W73. NR3C1 AND NR3C2 GENES INCREASED THE RISK OF SUICIDE ATTEMPT IN SUBJECTS WITH CHILDHOOD TRAUMA: AN ANALYSIS OF GENE EXPRESSION AND GXE INTERACTION

• Published in: European neuropsychopharmacology Vol. 75; pp. S142 - S143
• Main Authors: Sanabrais-Jiménez, Marco Antonio, Esquivel-López, Ayerim, Sotelo-Ramirez, Carlo Esteban, Ordoñez-Martínez, Bruno, Aguilar-García, Alejandro, Jiménez-Pavón, Joanna, Flores-Flores, Griselda, Camarena, Beatriz
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2023
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2023.08.260

Suicide behavior represents a worldwide public health problem. The glucocorticoid (NR3C1) and mineralocorticoid receptor (NR3C2) gene are important in the activation and modulation of the hypothalamic-pituitary-adrenal (HHA) axis, main regulator of the stress system. Childhood trauma (CT) is an environmental risk factor for develop a suicide attempt (SA) and has been associated with HPA axis dysregulation. Several studies have analyzed NR3C1 and NR3C2 in SA; however, the findings are not conclusive. Therefore, the aim of this study was to analyze gene expression and GxE interaction between NR3C1 and NR3C2 with CT in the development of SA. Gene expression analysis included 96 patients with psychiatric disorders (SA=69 and without SA=27) collected in the Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz. Assessment of CT was measured using the Childhood Trauma Questionnaire. NR3C1 and NR3C2 gene expression were analyzed by RT-qPCR with TaqMan probes. Statistical analyzes was performed with One-way ANOVA and Kruskal-Wallis test. GxE interaction analysis included 516 patients (SA=274 and without SA=242) using MDR program between NR3C1 (rs6198, rs6191, rs33388), NR3C2 (rs5522, rs2070951) genes and CT in SA. We observed overexpression (OE) of NR3C1 associated with high scores of physical abuse (p < 0.0001), sexual abuse (p=0.0006) and emotional negligence (p=0.014) in patients with SA. Also, we detected NR3C1 OE in subjects with and without SA that presented high physical negligence compared with subjects with low physical negligence with and without SA (p < 0.0001). In the total sample, we observed NR3C2 underexpression (UE) in subjects with high emotional (p < 0.0001), physical (p < 0.0001) and sexual abuse (p < 0.0001); and emotional (p < 0.0001) and physical negligence (p < 0.0001). In addition, we analyzed the effect of risk alleles to SA in the gene expression of NR3C1 and NR3C2 detecting differential levels of gene expression related with rs6198, rs6191 of NR3C1, and rs5522 of NR3C2. The analysis of the GxE interaction of the risk allele showed an increased in the prediction of SA (OR=2.76; 95% CI, 1.93-3.94; p < 0.0001). Additionally, we observed interaction in the analysis of trauma subtypes for negligence (OR=2.12; 95% CI, 1.45-3.11; p < 0.0001), emotional abuse (OR=2.13; 95% CI, 1.48-3.05; p < 0.0001), and sexual abuse (OR=2.38; 95% CI, 1.56-3.64; p < 0.0001). The findings in the present study suggest that subjects with SA with a history of CT showed changes in the NR3C1 and NR3C2 gene expression. Interestingly, the changes in the expression were related with the presence of risk allele of the genes analyzed. Finally, our results showed an interaction between NR3C1 and NR3C2 with CT increasing the risk of having at least one SA. In conclusion, our findings support the involvement of NR3C1 and NR3C2 in suicide behavior.