Early Intervention Following Trauma May Mitigate Genetic Risk for PTSD in Civilians: A Pilot Prospective Emergency Department Study

Background: Civilian posttraumatic stress disorder (PTSD) and combat PTSD are major public health concerns. Although a number of psychosocial risk factors have been identified related to PTSD risk, there are no accepted, robust biological predictors that identify who will develop PTSD or who will respond to early intervention following trauma. We wished to examine whether genetic risk for PTSD can be mitigated with an early intervention.

Method: 65 emergency department patients recruited in 2009-2010 at Grady Memorial Hospital in Atlanta, Georgia, who met criterion A of DSM-IV PTSD received either 3 sessions of an exposure intervention, beginning in the emergency department shortly after trauma exposure or assessment only. PTSD symptoms were assessed 4 and 12 weeks after trauma exposure. A composite additive risk score was derived from polymorphisms in 10 previously identified genes associated with stress-response (ADCYAP1R1, COMT, CRHR1, DBH, DRD2, FAAH, FKBP5, NPY, NTRK2, and PCLO), and gene x treatment effects were examined. The intervention included 3 sessions of imaginal exposure to the trauma memory and additional exposure homework. The primary outcome measure was the PTSD Symptom Scale-Interview Version or DSM-IV-based PTSD diagnosis in patients related to genotype and treatment group.

Results: A gene x intervention x time effect was detected for individual polymorphisms, in particular the PACAP receptor, ADCYAP1R1, as well as with a combined genotype risk score created from independent SNP markers. Subjects who did not receive treatment had higher symptoms than those who received intervention. Furthermore, subjects with the “risk” genotypes who did not receive intervention had higher PTSD symptoms compared to those with the “low-risk” or “resilience” genotypes or those who received intervention. Additionally, PTSD symptoms correlated with level of genetic risk at week 12 (P < .005) in the assessment-only group, but with no relationship in the intervention group, even after controlling for age, sex, race, education, income, and childhood trauma. Using logistic regression, the number of risk alleles was significantly associated with likelihood of PTSD diagnosis at week 12 (P < .05).

Conclusions: This pilot prospective study suggests that combined genetic variants may serve to predict those most at risk for developing PTSD following trauma. A psychotherapeutic intervention initiated in the emergency department within hours of the trauma may mitigate this risk. The role of genetic predictors of risk and resilience should be further evaluated in larger, prospective intervention and prevention trials.

Trial Registration: ClinicalTrials.gov identifier: NCT00895518