Can Genetic Risk Scores Help Explain How People With Depression Respond to Antidepressants?
February 6, 2026
Antidepressants are a common treatment for major depressive disorder, but not everyone responds to the first medication they try. A recent CAN-BIND study examined whether genetic risk scores, which reflect a person’s inherited risk for certain psychiatric conditions, are linked to how well someone responds to antidepressant treatment.
What Are Genetic Risk Scores?
Every person’s DNA contains many small genetic differences. A polygenic risk score combines the effects of many of these differences to estimate a person’s inherited risk for a trait or condition, such as depression, post-traumatic stress disorder, schizophrenia, or personality traits like neuroticism. Understanding these scores can help researchers explore why some people respond more effectively to antidepressant treatments than others.
“…using PRSs [polygenic risk scoring] could be valuable in identifying MDD patients at risk for poor treatment response or the development of treatment-resistant depression.“
How the Study Worked
To investigate this, the CAN-BIND-1 team analyzed genetic risk scores in 148 adults with major depressive disorder who were treated with escitalopram, a commonly prescribed antidepressant that increases serotonin in the brain to improve mood and reduce depression symptoms. Participants were followed over 16 weeks. After eight weeks, those who did not respond to escitalopram received an additional medication, aripiprazole, while those who did respond continued with escitalopram. The researchers then calculated each person’s genetic risk scores for several psychiatric conditions and traits and examined how these scores were linked to changes in symptoms and remission rates.
What Did This Study Reveal?
The study suggested that genetic risk scores may help explain differences in how people respond to antidepressant treatment. By analyzing these scores, researchers identified patterns showing why some individuals improved more quickly or fully than others:
- Higher genetic risk scores for post-traumatic stress disorder (PTSD) were associated with less improvement in depressive symptoms after eight weeks of escitalopram.
- Higher genetic risk scores for major depressive disorder showed mixed patterns, with some individuals experiencing better symptom improvement and higher remission rates after continuing escitalopram through sixteen weeks.
- Higher genetic risk scores for schizophrenia and attention-deficit/hyperactivity disorder were associated with smaller improvements in symptoms over sixteen weeks.
These findings are preliminary and need to be confirmed in larger studies. However, they suggest that genetics may play a role in antidepressant response and could eventually help guide more personalized treatment approaches for people with depression.
Why This Matters
Currently, finding an effective antidepressant often involves trial and error, which can delay symptom improvement and increase the risk of side effects. If genetic risk scores are validated in larger studies, they could provide one piece of the puzzle in predicting which medications are more likely to work for an individual. When combined with clinical assessments and other biological markers, this approach could support more precise, personalized treatment strategies, helping people with depression respond to treatment more quickly and effectively.
Limitations to Consider
Although this study used a well-defined group of adults with major depressive disorder from the CAN-BIND-1 trial, it is important to consider several factors when interpreting the findings. The sample size was relatively small, and depression is a highly diverse condition, so additional clinical and biological factors could also influence treatment outcomes. Future research that combines genetic information with these other factors may help identify more specific subtypes of depression and enhance the predictive value of genetic risk scores.
“MDD is a highly heterogeneous disorder, and additional clinical characteristics could influence genetic and biological mechanisms. Future studies incorporating additional clinical risk factors and non-genetic biomarkers of treatment response could help define more homogeneous subtypes of depression, potentially enhancing the predictive utility of PRS [polygenic risk scores].”
Final Takeaway
While genetic risk scores are not yet ready for clinical use, this study provides early evidence that genetics may influence how people respond to antidepressants. With further research, combining genetic information with clinical and biological data could help guide more tailored and effective treatment decisions in depression care.
Citation: Magarbeh, L., Elsheikh, S. S. M., Islam, F., Marshe, V. S., Men, X., Tavakoli, E., Kronenbuerger, M., Kloiber, S., Frey, B. N., Milev, R., Soares, C. N., Parikh, S. V., Placenza, F., Hassel, S., Taylor, V. H., Leri, F., Blier, P., Uher, R., Farzan, F., … Müller, D. J. (2025). Polygenic Risk Score Analysis of Antidepressant Treatment Outcomes: A CAN-BIND-1 Study Report: Analyse des résultats du traitement antidépresseur à l’aide des scores de risque polygéniques : Rapport sur l’étude CAN-BIND-1. The Canadian Journal of Psychiatry, 70(7), 552–564. https://doi.org/10.1177/07067437251329073