Certain Proteins in Your Blood May Increase Suicide Risk

Suicide attempts are common, impulsive, one-time efforts that are not ever repeated and almost always not fatal – unless a gun is involved. Suicide fatality depends on the lethality of the method used; firearms are extremely lethal. The US has the highest prevalence of civilian-owned firearms than any other country in the world and the highest rates of suicide by firearm, usually by a handgun. In 2021 there were over 27,000 suicides by firearm: That’s about once every eight hours, every day! The irony is that most gun owners purchase their first firearm for personal protection. The study found an elevated risk of suicide among many of the first-time handgun owners. The risk of suicide by firearm peaked in the period immediately after their first handgun acquisition.

Firearms not only make it more likely that the suicide will succeed, but the risk of suicide is also three times as high when there is firearm access as when there is not. Another recent study tracked firearm ownership and mortality for more than a decade of over 26 million adults. In this study, handgun owners were slightly younger than nonowners, male (78.1%), white (74.7%), and living in a rural area. Given these population characteristics, it’s not surprising that males accounted for 70% of the suicides and 83% of the suicides by firearm.

There’s something unique about people who purchase handguns that also distinguishes them from others. The rate of suicide by any method among handgun male owners was three times as high as that among male nonowners. The corresponding rate among female handgun owners was seven times as high as that among female nonowners. Overall, the risk of suicide by firearm among female handgun owners was substantially greater than that among male handgun owners. Thus, handgun ownership may impose a particularly high risk of suicide for women because of the pairing of their higher propensity to attempt suicide with ready access to an extremely lethal method.

Can we predict who is at risk?

A recent large-scale genome-wide association studies meta-analysis, involving over 29,000 cases of suicide attempts or suicides, revealed the existence of some important blood and brain proteins that influence this complex behavior.

Proteins are the main functional component of cells and biological processes and the ultimate products of gene expression. Proteins in the brain play important roles in regulating brain function, mental disorders, and suicide. Blood proteins are easy to obtain and can provide useful information on various physiological and pathological processes. Integrating protein data from blood and brain can provide important insights into the underlying mechanisms of complex behaviors, such as suicide.

The Results: Three genes (GLRX5, GMPPB, and FUCA2) and the proteins they produce exhibited strong evidence of influencing suicide. GLRX5 encodes a mitochondrial protein that plays a critical role in maintaining normal iron homeostasis. Several studies have reported a close association between blood iron homeostasis and suicide risk as well as mental health. GLRX5 interacts with another protein that is the target of the psychiatric medication Clozapine, which was the first medication approved for preventing suicidal behavior.

GMPPB encodes a protein that is known to be dysfunctional in the brains of patients with major depressive disorder. In the current study, increased levels of this protein were significantly associated with a risk of suicide. This protein is also involved in the mechanism of action of the popular antidepressant drug Esketamine.

Finally, the FUCA2 gene encodes a protein that has been linked to a variety of neurological diseases, such as Parkinson’s disease and Alzheimer’s disease, as well as psychiatric disorders such as depression and suicide.

In conclusion, a group of comprehensive analyses provide compelling evidence supporting a causal association of three brain proteins with suicide. This information could be useful in the future to predict who is at risk of committing suicide by firearm, a method that is both extremely efficient and lethal.

If you or someone you love is contemplating suicide, seek help immediately. For help 24/7 dial 988 for the National Suicide Prevention Lifeline, or reach out to the Crisis Text Line by texting TALK to 741741. To find a therapist near you, visit the Psychology Today Therapy Directory.