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Gustavo Turecki: Detective of the mind

Born in Argentina and educated in Brazil, a dedicated psychiatrist investigates the causes of suicide

McGill University Turecki: “Psychiatric disorders work as a trigger for suicidal behavior”McGill University

Very early in his career, psychiatrist Gustavo Turecki chose to focus his research on a grim problem that most people avoid talking about: suicide. His attention was originally attracted to the subject by a social phenomenon. In the early 2000s, the rate of self-inflicted deaths was felt to be running rampant in the province of Quebec, Canada, where he had recently moved. “I was beginning to work as a psychiatrist and I felt a need to try to understand why some people who develop depression take their own lives, while others don’t,” the researcher recalls. He hasn’t yet found the answer, but during almost 20 years of investigations he has become one of the world’s leading scholars on the subject, with more than 500 scientific articles published on the biological, social, and behavioral factors associated with suicide.

Turecki was born in La Plata, Argentina, and at the age of ten immigrated to Brazil with his father, an Argentine engineer, and his Brazilian mother. He graduated with a medical degree from the São Paulo State Medical School—now the Federal University of São Paulo (UNIFESP)—before going on to earn his doctorate at McGill University in Montreal, Canada, where he now heads the Department of Psychiatry and the Douglas Research Centre, whose mission is the investigation of mental health problems.

In a video call in early November, Turecki, 55, talked about the causes of suicide and how to reduce the problem. In April, he plans to return to Brazil to participate in the Brazilian Congress of Psychiatry and speak about his most recent research.

Suicide is a taboo topic. Why is it so difficult to talk about?
Because it has always been condemned historically and socially. No society, past or present, has supported suicide as a method of death. It’s a sin in every religion. In some, those who commit suicide can’t be buried with other people. Death by suicide is not accepted by society. This is partly because, as organisms, we were programmed to live, not to die, and in part, because it’s seen as a voluntary act. Once it’s understood that this behavior isn’t related to a lack of self-control, that a person who commits suicide is not in full possession of their free will, except in cases of assisted suicide, the picture changes.

So thinking of suicide as a voluntary act is, in a way, biased.
Exactly. I understand suicide as a result of cognitive changes associated with mental illness.

Is this view accepted by health professionals?
It’s generally understood that it’s not an issue related to self-control. I believe that today no one doubts that, in most cases, it’s associated with mental illness. However, there is a debate in the academic literature about the impact of mental illness on suicide.

There’s still discussion on how much of a factor psychiatric disorders play in this behavior.
Some studies show that the percentage of people who die by suicide and also who have symptoms associated with mental illness can vary widely. In China and India, this proportion is lower than in Western countries, and the reasons for this difference are under debate. The question isn’t whether a close association with mental illness exists, but how much of the behavior is explained by it. Nor can everything be reduced to mental illness. It is only one aspect, a risk factor. In the model I developed, I propose that psychiatric disorders act as the triggering factor for suicidal behavior, but there are other factors associated with predisposition.

Could you give examples?
First, it’s necessary to understand that there isn’t one single explanation for why people commit suicide. The risk of suicide results from a complex interaction of biological, clinical, psychological, social, cultural, and environmental factors. The relative importance of each factor varies from one individual to another. People who commit suicide have a certain predisposition, which is influenced by genetic characteristics, lived experiences, and personality. These factors interact with other aspects temporally more proximate to the act, which function as triggers for the suicide crisis. Mental illness is one trigger. Most people who die from suicide have depression. One way to understand suicide risk is to think about it like this: there are people with a certain predisposition to commit suicide who at some point become depressed and, due to that depression begin to have suicidal ideation, which can lead them to act. This model helps to understand risk, especially among younger individuals. In the elderly, suicide is more associated with mental pathology. Almost 100% of people over 65 who commit suicide have a depressive episode associated with death.

One predisposing factor that significantly increases the risk of suicide is abuse suffered in childhood

How did you arrive at these numbers?
To study the reasons associated with suicide, we often use a process called psychological autopsy. We interview relatives and others who were very close to the person who died, to try to reconstruct what happened before their death and verify symptoms of mental illness. Some studies using this technique have indicated that almost 90% of people who commit suicide went through an episode of some type of mental disorder immediately before their death. Among people under 25, the average is lower, around 50%. The proportion varies between countries. In the United States and Canada, it’s close to 90%. In China it’s 60%. One possible explanation for the difference is that sociocultural factors can hinder the accurate diagnosis of mental health problems.

One of your most cited works, published in 2009 in the journal Nature Neuroscience, shows that the brains of people who were abused in childhood respond differently to stress, which could facilitate suicide. How did you come to that conclusion?
One of the most important predisposing factors, which is not specific to suicide but significantly increases the risk, is abuse in childhood, whether it was physical abuse, sexual abuse, or parental neglect. In clinical practice, it’s been observed that people who suffered abusive experiences early in life are at higher risk of manifesting suicidal behavior and dying from suicide. This is also well established in the scientific literature. Our studies suggest that this risk is related to difficulties in regulating emotional and behavioral responses. These people tend to be more impulsive and aggressive. In general, they are more explosive. They also tend to be more anxious. The study in Nature Neuroscience was the first to show that a psychological and social experience, such as abuse, causes molecular-level changes in the brain. It leaves a kind of chemical mark on the brain. The mechanism by which this occurs is epigenetic.

