Author: Doug M Dollemore
Suicide isn’t just about a bad day, week, month, or year. It’s not just about sadness or feeling hopeless. Nor is it just the predictable end result of schizophrenia, post-traumatic stress, or other mental disorders. In truth, death by suicide can be attributed to any or all of these things, plus a multitude of other factors that, in combination, can lead someone to end their own life.
Among the least understood of these factors is genetics. Research, much of it conducted at University of Utah Health, strongly suggests that risk for suicide death is partially inheritable and tracks in families independent of the effects of a shared environment. Identifying these genetic risk factors, scientists say, could lead to better ways to predict who might be at risk of suicide and new strategies for preventing the worst from happening.
“Understanding the underlying factors involved in suicidal behaviors is key,” says Eric Monson, M.D. Ph.D., a chief resident psychiatrist at U of U Health. “Suicide is inherently preventable, indicating that the more we know about its risks, the more potential lives that could be saved.”
To address this growing interest, University of Utah Health scientists are collaborating on an investigation called the Utah Suicide Genetic Risk Study (USGRS). The researchers, in cooperation with the state Office of the Medical Examiner, has collected nearly 8,000 DNA samples from Utahans who died by suicide, one of the largest DNA collections from suicide victims in the world.
This DNA resource is linked to the Utah Population Database (UPDB), which contains medical, demographic, and genealogic information, then de-identified for the research team. Together, these databases are helping U of U Health researchers identify specific gene variants, or SNPs (pronounced “snips”), and other genetic mutations that could contribute to suicide risk.
Among their latest findings are:
Variants in nerve signaling gene may play a role in risk of death by suicide
A pair of newly discovered variants in a gene that plays a key role in the transmission of nerve signals in the brain could help explain why death by suicide is more prevalent in some families, according to a study published in Molecular Psychiatry and led by U of U Health scientists.
Neurexin-1 (NRXN1) is a gene that helps regulate synapse activity in the brain. Synapses, also known as neuronal junctions, are where electronic signals pass from one nerve cell to another. In a previous genome-wide study of Utah families spanning several generations, NRXN1 was identified as a gene that could potentially elevate the risk of death by suicide. Other research suggests that NRXN1 is also associated with schizophrenia, autism, and other psychiatric disorders. These disorders may be linked to increased suicide risk.
In this new study, the researchers conducted laboratory experiments comparing the effects of normal NRXN1 to variant NRXN1. They discovered that NRXN1 variant synapses were twice as active as normal ones, suggesting that genetic alterations in this synapse pathway may play a role in increasing risk of suicide.
“This result gives us a clue about one of likely many gene pathways that may lead to increased risk,” says Hilary Coon, Ph.D., senior author of the study and a research professor in the Department of Psychiatry. “However, more study will be needed to understand how these changes might interact with environmental risk factors and additional genetic risks that are yet to be discovered.”
Prior trauma and a genetic predisposition for PTSD among those with bipolar disorder may increase risk of death by suicide
Individuals with bipolar disorder who are genetically predisposed to develop post-traumatic stress disorder following distressing events in their lives could be at greater risk of death by suicide than others who attempt it, according to a study in Translational Psychiatry led by U of U Heath scientists. The researchers say the finding could lead to better screening measures to detect prior trauma among bipolar disorder patients and identify those who are at greatest risk of suicide death.
The study, the largest combined clinical and genetic effort to investigate risk factors for death by suicide in bipolar disorder, is among the first to find differing risk factors for suicide attempts and death, according to Eric Monson, M.D., Ph.D., lead author of the study.
“Rates of death by suicide are 10 to 30 times higher for people with bipolar disorder than for the general population,” Monson says. “What we found in this study is that a combination of prior trauma, a genetic predisposition for PTSD, and a diagnosis of bipolar disorder is almost a perfect storm that puts an individual at greater risk of death by suicide.
Rare genetic variants could help scientist pinpoint genes linked to suicide risk
Five newly discovered rare but potent genetic variants could help scientists identify specific genes and genetic pathways associated with suicide death, according to a study published in the American Journal of Medical Genetics Part B. The study, led by Emily DiBlasi, Ph.D., a research instructor in the Department of Psychiatry, is among the first comprehensive examinations of rare genetic variations linked to suicide death.
Rare variants represent less than 1% of the genetic variations in humans. Unlike more common variants, which usually are found near or adjacent to generalized regions of the human genome, rare variants are found within specific genes. These variants can alter proteins and adversely affect how a gene functions; ultimately, they may have a powerful and damaging influence on the risk of death by suicide.
“Rare variants are a compelling source of the unaccounted genetic variation in suicide risk,” DiBlasi says. “Identifying these risk markers within specific genes could help us better understand some of the more puzzling aspects of the complex role that genetics might have in suicide death.”
However, while evidence for the role that genetics might play in suicidal behaviors is growing, DiBlasi and her U of U Health colleagues emphasize it shouldn’t be mistaken for destiny.
“We’re really in the early stages of genetic discovery,” DiBlasi says. “But based on what we know so far, it’s important to keep in mind that even if an individual has all of the variants that we’ve identified, it doesn’t mean they are going to die by suicide. It just means that their risk might, and I must stress might, be elevated.”
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