Genetic Variants in Depressed People Raise Suicide Risk
Certain mutations increase the likelihood nearly fivefold, study finds

By Amanda Gardner
HealthDay Reporter

MONDAY, Feb. 1 (HealthDay News) — Researchers have identified five gene variants that raise the risk for suicide attempts in people suffering from depression.

For now, the research provides insight into what goes awry in people who have suicidal tendencies. In the future, researchers hope the findings will translate into effective drug treatments.

"The goal of this kind of research is to find mechanistic targets for new therapies," explained study author Martin A. Kohli, a postdoctoral fellow at the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine. "It's a hint towards the search for new medications. We think we've discovered a new target for such kind of medication."

Kohli conducted the research while at the Max Planck Institute of Psychiatry in Munich, Germany. The study, published online Feb. 1, will appear in the April print issue of the Archives of General Psychiatry.

According to background information in the paper, 10 million to 20 million suicide attempts occur annually around the world. One million complete the act.

Previous research has indicated that reduced neurotrophic activity may be involved in major depressive disorder and suicidal behavior. Neurotrophins are proteins that keep neurons — specialized cells in the nervous system — alive and active.

"There is a lot of data from a lot of different sources that say that something is wrong with the neurotrophin system in people that develop [a tendency toward] suicide," confirmed Keith Young, vice chair of research psychiatry and behavioral science at Texas A&M Health Science Center College of Medicine, in Temple.

The researchers zeroed in on two genes because postmortem brain studies had shown reduced levels of these genes in suicide victims.

For the first phase of the study, the researchers collected blood samples from 394 depressed patients, 113 of whom had attempted suicide, then compared them with 366 healthy individuals.

These findings were then replicated in a group of 744 German patients with major depressive disorder, 152 of whom had tried suicide, and 921 black patients without a psychiatric diagnosis, 119 of whom had attempted suicide.

Five variants were more common in patients who had attempted suicide, the researchers found. People with three of the most significant mutations had almost a fivefold increased risk of a suicide attempt, they discovered.

"We can say that people who have this certain genotype have an elevated risk to try to commit suicide when they are depressed," Kohli said. The dysfunctional neurotrophic signaling was specific to suicide, not to depression, the authors noted.

Although the study authors did not look specifically at the function of these genes, previous research indicates that they "seem to be very important for neural biology," Kohli said. "They keep neurons alive or promote growth of neurons or remodulate the connectivity between them."

One expert noted that any insight into what raises the risk for suicide is welcomed.

"Suicide is a pretty intransigent problem. It's a very difficult, complex behavior that, despite many years of study, we have to acknowledge that suicide rates haven't changed a great deal," said Dr. Yeates Conwell, co-director of the Center for the Study and Prevention of Suicide at the University of Rochester Medical Center in New York. "We have a long way to go to understand the mechanisms of suicide, so this kind of work is very hopeful and findings like this that identify some significant associations between genetic patterns and a lifetime history of suicidal behavior are certainly intriguing and potentially important, [but] they have a long way to go to translate to suicide preventive interventions."

That said, Conwell added, the best way to look at suicide is in the interactions between genes and environment, and the variability in suicidality explained by genetic profiles is relatively small.

More information

Visit the American Foundation for Suicide Prevention for more on this topic.

SOURCES: Martin A. Kohli, Ph.D., postdoctoral fellow, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine; Keith Young, Ph.D., associate professor and vice chair, research psychiatry and behavioral science, Texas A&M Health Science Center College of Medicine, Temple, and neuroimaging and genetics core leader, VA Center of Excellence for Research on Returning War Veterans, Central Texas Veterans Health Care System; Yeates Conwell, M.D., professor, psychiatry, associate chair for academic affairs, and co-director, Center for the Study and Prevention of Suicide, University of Rochester Medical Center, New York; Feb. 1, 2010, Archives of General Psychiatry, online

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