Number of traumatic brain injuries and temporal associations with depression: A register-based cohort study.

Objective: To explore the association of the number of traumatic brain injuries (TBIs) and temporal associations with the subsequent risk of depression in the population.

Methods: National register-based cohort study on all individuals registered with TBI (ICD-10: S06, ICD-8: 85.0-85.5) from 1977 to 2015 in Denmark (n = 494,216) and a sex- and age-matched reference population (n = 499,505). The associations with the number of TBIs and time to depression (0-6, 7-12 and more than 12 months following TBI) were analyzed using Cox proportional hazard regression.

Results: During a follow-up of mean 14.5 (SD 11.3) years, a total of 27,873 (5.6%) individuals who had at least one TBI and 15,195 (3.0%) in the reference population were diagnosed with a depression. First-time TBI was associated with a higher risk of depression in both men (HR = 1.73 [95% CI:1.67-1.79]) and women (HR = 1.66 [95% CI:1.61-1.70]) after multiple adjustments for educational status and comorbidities including previous depression, and the association became stronger in a dose-response association with the number of TBIs (test for trend p < 0.01). The HRs for depression were highest the first 6 months after the TBI in both men (HR = 5.69 [95% CI:4.66-6.94]) and women (HR = 4.55 [95% CI:3.93-5.26]) and decreased gradually the following year but remained elevated from one year after TBI until end of follow-up independent of the number of TBIs (p < 0.01). The associations did not vary with age or calendar time.

Conclusion: Traumatic brain injury is associated with a higher risk of depression, especially in the first months after TBI and the risk increases with the number of TBIs.