Neuroticism and posttraumatic stress disorder: A Mendelian randomization analysis

Area of Science:

• Psychiatry
• Genetics
• Epidemiology

Background:

• Epidemiological studies suggest a link between neuroticism and posttraumatic stress disorder (PTSD).
• The specific components of neuroticism contributing to PTSD risk remain unclear.
• Understanding these components is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the causal relationship between neuroticism clusters (worry, depressed affect, sensitivity to environmental stress and adversity - SESA) and the development of PTSD.
• To explore potential mediating roles of other psychiatric disorders in the association between neuroticism and PTSD.

Main Methods:

• Mendelian randomization (MR) analyses were employed using genome-wide association study summary statistics.
• Univariable, multivariable, and mediation MR analyses were conducted to assess direct and indirect causal effects.
• Data included three neuroticism clusters, PTSD, and nine other psychiatric disorders.

Main Results:

• All three neuroticism clusters showed an association with PTSD in univariable MR.
• In multivariable MR, only the association between SESA and PTSD remained significant, suggesting a direct causal link.
• Mediation analyses indicated that panic disorder partially mediated the SESA-PTSD association, and anorexia nervosa partially mediated the depressed affect-PTSD association.

Conclusions:

• Sensitivity to environmental stress and adversity (SESA) is a significant direct causal factor in PTSD development.
• Depressed affect and worry may influence PTSD risk indirectly through other psychiatric conditions.
• These findings enhance our understanding of neuroticism's complex role in PTSD etiology.