Depression is a risk factor for traumatic brain injury: Evidence from the National Health and Nutrition Examination Survey and Mendelian randomization analysis.

Abstract

Purpose: Previous studies have suggested an increased risk of post-traumatic depression in patients with traumatic brain injury (TBI). However, the pre-injury depression status of some included TBI patients remains unclear. This study aimed to investigate whether pre-existing depression increases the risk of TBI occurrence, thereby reassessing the causal relationship between depression and TBI.

Methods: A cross-sectional analysis was conducted using the National Health and Nutrition Examination Survey database for the periods 2011-2012 and 2013-2014. Multivariate-adjusted logistic regression was employed to evaluate the association between depression and TBI. Additionally, Mendelian randomization analysis was performed to examine potential causality.

Results: Among 5773 eligible the National Health and Nutrition Examination Survey participants, a subset of TBI patients exhibited pre-injury depression. After adjusting for covariates, multivariate logistic regression revealed positive correlations between TBI risk and depression severity: moderate (log^OR = 0.67, 95% confidence interval (CI): 0.18-1.20; p = 0.015), moderate-to-severe (log^OR = 1.10, 95% CI: 0.62-1.20; p = 0.001), and severe depression (log^OR = 1.2, 95% CI: 0.32-2.10; p = 0.015). Mendelian randomization analysis further supported a causal link, with inverse-variance weighted estimates indicating that depression was associated with higher TBI incidence (odds ratio = 1.02, 95% CI: 1.00-1.03; p = 0.006). Sensitivity analyses confirmed the robustness of these findings.

Conclusion: The pre-existing depressive state in patients with TBI is a risk factor contributing to the occurrence of TBI. Preventive measures against TBI should be strengthened in depressive patients. Additionally, the impact of the pre-injury depression on the statistical analysis of neuropsychiatric complications following TBI warrants careful consideration.