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Closing In on a Suicide Gene

News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences

Dr. Willour

“Side effects of medications can overwhelm some patients,” says Willour. “Genetics is one way to get better options.”“

The newer tactics to find genes for psychiatric illnesses seem a bit like sitting at a microscope and flipping to a higher power lens. The searches are finer, more tailored. And like narrowing a ‘scope’s field, they focus on “pure” groups in the population, a move that may force a desired gene or genes into the open.

So this decade has had depression research, for example, that looks only at those who’ve suffered from an early onset of the illness, or a search for bipolar disorder (BP) genes that picks out people with psychosis as a symptom. Recently, the new mindset has brought us closer to confirming a genetic hand in suicide.

This year, a study by a Hopkins team and other collaborators linked a specific area of chromosome 2—section 2p11-12—to attempted suicide. What makes that exciting, says geneticist Virginia Willour, Ph.D., is that two earlier studies implicated the same site. “We’re all in the same place,” she told an online reporter. “And that’s pretty unusual. Sometimes you may be in the same ballpark, but these were right on top of each other. This is fantastic for those of us interested in finding genetic risk factors.”

The concurrence, along with the fact that the research was on patients with different psychiatric illnesses, suggests something important about suicidal behavior, that it’s in some ways independent of the usually accompanying disease. This fits in with the so-called two-hit idea that says people most likely to attempt suicide have both a psychiatric illness like BP, major depression or alcoholism and a second, independent risk factor. Possibly, that factor is what the studies are flushing out.

Willour’s team pulled data from an existing, whole-genome analysis of 162 families with bipolar disorder. They focused on differences in members of that group with positive answers to survey items about attempting suicide. One of the two earlier studies took a similar approach but looked at suicide attempters in families with major depression. The other focused on those in families with alcoholism.

And the nature of the independent factor, once it’s found? The geneticists suggest it may be tied to an increase in “impulsive aggression.”

Also, because a number of physiological studies suggest that suicide attempters are low in serotonin, it’s tempting to think that genes in that neurotransmitter’s pathways are involved. Willour cautions, however, about jumping the gun. “Just because we think a gene should be related to suicide doesn’t mean the body does.” Only finding the gene on chromosome 2 and tracing its function will tell.

That would be the next step.

Now Willour is pressing on to a far larger study—ultimately some 4,000 patient and control DNA samples. It could be powerful enough to pull the gene from an increasingly narrow field of candidates.

“Our goal,” she says, “is to identify patients at risk of attempting suicide. We also want treatments—medications—with a rationale based on the biology.”

Fall 2007 Index | Hopkins Newsletter Archive