Summary: New research shows that many people who die by suicide without prior suicidal thoughts or behaviors are not simply “missed cases”—they may have an entirely different underlying risk profile. Genetic analyses of more than 2,700 deaths revealed that these individuals carry fewer genetic risk factors for major psychiatric conditions compared to those with known suicidality.
This challenges long-held assumptions that better depression screening alone will catch most at-risk individuals. The findings point to overlooked biological and environmental pathways that current prevention strategies do not address.
Key Facts:
- A Distinct Risk Group: Individuals with no prior suicidality show fewer genetic risk factors for depression, anxiety, PTSD, and related traits.
- Not Hidden Depression: Their genetic profiles suggest they are not simply undiagnosed cases of typical psychiatric illness.
- New Prevention Needs: Conventional screening focused on mood disorders may miss this entire subgroup, requiring new approaches.
Source: University of Utah
Among friends and family of those who die by suicide, a common refrain is: I didn’t know.
While some people who die by suicide have prior attempts, about half of people who die by suicide have no documented suicidal thoughts or behaviors, nor do they have known psychiatric conditions associated with suicide risk, like depression. They have no previous clear indicators that they might be at risk at all.
A new genetic study at University of Utah found that people in this group of unexpected suicides aren’t just flying under the clinical radar via lower access to psychiatric services—their underlying risk factors may be fundamentally different.
The research found that people who die by suicide without prior non-fatal suicidal thoughts or behaviors have fewer psychiatric diagnoses and also fewer underlying genetic risk factors for psychiatric conditions compared to people who had shown these warning signs before dying by suicide.
“There are a lot of people out there who may be at risk of suicide where it’s not just that you’ve missed that they’re depressed, it’s likely that they’re in fact actually not depressed,” says Hilary Coon, PhD, professor of psychiatry in the Spencer Fox Eccles School of Medicine at the University of Utah and first author on the study.
“That is important in widening our view of who may be at risk. We need to start to think about aspects leading to risk in different ways.”
The results, published in JAMA Network Open, upend conventional beliefs about suicide risk and suggest new approaches to help save lives.
Uncovering hidden risk
Other research had shown that people who die by suicide without prior known suicidality are less likely to have psychiatric diagnoses, such as depression, compared to people with documented suicidal thoughts or behaviors.
But nobody knew the root cause of this difference. Maybe, researchers thought, people without known suicidality are still just as depressed or anxious—they’re just undiagnosed.
But Coon’s team was surprised to find that this isn’t the case. Instead, they found that this group has different genetic risk factors from people with known suicidality.
By comprehensively analyzing anonymized genetic data from more than 2,700 people who died by suicide, the researchers found that people without prior suicidality tend to have fewer genetic risk factors for several psychiatric conditions, including major depressive disorder, anxiety, Alzheimer’s disease, and PTSD.
The genetic data also suggests that this group isn’t any more likely than the general population to have milder conditions, like depressed mood and neuroticism.
This means that conventional wisdom on how to reduce suicide may need to be rethought.
“A tenet in suicide prevention has been that we just need to screen people better for associated conditions like depression,” Coon explains.
“And if people had the same sort of underlying vulnerabilities, then additional efforts in screening might be very helpful. But for those who actually have different underlying vulnerabilities, then increasing that screening might not help for them.”
Helping those most at risk for suicide
Figuring out how to find and treat these “hidden” at-risk individuals is a major focus of Coon’s upcoming research. Previous studies with clinical data have shown potential links between suicide risk and hard-to-treat conditions like chronic pain.
Coon is also investigating how other physical disorders, such as inflammation and respiratory conditions, may impact suicide risk. Her work will also focus on traits that may confer resilience to suicide.
Coon emphasizes that, on their own, individual genetic risk factors related to suicide have very small effects on risk, and there’s no single gene—or combination of genes—that causes suicide. Environmental and societal contexts are crucial contributors to risk, and understanding the interplay between the environment and underlying biology will be essential to discovering who’s at risk.
“We hope our work will begin to define subsets of individuals at risk, and also the contexts in which these risk characteristics may be important,” Coon says.
“If people have a certain type of clinical diagnosis that makes them particularly vulnerable within particular environmental contexts, they still may not ever say they’re suicidal. We hope our work may help reveal traits and contexts associated with high risk so that doctors can deliver care more effectively and specifically. ”
Better identification of at-risk individuals will help people get the care they need.
Do you need help?
Call 988 to reach a free, confidential 24/7 support line for suicidal crisis or emotional distress.
The Huntsman Mental Health Institute Crisis Care Center also offers 24/7 walk-in mental health services for adults. Additional information and assistance can be found through the Utah Chapter of the American Foundation for Suicide Prevention.
