A world-first study has shown that it is possible to determine who is likely to get depression in late-life based on a “genetic score.”
The longitudinal study of more than 12,000 people over 70 paves the way for the potential use of genetic testing by doctors to predict those at high risk of age-related depression, according to researchers from Australia’s Monash University.
Such testing could also help to inform interventions to protect against the mental health condition.
Generally, depression is influenced by genetic and environmental factors. But the extent to which genetic predisposition contributes to late-life depression as we age has until now remained “largely a mystery” despite its high prevalence in this age group, study author professor Paul Lacaze told Newsweek.
“Our original hypothesis was that genetics would have a minor or even negligible role in depression risk when people are at that age, because we figured it would be due to other things that happen in their life [environmental factors],” Lacaze explained.
“But to our surprise, we found that the genomic risk score still performs very well in people above the age of 70 and the genetic component of depression is still pretty meaningful at that age in terms of laying the foundation for that predisposition.”
Late-life depression is a leading cause of disability in older adults and is associated with significant economic burden, according to the National Institutes of Health.
The new study investigated the association between a polygenic score (PGS) and depression outcomes, including severity, trajectories of depression and antidepressant medication use.
A person’s polygenic score encapsulates thousands or even millions of different genetic variants into a single measure that may predict future disease—in this case, depression,—the team explained.
“Understanding the role that genetics plays in late-life depression could help enable more early recognition and intervention, potentially improving the outcomes of depression, detection of those at risk, management or even prevention of depression,” said Lacaze.
The researchers followed participants enrolled into the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial, over a period of 4.7 years. All participants were of European descent and had no history of diagnosed cardiovascular disease events, dementia or permanent physical disability at baseline.
Lacaze acknowledged that while their study was based on Europeans due to the data available, the diversity of data sets needs to be increased “urgently.”
The team found that the polygenic score was significantly associated with future depression and also the use of anti-depressants.
The score of participants in the study was identified via the number of single genetic variants known to be associated with depression. By adding these up, the researchers were able to associate these scores with depression risk.
“The unique thing about a genomic score is that you’re born with your genes, so it’s set for your whole life, whereas environmental and other factors change throughout your life,” Lacaze explained.
“And the reason why it might manifest at one stage of someone’s life and not at others, is complicated. But the way I think about it is that everyone has slightly higher and lower predisposition to different outcomes.
“Having a high predisposition doesn’t guarantee or determine that you’re going to get a certain disease, but it puts you in a higher risk group that you’re at higher likelihood of that thing happening.”
Lacaze acknowledged that for something like cancer—one of the other diseases they’ve been looking at the polygenic scores of—there is a more obvious use case for prediction, intervention and prevention.
But for depression, while their findings show it is possible, the team are still considering how it would be appropriate to conduct predictions, at what age and with what intention.
Lacaze also suggested testing could help with determining which people may respond better to certain antidepressants depending on their genes, or giving people the autonomy to be proactive in managing their psyche if they know they might be prone to depression.
“One of the most extreme scenarios is you could do the genomic risk prediction for depression in a newborn baby and that information will be known for the child’s whole life to the parents. It’s possible, technically, for us to do that today, but whether that’s a good idea or not… probably isn’t,” he said.
This question remains until adulthood, hence the researchers are trying to focus on the scenarios where “the genomic information gives true utility, like clinical utility, rather than doing it just because we can.”
Explaining the decision to look into age-related depression, Lacaze said: “The onset of a lot of diseases starts to happen after the age of 70. And there’s a huge growing burden on our societies and health systems because of the aging population. There’s also very high rates of loneliness and depression in older people.
“So any potential approach to address that growing burden is something that we should be looking at.”
Next, Lacaze and his team will continue to look into the broader question of nature versus nurture.
He mused: “How much do your genes versus environment contribute to disease as you’re aging? Where or when might the use of genomics improve care for older people and in general across the health system?”
Do you have a tip on a health story that Newsweek should be covering? Do you have a question about depression? Let us know via [email protected].
Reference
Yu, C., Bakshi, A., Agustini, B., Walker, A., Lin, T., Lotfaliany, M., Williams, L. J., McNeil, J. J., Wray, N. R., Berk, M., & Lacaze, P. (2025). Genomic risk prediction for depression in a large prospective study of older adults of European descent. Molecular Psychiatry. https://doi.org/10.1038/s41380-025-03145-3
The post Genetic Test Can Reveal Risk of Late-Life Depression appeared first on Newsweek.
