Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective...

Area of Science:

• Neuroendocrinology
• Molecular Psychiatry
• Trauma Research

Background:

• Biological correlates of posttraumatic stress disorder (PTSD) are typically studied post-trauma, leaving pre-trauma vulnerability factors largely unknown.
• Investigating pre-trauma biological markers can identify individuals at higher risk for developing PTSD.
• The glucocorticoid receptor (GR) pathway is a key regulator of the stress response and a potential target for PTSD research.

Purpose of the Study:

• To determine if glucocorticoid receptor (GR) pathway components assessed before military deployment predict the development of PTSD symptoms.
• To examine whether predeployment GR number, mRNA expression of GR target genes (FKBP5, GILZ, SGK1), plasma cortisol, and childhood trauma predict PTSD development.
• To explore the association of predeployment GR number and FKBP5 mRNA expression with genetic polymorphisms in GR and FKBP5 genes, and their interaction with childhood trauma.

Main Methods:

• A cohort of 448 male soldiers was assessed before and 6 months after combat deployment.
• Participants were categorized into PTSD or comparison groups post-deployment.
• Logistic regression analysis was used to predict PTSD symptom development based on predeployment GR pathway components, childhood trauma, and genetic factors.

Main Results:

• Predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with an increased risk of developing high PTSD symptoms.
• Childhood trauma also independently predicted the development of high PTSD symptoms.
• A significant interaction between GR haplotype BclI and childhood trauma was observed, influencing GR number.

Conclusions:

• Predeployment glucocorticoid receptor (GR) pathway components serve as significant vulnerability factors for the subsequent development of posttraumatic stress disorder (PTSD) symptoms.
• These findings highlight the potential for early biological markers to predict PTSD risk in military personnel.
• The interplay between genetic factors, early life stress, and the GR pathway may contribute to PTSD vulnerability.