Depression that strikes in youth may be biologically different from depression that arrives late in life. A genome-wide association study in Nature Genetics, co-led from Karolinska Institutet's Department of Medical Epidemiology and Biostatistics by corresponding authors Yi Lu and Alfonso Buil with lead author John R. Shorter, analysed medical records and genetic data from more than 150,000 people with depression and 360,000 controls across Denmark, Sweden, Norway, Finland and Estonia, within the Nordic TRYGGVE collaboration.
Comparing onset before age 25 with onset after 50, the researchers identified 12 genetic regions linked to early-onset depression but only 2 for late onset, and found the early form carries a stronger hereditary component. The clinical stakes are stark: about one in four people with high genetic risk for early-onset depression attempted suicide within ten years of diagnosis, roughly twice the rate observed among those with low genetic risk.
The findings suggest genetic information could eventually help identify young patients who need the most intensive follow-up, though translation into clinical practice will require careful validation and ethical groundwork. The study drew funding from the European Research Council and the US National Institute of Mental Health, with collaborators including the University of Oslo, Copenhagen University Hospital and the University of Tartu.