CRHR1 is in a large LD block on chromosome 17, making it difficult to discern its association with PTSD apart from other genes in that LD block. In our previous study of intrusive re-experiencing symptoms in MVP, we supported CHRH1 as the gene with strongest association via a trans-ancestral meta-analysis16. We now provide additional biological evidence that CRHR1 may be causally related to PTSD. PrediXcan-S analyses pointed to increased expression of CRHR1 in amygdala, hippocampus (the structure with highest colocalization probability), frontal cortex and anterior cingulate, regions repeatedly implicated as structurally or functionally abnormal in PTSD2. These results must be replicated and extended to other brain regions such as ventromedial prefrontal cortex, shown to be integral to fear learning and extinction58, processes hypothesized to be central to PTSD onset and recovery, respectively2,59. In concert with strong preclinical and clinical priors 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
