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Suicide is a puzzle. Fewer than 10% of people with depression attempt suicide, and about 10% of those who kill themselves were never diagnosed with any mental-health condition.

Now, a study is trying to determine what happens in the brain when a person attempts suicide, and what sets such people apart. The results could help researchers to understand whether suicide is driven by certain brain biology — and is not just a symptom of a recognized mental disorder.

The project, which launched this month, will recruit 50 people who have attempted suicide in the two weeks before enrolling in the study. Carlos Zarate, a psychiatrist at the US National Institute of Mental Health in Bethesda, Maryland, and his colleagues will compare these people's brain structure and function to that of 40 people who attempted suicide more than a year ago, 40 people with depression or anxiety who have never attempted suicide and a control group of 40 healthy people. In doing so, the researchers hope to elucidate the brain mechanisms associated with the impulse to kill oneself.

Zarate's team will also give ketamine, a psychoactive ‘party drug’, to the group that has recently attempted suicide. Ketamine, which is sometimes used to treat depression, can quickly arrest suicidal thoughts and behaviour — even in cases when it does not affect other symptoms of depression1. The effect is known to last for about a week.

To some researchers, such findings suggest that ketamine affects brain circuits that are specific to suicidal thinking. But John Mann, a psychiatrist at Columbia University in New York City, says that abnormal brain chemistry and genetics could also predispose a person to attempt suicide in times of great stress, such as after a job loss. “They’re part of the person, they're a trait,” Mann says. “They just get more important when the person gets ill.”

Written in the genes?

There is evidence that genetics influences a person’s suicide risk. For instance, biological relatives of adopted children who kill themselves are several times more likely to take their lives than the general population2.

Fabrice Jollant, a psychiatrist at McGill University in Montreal, Canada, suggests that this genetic influence is related to impulsivity and flawed judgement, rather than a specific mental illness. He has found that close relatives of people who killed themselves were more impulsive than a control group when playing a gambling game designed to test decision-making3. “It seems that this is something transmitted,” Jollant says.

Other researchers are seeking biomarkers that would allow clinicians to spot people most at risk of suicide. Alexander Niculescu, a psychiatrist at Indiana University in Indianapolis, and his colleagues have identified a set of six genes whose expression is altered in the blood of people who have killed themselves4. The team has found that combining these biomarkers with data from an app that tracks mood and risk factors can predict, with more than 90% accuracy, whether people with bipolar disorder or schizophrenia will eventually be hospitalized for a suicide attempt.4

And Mann is using positron emission tomography to track the best-studied biomarker, for the signalling molecule serotonin, in the brains of people who have attempted suicide5. Their altered serotonin patterns are similar to those seen after death in the brains of those who have killed themselves, says Mann.

Although serotonin levels are altered in people with depression, Mann has found differences between people who attempt suicide and those who are depressed but have no history of suicide attempts. He has also shown that serotonin levels are altered to a greater degree in those who make more serious suicide attempts — such as taking an entire bottle of painkillers — than in those whose attempts are less drastic6.

Ethical challenges

Researchers hope that a better understanding of the biology underlying suicide will lead to more effective treatments for suicidal impulses. But studies such as Zarate’s present difficult logistical and ethical challenges. Researchers must consider whether a person who has just attempted suicide can make informed decisions about whether to participate in research.

Michael Minzenberg, a psychiatrist at the University of California, San Francisco, knows these concerns all too well: he studies suicidal people with schizophrenia. Many of these people struggle with basic life skills, such as keeping a job or finding housing. “They’re a challenging group to treat, let alone to study,” Minzenberg says.

He and other researchers who study suicidal people say that they treat them with special care — and that the overall benefits of such studies outweigh any risks. “In most clinical trials, people at high risk of suicide are excluded, so we don’t know how to treat them,” Jollant says. “We need to assess this population, not just say ‘exclude them from trials’.”