Depression is both a risk factor for and outcome from traumatic brain injury in UK Biobank (N = 502,356)

J Affect Disord. 2026 Aug 1:406:121629. doi: 10.1016/j.jad.2026.121629. Epub 2026 Mar 13.

Abstract

Background: Traumatic brain injury (TBI) is a known risk factor for poorer later-life outcomes and earlier mortality, but its association with psychological health is less well-characterized. We tested for associations between TBI and depression, each ascertained multiple ways, and in opposing directions (depression predicting TBI; TBI predicting depression).

Methods: Using UK Biobank data (N = 502,356) we investigated bi-directional associations between TBI (ICD-10 coded broad- or narrow-band TBI) and depression (self-report and/or incident ICD-10 coded). We tested this in each direction: baseline historic TBI predicting the incidence of subsequent depression and, separately, baseline depression predicting the incidence of a first subsequent TBI. All analyses were adjusted for age at UK Biobank baseline assessment, sex, educational attainment, deprivation, smoking history, alcohol intake, physical and neurological health conditions.

Results: In participants with history of TBI (versus not), there was increased risk of subsequent incident depression, compared with participants with no documented TBI history (e.g. narrow-band TBI fully-adjusted hazard ratio [HR] = 2.18 risk of depression; 95% confidence interval [CI] = 1.87 to 2.55; P < 0.001). In the other direction there was evidence that people with history of lifetime depression had significantly increased risk of subsequent incident TBI (e.g. HR = 1.76 of narrow-band TBI, 95% CI = 1.61 to 1.94, P < 0.001).

Conclusion: We show significant associations between TBI and depression: depression was a risk factor for subsequent TBI in previously undiagnosed participants, but also vice-versa. Psychological support should be considered post-TBI, however clinical management should consider premorbid psychological health as a possible contributing factor.

MeSH terms

  • Adult
  • Aged
  • Biological Specimen Banks
  • Brain Injuries, Traumatic* / complications
  • Brain Injuries, Traumatic* / epidemiology
  • Brain Injuries, Traumatic* / psychology
  • Depression* / epidemiology
  • Depressive Disorder* / epidemiology
  • Depressive Disorder* / psychology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Risk Factors
  • UK Biobank
  • United Kingdom / epidemiology