Post-traumatic stress disorder (PTSD) affects approximately 5–10% of all individuals and is more predominant in women (Breslau, 2001). Advances in treatment and prevention will require identifying biomarkers to aid early diagnosis and understanding the mechanisms underlying maladaptive responses to trauma.

To further genetically probe this association, we analyzed the PACAP (Adcyap1) gene and its receptor-PAC1 (Adcyap1r1). Only the Adcyap1r1 SNP (rs2267735) was found to be associated with PTSD diagnosis in women (again not in males) (Figure 1b). Although note that this SNP association was not replicated in a less traumatized cohort (Chang et al., 2012). At the epigenetic level, we also found that differential methylation of the Adcyap1r1 gene was associated with PTSD symptoms (Figure 1c). Given the approximately 2 : 1 sex-bias in PTSD prevalence, we find it exciting that the Adcyap1r1 SNP is within a predicted estrogen response element (ERE). Furthermore, in a postmortem sample, we found that females had differential cortical expression of Adcyap1r1 mRNA levels as a function of their genotype. Notably, a recent follow-up study finds that the same genetic risk is associated with higher acoustic startle in traumatized boys and girls before puberty, suggesting that the estrogen effect may be age-dependent (Jovanovic et al, 2012).

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD