenging to tackle questions as deeply as we would like," says Dr. Mechawar. "We may be excited about findings, but we know the limits of our study, and try not to go overboard with our conclusions."

The MGSS takes care to interpret their findings cautiously, says Dr. Lloyd. "If we say suicide is an outcome of methylation, it reduces the act of suicide to early childhood abuse, which I don't think anyone at MGSS would claim."

But the growing understanding of epigenetic changes could one day lead to improved treatments and interventions for people at risk of suicide. In the meantime, Dr. Turecki works hard to maintain a link between the work he does in the lab and the needs of people living with depression. Early in his career, he realized that he wanted to combine research with work as a psychiatrist.

"If I didn't have contact with patients, I became more detached from the problems," he says. "Having clinical experience helped me gain insight and generate hypotheses."

At the Douglas Institute, he follows about 250 patients who often arrive with depression that family doctors were unable to treat.

"Each person has a different story. Sometimes you can't help people, but when you can, it's extremely rewarding. That's what keeps me going."

Footnotes

Footnote 1

McGowan, P.O., et al. "Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse," Nature Neuroscience 12,3 (2009):342-348. doi:10.1038/nn.2270.

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Footnote 2

Labonté, B., et al. "Genome-wide Epigenetic Regulation by Early-Life Trauma," Archives of General Psychiatry 69,7 (2012):722-731. doi: 10.1001/archgenpsychiatry.2011.2287.

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