Effect of CRHR1 and CRHR2 gene polymorphisms and childhood trauma in suicide attempt

Family, twin, and adoption studies have suggested that genetic factors might be involved in suicidal behavior. Corticotropin-releasing receptor type 1 (CRHR1) and 2 (CRHR2) genes play a key role in the activation and modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is considered a major stress regulator. Childhood trauma is an environmental risk factor associated with suicide attempt (SA) and it has been related to HPA axis dysregulation. This study aimed at analyzing the relationship of CRHR1 and CRHR2 genes with childhood trauma concerning the development of SA. In this study, we included 366 affective disorder patients. Among them, 183 patients had SA at least once and 183 had not SA. Information regarding SA and childhood trauma was obtained from medical records. Multifactor Dimensionality Reduction program was used to detect gene-environment interactions between CRHR1 (rs110402, rs242924, and rs16940665) and CRHR2 (rs2190242, rs2284217, and rs2014663) with childhood trauma in SA. The analysis showed an interaction of CRHR1 and CRHR2 with childhood trauma, thus conferring increased risk of having presented at least one SA (OR 7.44; 95% CI 4.58-12.07; p<0.0001). In addition, we observed the following in the trauma subtypes analysis: physical negligence (OR 4.72; 95% CI 3.01-7.40; p<0.0001), emotional abuse (OR 5.76; 95% CI 3.67-9.05; p<0.0001), and sexual abuse (OR 5.70; 95% CI 3.62-8.97; p<0.0001). Our results suggested that genetic variants of CRHR1 and CRHR2 genes in addition to physical negligence, and emotional and sexual abuse, contribute to increase risk of presented at least one SA.