This means that it doesn’t change the structure of the gene, but changes its functioning, correct?
That’s exactly right. The addition of methyl radicals (CH3) to a specific stretch of DNA alters the activity of a gene that’s important in regulating the stress response. In stressful situations, the adrenal gland releases cortisol, a potent hormone that has a systemic impact on the body. As soon as it’s secreted, it activates glucocorticoid receptors in a region of the brain called the hippocampus, triggering an inhibitory response. The hippocampus sends signals to the hypothalamus, which releases hormones that suppress adrenal cortisol production. We call it the hypothalamic-pituitary-adrenal axis, or HPA, and it’s an important structure in the regulation of stress. Our work has led us to hypothesize that this inhibitory mechanism is altered in the brains of people who suffered abuse in childhood. Abuse usually comes from parents—biological or adoptive—and caregivers. These people aren’t abusive all the time. They are normally abusive when they’re emotionally upset or under the influence of drugs. In our understanding, the child’s brain perceives that this environment is hostile and unpredictable and deals with the situation by increasing their alertness level.

Would cortisol production in these people easily get out of hand?
The addition of methyl radicals to this gene makes it less active and reduces the amount of glucocorticoid receptors in the hippocampus. This impairs the inhibition of the HPA axis. These people become more alert as a result of the brain adapting to an environment that’s hostile and unpredictable, in other words, one in which they don’t know when the abuse may occur. From a clinical point of view, such people are more anxious and hypervigilant. This molecular mechanism would explain the increased risk, especially when these people become depressed and begin to experience suicidal ideation.

Is there a difference in brain function between someone who commits suicide and someone who doesn’t go beyond ideation?
That’s the kind of question we’re trying to answer.

Does the abuse have to occur at any specific stage of childhood to generate this type of change in the stress response?
I suspect so, although it’s not yet known at what age. The brain is a so-called plastic organ, which means that it adapts according to experience. This capacity for learning and adaptation is greatest in the first two decades of life. Negative experiences that occur during this period tend to have a larger impact on the ability to deal with stress and adversity.

McGill University The researcher and his team at the Douglas Research CenterMcGill University

They are not determinant, but they increase the propensity.
In psychiatry, nothing is determinant. There are associations, which we try to explain by means of theoretical models. Negative life experiences do not determine that a person will commit suicide. Many people suffer trauma and become resilient. But the proportion of those who have lived through abusive situations is higher among people who die by suicide than among those who don’t commit the act or who die from other causes.

How are studies conducted to identify these connections?
To study these phenomena, it’s necessary to have access to brain tissue. These changes are specific to this tissue and looking in the blood is pointless. At McGill University, we have a bank with about 4,000 brains of people who died from suicide or other causes. In some cases, we follow them during a portion of their lives and collect the brain after death. In others, we have access to the brain first and do the detective work afterwards, interviewing husbands or wives, siblings and parents, to try to find out what their lives were like. We also have access to their medical history and records of drugs they used, and data from the national youth protection agency, which stores the histories of children who have lived in families with varying levels of dysfunction. And we conduct follow-up studies on groups representative of the general population. However, in these groups we investigate the behaviors and personality traits that increase the risk of suicide.

Are there traumas that increase the risk more than others?
We didnt find any data to support that conclusion. Our studies indicate that traumas are experiences that are much more subjective than objective. They depend on the way they are experienced. We found that the identity of the aggressor is an important moderating factor in the relationship between the history of abuse and suicide. Those who were abused by someone very close, such as a parent, are at greater risk of suicidal behavior than those who suffered abuse by a stranger.

What’s the explanation for that?
I believe that the psychological impact of the experience is greater in the first case. It may also have to do with repetition.

Suicide rates vary widely across the world. Why is that?
Men commit suicide more than women, especially men aged 35 to 65—the proportion can vary from two-to-one to five-to-one depending on the country. The exception is some Asian countries, notably China and India, where the rate was higher among women, but this is changing. In general, women attempt suicide more than men, but men use more lethal methods. Another reason that explains the higher proportion of men committing suicide in some countries is the abuse of alcohol and drugs. This is more common in the nations that were part of the former Soviet Union. Alcohol has a disinhibiting effect, which makes it easier for depressed people to put their thoughts of self-annihilation into practice. The rest of the statistics vary widely. Suicide rates are higher in Russia and Canada than in Brazil, but when we examine the data closely, it can be observed that these rates vary over time and between different regions of countries. This variability is explained by oscillations in social factors.

In the last few decades, it seems that there has been a global reduction in suicide rates. What’s behind that?
It has decreased in a large part of the world. One explanation for the decline is the improvement in the treatment of depression that’s occurred over the past 20 years. But there are exceptions. In the United States, South Korea, and Brazil suicides have increased. In the first, it’s possibly caused by increased access to firearms and, in South Korea, it’s associated with major changes in social structure, including family relationships. In Brazil, we still don’t quite understand what explains the variation.

What can be done to reduce these rates?
We will never completely eliminate the risk, but it is possible to reduce it. One way to achieve this is to reduce mistreatment and traumatic experiences early in life by adopting demographic intervention programs that identify families at risk and teach parenting skills. Another is to reduce the stigma around mental health problems, to facilitate their identification and treatment. It’s also important to hinder access to the methods, such as firearms and pesticides. A suicide crisis is often impulsive and transient.

Is there any evidence that pandemics–such as the current one—increase the occurrence of suicides?
There have been a few articles published on the subject, but so far nothing suggests that the current pandemic has caused an increase in the suicide rate, although some studies indicate an increase in suicidal ideation among certain population groups.

You were born in Argentina and studied in Brazil. What was your time here like?
I’ve been highly influenced by my years in Brazil. My mother is Brazilian. I moved to the country when I was ten years old. I studied at the São Paulo State School of Medicine, where I acquired a culture of inquisitiveness and respect for the value of research. I interacted very closely with two phenomenal people, psychiatrist Jair Mari and geneticist Marília Cardoso Smith, who had a great influence on my personal and scientific education. Today I am head of the psychiatry department at a well-known university and scientific director of an important research center. There may be more financial resources, equipment, and autonomy for research here, but the academic and scientific training offered by UNIFESP is second to none.