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Related Experiment Video

Updated: Sep 16, 2025

Development of an Uncomplicated Mild Traumatic Brain Injury Model Modified by Weight-Drop Method and Evidenced by Magnetic Resonance Imaging
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Development of an Uncomplicated Mild Traumatic Brain Injury Model Modified by Weight-Drop Method and Evidenced by Magnetic Resonance Imaging

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Causal Relationship Between Depression and Traumatic Brain Injury: A Two-Sample Mendelian Randomization Analysis.

Shiping Wang1, Lei Pan2,3, Binyang Wang1,4

  • 1Department of Rehabilitation Medicine, The Affiliated Hospital of Yunnan University, Kunming, Yunnan Province, China.

Brain and Behavior
|July 7, 2025
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Summary

This study found that depression increases the risk of traumatic brain injury (TBI), and TBI, in turn, increases the risk of depression. These findings highlight the bidirectional causal relationship between these conditions.

Keywords:
TBIbidirectional MRcausal inferencedepressiongenetic instrumental variablespsychiatric comorbidity

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Traumatic brain injury (TBI) and depression represent significant global health challenges.
  • The precise causal link between TBI and depression remains incompletely understood.

Purpose of the Study:

  • To investigate the bidirectional causal relationship between depression and TBI.
  • To determine if depression is a risk factor for TBI and if TBI contributes to the development of depression.

Main Methods:

  • A two-sample Mendelian randomization (MR) analysis was employed using genome-wide association study (GWAS) summary statistics for depression (n=170,756) and TBI (n=3193).
  • Genetic variants significantly associated with depression and TBI were used as instrumental variables.
  • Inverse variance weighted (IVW) methods, MR-Egger regression, and MR-PRESSO were utilized to assess causality and address pleiotropy, with sensitivity analyses ensuring robustness.

Main Results:

  • Depression was found to significantly increase the risk of TBI (OR=1.137, P=0.022).
  • Conversely, TBI was also found to significantly increase the risk of depression (OR=1.083, P<0.001).
  • Sensitivity analyses confirmed the robustness of these bidirectional causal findings, with no significant evidence of heterogeneity or horizontal pleiotropy.

Conclusions:

  • The study provides robust evidence for a bidirectional causal relationship between depression and TBI.
  • Depression acts as a risk factor for TBI, and TBI subsequently elevates the risk for depression.
  • Integrated clinical monitoring is recommended for individuals affected by either condition.