Regulation of the HPA axis is affected by genetic factors. A recent study in two independent populations found that polymorphisms and haplotypes of the CRH type 1 receptor gene (CRHR1) (for example, a haplotype formed by three single-nucleotide polymorphisms (SNPs) in intron 1) moderate the influence of child abuse on depressive symptoms in adulthood, with certain alleles (rs7209436 and rs242940) and haplotypes exerting a protective effect42. Functional variants of the brain mineralocorticoid and glucocorticoid receptor (GR) genes, which are respectively involved in setting the threshold and regulating the termination of the HPA axis response to stress, have also been identified in humans25. For example, carriers of the N363S variant of the GR gene were shown to exhibit higher cortisol responses to the Trier Social Stress Test, a stress-inducing public speaking and mental arithmetic task43. Interestingly, four SNPs of FKBP5 (rs9296158, rs3800373, rs1360780 and rs9470080), a gene that codes for a `chaperone' protein that regulates GR sensitivity, were found to interact with the severity of childhood abuse in the prediction of PTSD symptoms in adults44. Another study demonstrated an association between
