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17 May 2013

Suicidal behaviour is a disease, psychiatrists argue

All lifelines pursued

As suicide rates climb steeply in the US a growing number of psychiatrists are arguing that suicidal behaviour should be considered as a disease in its own right, rather than as a behaviour resulting from a mood disorder.

They base their argument on mounting evidence showing that the brains of people who have committed suicide have striking similarities, quite distinct from what is seen in the brains of people who have similar mood disorders but who died of natural causes.

Suicide also tends to be more common in some families, suggesting there may be genetic and other biological factors in play. What’s more, most people with mood disorders never attempt to kill themselves, and about 10 per cent of suicides have no history of mental disease.

The idea of classifying suicidal tendencies as a disease is being taken seriously. The team behind the fifth edition of the Diagnostic Standards Manual (DSM-5) – the newest version of psychiatry’s “bible”, released at the American Psychiatric Association’s meeting in San Francisco this week – considered a proposal to have “suicide behaviour disorder” listed as a distinct diagnosis. It was ultimately put on probation: put into a list of topics deemed to require further research for possible inclusion in future DSM revisions.


Another argument for linking suicidal people together under a single diagnosis is that it could spur research into the neurological and genetic factors they have in common. This could allow psychiatrists to better predict someone’s suicide risk, and even lead to treatments that stop suicidal feelings.

Signs in the brain

Until the 1980s, the accepted view in psychiatry was that people who committed suicide were, by definition, depressed. But that view began to change when autopsies revealed distinctive features in the brains of people who had committed suicide, including structural changes in the prefrontal cortex – which controls high-level decision-making – and altered levels of the neurochemical serotonin. These characteristics appeared regardless of whether the people had suffered from depression, schizophrenia, bipolar disorder, or no disorder at all (Brain Research,

But there is no single neurological cause of suicide, says Gustavo Turecki of McGill University in Montreal. What is more likely, he says, is that environmental factors trigger a series of changes in the brains of people who are already genetically prone to suicide, contributing to a constellation of factors that ultimately increase risk. These factors include a history of abuse as a child, post-traumatic stress disorder, long periods of anxiety, or sleep deprivation.

The search for more of these factors is complicated by the rarity of brain samples from suicide victims and the lack of an animal model – humans are unique in their wilful ability to end their lives. But some studies are yielding insights. For example, when people with bipolar disorder who have previously attempted suicide begin taking lithium, they tend to stop attempting suicide even if the drug has no effect on their other symptoms. This suggests that the drug may be acting on neural pathways that specifically influence suicidal tendencies (Annual Review of Pharmacology and Toxicology, .

In the genes?

There is also growing evidence that genetics plays a role. For example, according to one study, identical twins share suicidal tendencies 15 per cent of the time, compared with 1 per cent in non-identical twins (Journal of Affective Disorders, And a study of adopted people who had committed suicide found that their biological relatives were six times more likely to commit suicide than members of the family that adopted them (American Journal of Medical Genetics,

A number of individual genes have been linked to suicide, such as those involved in the brain’s response to mood-lifting serotonin, and a signalling molecule called brain-derived neurotrophic factor (BDNF), which regulates the brain’s response to stress. Both tend to be suppressed in the brains of people who committed suicide, regardless of what mental disorder they had. Other studies of post-mortem brains have found that people who commit suicide after a bout of depression have different brain chemistry from depressed people who die of natural causes.

A study by Turecki, published this month, compared the brains of 46 people who had committed suicide with those of 16 people who died of natural causes. In the first group, 366 genes, mostly related to learning and memory, had a different set of epigenetic markers – chemical switches that turn genes on and off (American Journal of Psychiatry, The results are complicated by the fact that many of the people who committed suicide suffered from mental disorders, but Turecki says that suicide, rather than having a mental disorder, was the only significant predictor for these specific epigenetic changes.

No one yet knows the mechanism through which environmental factors would alter these genes, although stress hormones such as cortisol may be playing a role.

Understanding risk

Ultimately, biological and genetic markers might allow psychiatrists to better predict which patients are most at risk of suicide. But David Brent of the University of Pittsburgh, Pennsylvania, cautions that even if we can one day use biomarkers to predict if someone will make a suicide attempt, they do not tell us when. “If clinicians are keeping an eye on a patient, they need to know if there’s imminent risk,” he says.

However, knowing someone’s long-term suicide risk may have important implications for how a doctor chooses to treat that person, says Jan Fawcett of the University of New Mexico in Albuquerque.

For instance, a doctor may decide not to prescribe certain antidepressants to a patient with these biomarkers, as many drugs are thought to increase suicide risk. Another question would be whether to commit a person to a mental hospital – a major decision, he says, as people are most likely to commit suicide right after being released from hospital (Archives of General Psychiatry,

David Shaffer of Columbia University in New York, who was a member of the DSM-V working group, says that suicide behaviour disorder is “very much in the spirit” of the new Research Domain Criteria system that the US National Institute of Mental Health proposed as an alternative diagnosis standard to DSM-V. Rather than diagnosing people with depression or bipolar disorder, for example, the NIMH wants mental disorders to be diagnosed and treated more objectively using patients’ behaviour, genetics and neurobiology.

Ultimately, says Nader Perroud of the University of Geneva in Switzerland, if suicidal behaviour is considered as a disease in its own right, it will become possible to conduct more focused, evidence-based research on it and medications that treat it effectively. “We might be able to find a proper treatment for suicidal behaviour.”

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