Co-Director, Douglas – Bell Canada Brain Bank (Suicide Studies), Douglas Mental Health University Institute; Head, Depressive Disorders Program, Douglas Institute; Director, Réseau québécois sur le suicide et les troubles de l’humeur et troubles associés (RQSHA); Bell Senior Fellow in Mental Health.
Understanding suicide on a neurobiological level
Almost all of us get ‘the blues’ at some point in our lives, yet, for some, mild depression can spiral into major depression, suicidal thoughts and eventually even suicide.
Indeed, attempted and completed suicides are major problems in our society, making the understanding, prevention, and treatment of suicidal behaviours a top priority for Canadian mental health professionals.
Individuals who suffer from major depression are especially at risk. Yet, why do some people who become depressed commit suicide while others with the same illness do not?
This simple question belies the complexity of the human brain and the depths to which mental health researchers like Dr. Gustavo Turecki are plumbing the brain in order to better understand these individuals.
“We still don’t understand very well ‘the how’ of why people are depressed, most especially at the molecular level,” says Dr. Turecki, the Chair of the Department of Psychiatry at McGill University and Head of both the McGill Group for Suicide Studies and the Depressive Disorders Program at the Douglas Mental Health University Institute.
As both a clinician and neuroscientist, Dr. Turecki’s award-winning research focuses on issues such as early development, personality traits and neurobiological factors, with particular attention to how the environment interacts with the genome to increase suicide risk.
A molecular breakthrough sheds new light on suicidal behaviour
Among his major contributions, published in more than 300 peer-reviewed publications and book chapters, is the first description of the long-term impact of childhood abuse on the brain, particularly how it affects the activity of key genes involved in stress-response. More specifically, Dr. Turecki uncovered that early-life adversity epigenetically regulates the glucocorticoid receptor gene – a key component of stress response.
Scientists have known for a long time that traumatic life experiences, particularly those that occur during childhood, influence the development of psychiatric disorders. They also know that genes, such as those responsible for the stress response, play a major role in the manifestation of these disorders.
What they did not understand were the biological mechanisms through which life experiences change the expression of these genes.
Turecki’s groundbreaking 2009 study, conducted in collaboration with fellow researchers Michael Meaney and Moshe Szyf, went a long way to reconciling the persistent ‘nature vs. nurture’ debate regarding the relative influences of genes and environment on behaviour. Using the brains of people who had committed suicide, the study showed that mistreatment experienced during childhood causes lasting changes in stress-response genes.
The discovery was published in March 2009 in the prestigious journal Nature Neuroscience. It also gathered significant international attention and led to Dr. Turecki’s selection as the 2009 scientist of the year by Radio Canada/Canadian Broadcasting Corporation.
While primarily working with the donated brains of suicide victims, Dr. Turecki also conducted extensive interviews with victims’ family members and analysis of pertinent medical and social services files in order to help characterize and qualify the experience of the suicide victims.
“There have been some very rewarding moments in my life where I feel that the work I have done has made a real difference,” he says. “This was definitely one of them. I received thousands of letters from individual and families to thank me for helping them make sense out of something that didn’t make sense to them before.
Some people are severely abused during childhood. They have lifelong difficulties regulating their behaviours and have a lot of problems that they associate with that history and experience. As much as they may want to, it is very difficult to change those patterns of behaviour.
“My work has helped victims of abuse understand that their brain changed as a result of the abuse and that these changes had an impact on their behavior,” says Dr. Turecki. “Although we cannot yet easily modify such changes, just the understanding of what is wrong and why has, in many cases, been very helpful and facilitates self-acceptance.”
Predicting treatment response for depressed patients
In June 2014, Dr. Turecki and his team discovered that a tiny molecule, miR-1202, is a potential biomarker for depression and helps detect individuals who are likely to respond to antidepressant treatment.
“Using samples from the Douglas Bell-Canada Brain Bank, we examined brain tissues from individuals who were depressed and compared them with brain tissues from psychiatrically healthy individuals,” says Dr. Turecki. “In our clinical trials with living depressed individuals treated with citalopram, a commonly prescribed antidepressant, we found lower levels of microRNA miR-1202 depressed individuals compared to the non-depressed individuals before treatment. "Clearly, microRNA miR-1202 increased as the treatment worked and individuals no longer felt depressed”
This discovery may provide a potential target for the development of new and more effective antidepressant treatments.
“Although antidepressants are clearly effective, there is variability in how individuals respond to antidepressant treatment,” says Turecki. “We found that miR-1202 levels are different particularly among those patients who eventually will respond to antidepressant treatment.”
Dual role serves the patient
Turecki’s ongoing research endeavours have a strong impact on international neuropsychiatric research. His contributions in creating and managing the Suicide Brain Bank has allowed researchers from around the world to access unique and valuable human tissues. His clinical intervention protocols developed through the Douglas Institute’s Depressive Disorders Program have meanwhile helped patient care for individuals who are suffering from major depression and/or severe forms of other depressive disorders.
Dr. Turecki believes that his role as both a researcher and a clinician has allowed him to bring together basic neuroscience research and clinical work.
“You cannot be half a clinician and half a researcher, you have to do both whole-heartedly,” he explains. “There is a clear benefit to research when it continually brings you back to the reality of what you are researching – the suffering and quality of life of the patient.”
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