Genetic vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohorts

eClinicalMedicine, 2024 · DOI: https://doi.org/10.1016/j.eclinm.2024.102956 · Published: December 1, 2024

Simple Explanation

This study investigates the genetic factors that contribute to PTSD and depression after a mild traumatic brain injury (mTBI). Researchers used polygenic risk scores (PRS) for PTSD and major depressive disorder (MDD) to see if they were linked to the development of these conditions after mTBI. The study found that the PTSD-PRS was associated with a higher likelihood of developing PTSD after mTBI. Although the MDD-PRS increased the risk of depression after mTBI, this was less consistent than the PTSD findings. The research suggests that there is a shared genetic vulnerability for adverse psychological health outcomes after mTBI, meaning that genes influencing PTSD can also influence depression, and vice versa. These genetic scores could potentially be used to improve risk prediction and select participants for intervention trials.

Study Duration

CENTER-TBI: December 2014 – December 2017; TRACK-TBI: March 2014 – July 2018

Participants

1869 patients with mTBI (1143 from CENTER-TBI, 726 from TRACK-TBI)

Evidence Level

Not specified

Key Findings

1
PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p < 0.001].
2
MDD-PRS increased the risk of depression after TBI, with a pooled OR of 1.26 [95% CI 1.03–1.53, p = 0.02].
3
Patients in the highest cognate PRS quintile had increased odds of 3.16 [95% CI 1.80–5.55] and 2.03 [95% CI 1.04–3.94] of developing PTSD or depression compared to the lowest quintile, respectively.

Research Summary

This meta-analysis used data from the CENTER-TBI and TRACK-TBI studies to explore whether polygenic risk scores (PRS) for PTSD and major depressive disorder (MDD) are associated with the development of PTSD and depression after mild traumatic brain injury (mTBI). The study found that PTSD-PRS was significantly associated with an increased risk of PTSD after mTBI, while MDD-PRS showed a less robust but still significant association with depression after mTBI. These associations suggest a shared genetic vulnerability for adverse psychological outcomes following TBI. The researchers conclude that genetic predisposition plays a role in the development of psychopathology after TBI and that incorporating PRSs could improve risk prediction and identify enriched populations for therapeutic interventions.

Practical Implications

Improved Risk Prediction

Polygenic risk scores could improve the prediction of individual risk for PTSD and depression following TBI, aiding in prognostication.

Enrichment for Interventional Trials

PRSs could be used to enrich populations for trials of existing or new therapies, focusing on individuals with a higher genetic predisposition.

Personalized Treatment Approaches

Understanding the genetic component of mental health outcomes after TBI may allow for more rational approaches to identifying, testing, and using therapeutic interventions.

Study Limitations

1
The study population was primarily recruited from large trauma centers, constraining severity and case-mix.
2
Patients lost to six-month follow-up were excluded, leading to potential biases due to non-random missingness.
3
The instruments used to identify PTSD and depression (PCL-5 and PHQ-9) do not fully replicate the gold standard diagnosis resulting from a clinical interview.

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