Are you concerned about a loved one or friend? Asking is the single most effective intervention for suicide.
Funding:
The work was supported by the National Institute of Mental Health (grants R01MH122412, R01MH123489, R01ES032028, and R01MH123619), Janssen Research & Development, the American Foundation for Suicide Prevention (grant BSG-1-005-18), the Brain & Behavior Research Foundation–National Alliance for Research on Schizophrenia and Depression (grants 28132, 28686, and 31249), and the Clark Tanner Foundation. Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Key Questions Answered:
A: They appear to have fundamentally different genetic and clinical profiles from those with known suicidality.
A: They show fewer genetic risk factors for depression, anxiety, PTSD, Alzheimer’s disease, and related conditions.
A: It suggests current screening methods overlook a distinct pathway to suicide, requiring new prevention strategies.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and mental health research news
Author: Sophia Friesen
Source: University of Utah
Contact: Sophia Friesen – University of Utah
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Genetic Liabilities to Neuropsychiatric Conditions in Suicide Deaths With No Prior Suicidality” by Hilary Coon et al. JAMA Network Open
Abstract
Genetic Liabilities to Neuropsychiatric Conditions in Suicide Deaths With No Prior Suicidality
Importance
Although suicide attempt is the most robust estimator of suicide death, few individuals who attempt it go on to die by suicide (<10%), and approximately 50% of suicide deaths occur in the absence of evidence of prior attempts. The risks are particularly poorly understood in this group.
Objective
To study underlying polygenic liabilities among suicide deaths without evidence of prior nonfatal suicidality (SD-N) compared with suicide deaths with prior suicidality (SD-S), testing prior results showing significantly lower clinical risks of neuropsychiatric traits in SD-N vs SD-S.
Design, Setting, and Participants
In this cohort study, polygenic scores (PGS) were computed using summary statistics from 12 published source studies, then compared across SD-N and SD-S groups taken from the Utah Suicide Mortality Research Study (cases accrued between December 1998 and October 2022). PGS from the suicide death cohorts were also compared to unselected population controls. Evidence of prior suicidality was determined from diagnoses and clinical notes.
Main Outcomes and Measures
Cohort differences in PGS reflecting neuropsychiatric conditions were tested using analysis of covariance, adjusting for sex, age, and genetic ancestry, followed by additional analyses within sex and within subgroups defined by age at death (50 years or younger vs older than 50 years). PGS spanned 12 neuropsychiatric conditions. Data were analyzed between July 2024 and July 2025.
Results
The SD-N cohort (n = 1337) had significantly more male suicide deaths (1105 [82.65%] vs 974 [67.95%]), with an older mean (SD) age at death (47.5 [18.9] vs 41.4 [15.6] years) than the SD-S cohort (n = 1432). The control cohort (n = 19 499) had significantly fewer males (8597 [44.09%]) than both suicide death subsets. Genetic ancestry was similar across the SD-N and SD-S groups (96.77% and 96.81% European ancestry), and control (97.38% European ancestry) groups.
Socioeconomic status was not significantly different across suicide cohorts adjusted for age and sex (occupation ranking SD-N mean [SD], 57.16 [24.54]; SD-S mean [SD], 54.72 [25.29]; t = 1.30; P = .70; maximum education SD-N mean [SD], 2.70 [1.12]; SD-S mean [SD], 2.67 [1.13]; Fisher exact test P = .38).
Comparing SD-N to SD-S revealed significantly lower (false discovery rate P < .05) PGS in the SD-N group for major depressive disorder (adjusted mean difference, 0.085 [95% CI, 0.018-0.152]; P = .01), depressed affect (adjusted mean difference, 0.081 [95% CI, 0.012-0.149]; P = .02), anxiety (adjusted mean difference, 0.091 [95% CI, 0.021-0.161]; P = .01), neuroticism (adjusted mean difference, 0.102 [95% CI, 0.033-0.171]; P = .004), and Alzheimer disease (adjusted mean difference, 0.090 [95% CI, 0.021-0.1658]; P = .01), and lower (false discovery rate P < .10) PGS in SD-N for posttraumatic stress disorder (adjusted mean difference, 0.070 [95% CI, 0.001-0.139]; P = .04). Of note, SD-N PGS were not significantly different from controls for depressed affect (adjusted mean difference, 0.037 [95% CI, −0.019 to 0.093]), neuroticism (adjusted mean difference, −0.001 [95% CI, −0.057 to 0.055]), or Alzheimer disease (adjusted mean difference, −0.027 [95% CI, −0.083 to 0.029]).
Conclusions and Relevance
In this cohort study, SD-N showed significantly different genetic liabilities to neuropsychiatric conditions from SD-S. Results have implications for future suicide research and prevention for persons at risk of mortality.
