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Identifying genetic and exposure risk factors is key for understanding chronic posttraumatic stress disorder (PTSD). This study found polygenic risk and trauma severity predict long-term PTSD trajectories in World Trade Center responders.

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Area of Science:

  • Psychiatry and Genetics
  • Trauma Research

Background:

  • Posttraumatic stress disorder (PTSD) can persist long-term, making identification of chronic risk factors essential for clinical research.
  • Trauma exposure severity and polygenic liability are known predictors of PTSD onset and severity, but their long-term impact is less understood.

Purpose of the Study:

  • To investigate whether trauma exposure severity and polygenic risk for PTSD symptoms independently predict long-term PTSD symptom trajectories.
  • To analyze 20-year PTSD trajectories in World Trade Center responders.

Main Methods:

  • Prospective longitudinal cohort study with 49,402 observations from 5,687 World Trade Center responders (2002-2022).
  • Determined best-fitting model for 20-year PTSD trajectories.
  • Included polygenic risk score and traumatic exposure sum score as predictors of initial PTSD levels and rates of change, adjusting for covariates.

Main Results:

  • Polygenic risk score significantly predicted rates of change in PTSD symptoms, indicating higher risk associated with steeper, arch-shaped trajectories.
  • Trauma exposure severity predicted both initial PTSD symptom levels and rates of change, with a stronger effect on initial levels.
  • Findings were independent of initial PTSD symptom levels (intercept).

Conclusions:

  • Polygenic liability and trauma exposure severity are significant predictors of long-term PTSD prognosis.
  • These factors can inform future clinical studies and risk stratification in trauma-exposed populations.