Genetic Link To Attempted Suicide Identified: Findings Could Lead To New Avenues Of Treatment Research

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A study of thousands of people with bipolar disorder suggests that genetic risk factors may influence the decision to attempt suicide.

Johns Hopkins scientists, reporting in the journal Molecular Psychiatry, have identified a small region on chromosome 2 that is associated with increased risk for attempted suicide. This small region contains four genes, including the ACP1 gene, and the researchers found more than normal levels of the ACP1 protein in the brains of people who had committed suicide. This protein is thought to influence the same biological pathway as lithium, a medication known to reduce the rate of suicidal behavior.

The researchers say the findings could lead to better suicide prevention efforts by providing new directions for research and drug development.

"We have long believed that genes play a role in what makes the difference between thinking about suicide and actually doing it," says study leader Virginia L. Willour, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost three times as likely.

Willour and her colleagues were able to replicate their findings in another group of samples: This one comprised DNA from more than 3,000 people with bipolar disorder. By using only DNA from people with bipolar disorder, the researchers say they were able to control for mental illness and narrow in on what may cause one group to attempt suicide and another to control those urges.

Suicide is estimated to kill 1.4 percent of the U.S. population, and roughly 4.6 percent of the population has attempted suicide at least once, Willour says. Among people with bipolar disorder, 47 percent think about killing themselves while 25 percent actually try to do it, she says.

Willour says the next steps are to replicate these findings and to determine the exact biological mechanisms through which these genetic risk factors increase the risk for suicidal behavior.

"What's promising are the implications of this work for learning more about the biology of suicide and the medications used to treat patients who may be at risk," Willour says. "Not everyone with bipolar disorder can take lithium because of its side effects. If we could give them another option, that would be fantastic."

Notes:

The study was funded by grants from the National Institute of Mental Health and the American Foundation for Suicide Prevention.

Other Hopkins researchers who participated in the study are Fayaz Seifuddin, M.S.; Pamela B. Mahon, Ph.D.; Dubravka Jancic, Ph.D.; Mehdi Pirooznia, M.D., Ph.D.; Barbara Schweizer, R.N., B.S.; Fernando S. Goes, M.D.; Francis Mondimore, M.D.; Dean F. MacKinnon, M.D.; J. Raymond DePaulo Jr., M.D.; Peter P. Zandi, Ph.D.; and James B. Potash, M.D., M.P.H.

Source:
Stephanie Desmon
Johns Hopkins Medical Institutions

Funding For The Broad's Stanley Center For Psychiatric Research Extended By $50M Grant

Impressed by four years of remarkable progress - including pioneering discoveries of the first genes underlying schizophrenia - the Stanley Medical Research Institute (SMRI) has announced that it will make a $50 million gift to support the Broad Institute's Stanley Center for Psychiatric Research.

Launched in 2007 with a ten-year, $100 million grant from the SMRI, the Stanley Center brings together scientists from diverse fields to unlock the genetic mysteries of schizophrenia, bipolar disorder and other mental illnesses, and translate these findings into new treatments for patients. The newly announced grant will provide $10 million per year in funding for an additional five years, making the Stanley Center a fixture in the biomedical landscape for many years to come.

"The renewed support of the Stanley Medical Research Institute underscores the remarkable progress we have made in just a few short years in unraveling the genetics of psychiatric illnesses," said Edward Scolnick, director of the Stanley Center and a core faculty member of the Broad Institute. "I am deeply grateful for their sustained support, which has catalyzed our work in countless ways."

In the United States alone, more than 8 million people suffer from schizophrenia and bipolar disorder. These illnesses tend to run in families, suggesting that they are influenced by genetic factors. Researchers in the Stanley Center are working to unearth the genetic underpinnings of psychiatric disease to pave the way toward better treatment options for patients.

"We are thrilled by the remarkable results flowing from the Stanley Center, which are laying bare the biological roots of psychiatric illnesses," said Ted Stanley, founder of the SMRI. "We are delighted that we can help enable even further progress through our continued support."

Over the last five years, researchers around the world have developed new tools and methods that have the potential to dramatically change the field of psychiatric research. With new genetic methods, tools for studying the brain's circuitry, and ways to grow cells in culture that accurately mimic living cells in the brain, the Broad's Stanley Center researchers can now bring these remarkable tools to bear on schizophrenia and bipolar disorder, as well as other psychiatric illnesses.

"It's really a new world and it's just starting," said Scolnick. "All of this has happened in the last few years. What's different in the field now is it's no longer stuck. A few years ago, no matter what you wanted to do, you didn't have a way of approaching these illnesses experimentally. And now you do."

Already, the Broad's Stanley Center and its partner institutions have uncovered several genes that confer risk of bipolar disorder or schizophrenia and have even found that these two diseases share common risk genes. Additionally, the researchers have revealed important biological pathways - or chains of molecular events - tied to the development of schizophrenia, which could lead to better treatment approaches. The new funding from the SMRI will provide sustained support for this kind of transformative research through early 2022.

"The Stanley Center brings together scientists with different areas of expertise to work together toward a common goal: uncovering the molecular mechanisms of mental illness to bring about better treatment," said Eric S. Lander, director of the Broad Institute. "Genomic tools are accelerating the pace of discovery in psychiatric disease research and the additional support of the Stanley Medical Research Institute ensures that this progress will continue for many years to come."

Source:
Nicole Davis
Broad Institute of MIT and Harvard