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

TL;DR

This study finds that genetic variations in CRHBP and FKBP5 genes, combined with childhood trauma, increase the risk of suicide attempts in patients with schizophrenia and bipolar disorder.

Contribution

The study identifies a gene-environment interaction between CRHBP, FKBP5, and childhood trauma in predicting suicide attempts in psychotic disorders.

Findings

The interaction of CRHBP and FKBP5 genes with childhood trauma increases suicide attempt risk (OR 4.17).

Emotional and sexual abuse show strong interactions with the genes, increasing suicide attempt risk (OR 3.67 and 3.32, respectively).

The study includes patients with schizophrenia and bipolar disorder, showing similar risk patterns across both conditions.

Abstract

Background/Objectives: 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 (CRHBP) and FK506-binding protein 5 (FKBP5) 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 CRHBP and FKBP5 genes and CT in the development of SA. Methods: 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 CRHBP (rs7728378, rs10474485, and rs1875999) and FKBP5 (rs3800373 and rs9296158) and CT in SA. Results: The analysis showed that the interaction of CRHBP and FKBP5 with CT increases the risk of presenting at least one SA (OR 4.17; 95% CI [2.67–6.52]; p < 0.0001). Additionally, we observed interaction with childhood abuse (OR 4.09; 95% CI [2.61–6.39]; p < 0.0001), mainly with emotional (OR 3.67; 95% CI [2.34–5.77]; p < 0.0001) and sexual abuse (OR 3.32; 95% CI [2.11–5.23]; p < 0.0001). Conclusions: Our research indicates that genetic variations in CRHBP and FKBP5 genes and a history of CT increase the probability of presenting at least one SA in patients with schizophrenia and bipolar disorder.

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