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

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). 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. 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). 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. • TBI is a relatively established risk factor for depression, but it is not clear to what extent depression predicts risk of TBI in the first instance. • The relationship between TBI and depression is to some extent bi-directional: in prospective longitudinal data, people with TBI are at higher risk of depression, but people with depression are at heightened risk of a subsequent TBI. • The cross-sectional association between TBI and depression is potentially overestimated to some extent by depression pre-dating TBI in some people. The relationship between TBI and mental health is complex, highlighting the importance of mental health screening and intervention in this population