Accelerated epigenetic aging predicts major depression and brain changes after trauma
Emergency department measurements of GrimAge and DunedinPACE biological aging markers tracked subsequent depressive symptoms and neural connectivity shifts in adults over 35.
In a study of 706 human trauma patients enrolled in emergency departments, researchers evaluated biological age acceleration shortly after injury. The team measured three epigenetic clocks—PhenoAge, GrimAge, and DunedinPACE—within 72 hours of trauma. Participants underwent functional MRI scans two weeks later and depression screenings after six months.
Out of 660 participants evaluated at six months, 160 screened positive for probable major depressive disorder. Faster biological aging assessed by GrimAge and DunedinPACE significantly increased the odds of depression, even after adjusting for prior trauma and disability. These associations occurred exclusively in participants aged 35 and older. PhenoAge showed no significant link. Additionally, DunedinPACE was significantly associated with altered functional connectivity across 14 brain network pairs among 217 imaged patients.
Why it matters
The findings suggest that molecular measures of biological aging can reflect individual susceptibility to trauma-induced psychiatric disorders. They also link systemic epigenetic aging markers directly to alterations in functional brain networks.
Caveats
This work is an observational preprint that has not yet completed peer review. Additionally, the neuroimaging findings were evaluated in a smaller subset of 217 participants.
- Trauma
- Epigenetic alterations
- DNA methylation
- Major depressive disorder
- DunedinPACE
- GrimAge
- PhenoAge
- Homo sapiens
The paper
Epigenetic age acceleration is associated with brain connectivity changes and the risk of major depression after trauma
Navarro-Flores A, Milla H, Linnstaedt SD et al.
medRxiv · 28 Sep 2026 · Preprint, not yet peer-reviewed