Since 65–90% of total CRH is thought to be tightly bound to CRHBP (Behan et al., 1997), the effectiveness of CRH in stimulating ACTH to release cortisol might be influenced by variation in CRHBP expression. The binding of cortisol to the GR and the translocation of the GR into the nucleus resulting in altered expression of stress-response genes is moderated by a large molecular complex. Of the genes encoding these proteins, only FKBP5 has been shown to be associated with stress-related phenotypes (Binder et al., 2004). In an earlier study of this dataset we showed that the interaction between childhood trauma and FKBP5 haplotypes and SNPs influenced suicidal behavior (Roy et al., 2010). The current study shows that an additive effect between CRHBP and FKBP5 variation in the interaction with childhood trauma predicts risk for suicide attempt. Amongst individuals who had been exposed to high childhood trauma, carriers of either the CRHBP rs7728378 major homozygote or the FKBP5 rs3800373 major homozygote had suicide attempt rates of 0.31–0.35 respectively but this rate was almost double (0.58) in individuals who carried both
