for involvement of CRH in stress-related disorders60, these observations position drugs that influence CRHR1 as strong therapeutic candidates for PTSD and related conditions. Whereas a placebo-controlled trial of a CRHR1 antagonist in 128 women with PTSD produced unimpressive results61, our findings (albeit predominantly in men) suggest that there are potential unfulfilled opportunities with CRHR1 antagonists for PTSD that should be further explored, taking into account individual variation in CRHR1 – including epigenetic variation62 – as a source of differential antagonist efficacy, in keeping with the march toward precision psychiatry63. Furthermore, our unexpected finding of a negative association between PTSD symptom severity and predicted CRHR1 expression in nucleus accumbens – which suggests that an agonist might be therapeutic – requires further investigation.
