Research Profile - The scars of abuse
Dr. Michael Meaney
Dr. Gustavo Turecki
Three of Canada's leading epigenetics researchers are investigating how childhood abuse and neglect can mark DNA molecules in the brain cells, leaving victims more vulnerable to mental health challenges and suicide.
Abuse or neglect can scar the brain of a child as much as smoking can damage the lungs of an adult, says McGill University's Dr. Gustavo Turecki.
As with tobacco, abuse can take a long time to inflict damage that ultimately may prove to be fatal.
At a Glance
Lead Investigators – Drs. Gustavo Turecki, Michael Meaney and Moshe Szyf of McGill University.
The approach – Initially, the investigators studied Quebec Brain Bank specimens of 36 brains (12 suicide victims who were abused, 12 suicide victims who were not abused and 12 controls). They focused on essentially one variant of one gene in the hippocampus and found different epigenetic markings among those the abused group.
What's next? – The study has been expanded to three times the original sample with investigators looking beyond the hippocampus into the neighbouring region of the anterior cingulate and examining other variants.
Findings – "We found a number of other genes that are differentially methylated in individuals who were abused in childhood," says Dr. Turecki. "[These genes] primarily were related to neurogenesis – how neurons divide and grow."
"As much as inhaling smoke can dramatically impact and change lung cells, absorbing very strong traumatic experiences can change the epigenetic regulation of critical genes in the brain," says Dr. Turecki, a psychiatrist at Montreal's Douglas Mental Health Institute.
Working with McGill colleagues Drs. Michael Meaney and Moshe Szyf, Dr. Turecki leads a five-year project funded by the Canadian Institutes of Health Research (CIHR) to investigate links between the genetic effects of environmental stress and mental health. The investigators' 2009 paper in Nature Neuroscience demonstrated for the first time that negative life experiences in childhood can lead to epigenetic alterations in the brain that increase the likelihood of a person committing suicide.
"That study was focused on one gene known as neuron-specific glucocorticoid receptor (NR3C1) that codes for the glucocorticoid receptor in the hippocampus region of the brain," says Dr. Turecki. This gene is critical in fine-tuning an area of the brain that, among other things, regulates moods and emotions.
While the research was originally limited to the equivalent of one variant of NR3C1 called 1F in one part of the brain, the investigators have since expanded the scope of their research. "We wanted to know if there are other genes equally important as NR3C1," says Dr. Turecki. "Are there differences in the methylation (a key DNA modifying process involved in gene regulation) of other NR3C1 variants and genes? Is this phenomenon limited to the hippocampus or does it also take place in other parts of the brain?"
The innovative work underscores the key role that epigenetics, which Dr. Turecki describes as the body's way of "fine-tuning" its genetic code, plays in mental health.
"A code is inscribed in the genome that we inherit from our parents," says Dr. Turecki. "This code functions in a very fixed manner. If the code says you're going to have blue eyes, then you're going to have blue eyes. But if we only had a fixed code it would be very difficult for us to adjust our needs to the physical and social environments in which we live. Maybe there is something you will need if you live in Environment A, but if you live in Environment B you don't need it or you need only half of it. There are a number of mechanisms that regulate, adjust and fine-tune the code, and one of the most important is epigenetics."
The Impacts
Dr. Michael Meaney says epigenetic investigation into the functioning of the human brain can have profound effects on public policy, clinical practice and basic biomedical research:
Public policy: "The research suggests there is a very real biological basis to the relationship between childhood abuse, maltreatment and family function on the one hand, and health and productivity of the offspring on the other hand. What we're doing is to define and create plausibility for the scientists who have argued that the function of the family is critical to determining the health and welfare of the children."
Clinical practice: "When you then start to think of gene-environment interactions, the question becomes: what, biologically, is the mechanism by which an environment may alter the functioning of the genome? What our studies provide is insight into how that might occur. We can now start understanding those epigenetic marks as a dynamic reality that can be a substrate for intervention."
Biomedical research: "What occurs in the context of epigenetic studies is we start to think of the DNA molecule as subject to regulation, to structural and functional changes over time by virtue of environmental forces. We think of DNA not so much as the starting point from which all other variations in biology emerge, but in part as the target of regulation itself."
"Child abuse sends a very strong message to the brain and all the other systems saying, 'This is the kind of world you live in – rearrange yourself to adapt.' That adaptation can become maladaptive in the wrong context. Perhaps an important fraction of mental illnesses and other diseases are essentially maladaptations. If we understand the principles of the adaptation we might be able to sort out the maladaptations."
Dr. Moshe Szyf, McGill University
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