The Interaction Between CRHBP and FKBP5 Genes and Childhood Trauma Increases the Risk of Suicide Attempt in Patients with Schizophrenia and Bipolar Disorder

<b>Background/Objectives</b>: Patients with psychotic disorders have a lifetime risk of suicide attempt (SA) of around 10 to 50%. Genetic variants in the corticotropin-releasing hormone-binding protein (<i>CRHBP</i>) and FK506-binding protein 5 (<i>FKBP5</i>) genes, which are implicated in the hypothalamic-pituitary-adrenal axis and childhood trauma (CT), are considered risk factors for SA. This study aimed to examine the interaction between the <i>CRHBP</i> and <i>FKBP5</i> genes and CT in the development of SA. <b>Methods</b>: We included 350 patients, 180 patients with schizophrenia and 170 with bipolar disorder. The patients were divided into two groups: 175 with a history of SA and 175 without, and a sample of 350 healthy controls was also included. The Multifactor Dimensionality Reduction program was used to identify G × E interactions between the <i>CRHBP</i> (rs7728378, rs10474485, and rs1875999) and <i>FKBP5</i> (rs3800373 and rs9296158) and CT in SA. <b>Results</b>: The analysis showed that the interaction of <i>CRHBP</i> and <i>FKBP5</i> with CT increases the risk of presenting at least one SA (OR 4.17; 95% CI [2.67-6.52]; <i>p</i> < 0.0001). Additionally, we observed interaction with childhood abuse (OR 4.09; 95% CI [2.61-6.39]; <i>p</i> < 0.0001), mainly with emotional (OR 3.67; 95% CI [2.34-5.77]; <i>p</i> < 0.0001) and sexual abuse (OR 3.32; 95% CI [2.11-5.23]; <i>p</i> < 0.0001). <b>Conclusions</b>: Our research indicates that genetic variations in <i>CRHBP</i> and <i>FKBP5</i> genes and a history of CT increase the probability of presenting at least one SA in patients with schizophrenia and bipolar disorder.